Trial Outcomes & Findings for Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD) (NCT NCT03946449)
NCT ID: NCT03946449
Last Updated: 2025-10-15
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
16 participants
Primary outcome timeframe
Baseline, Week 24
Results posted on
2025-10-15
Participant Flow
All eligible subjects required a pre-dose biopsy completed as part of the study within the screening window. Participants consisted of male and female adult homozygous Z allele individuals (PiZZ; based on genotype completed at Screening or from a source verifiable document) alpha-1 antitrypsin patients.
Participant milestones
| Measure |
ARO-AAT 100 mg Cohort 1b
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Primary Study Period
STARTED
|
4
|
4
|
8
|
|
Primary Study Period
COMPLETED
|
4
|
4
|
8
|
|
Primary Study Period
NOT COMPLETED
|
0
|
0
|
0
|
|
Treatment Extension I
STARTED
|
4
|
4
|
7
|
|
Treatment Extension I
COMPLETED
|
4
|
4
|
7
|
|
Treatment Extension I
NOT COMPLETED
|
0
|
0
|
0
|
|
Treatment Extension II
STARTED
|
4
|
4
|
7
|
|
Treatment Extension II
COMPLETED
|
4
|
4
|
4
|
|
Treatment Extension II
NOT COMPLETED
|
0
|
0
|
3
|
Reasons for withdrawal
| Measure |
ARO-AAT 100 mg Cohort 1b
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Treatment Extension II
Rolled over to another study
|
0
|
0
|
2
|
|
Treatment Extension II
Withdrawal by Subject
|
0
|
0
|
1
|
Baseline Characteristics
Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)
Baseline characteristics by cohort
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
n=8 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.8 years
STANDARD_DEVIATION 10.01 • n=99 Participants
|
44.5 years
STANDARD_DEVIATION 17.00 • n=107 Participants
|
54.6 years
STANDARD_DEVIATION 13.68 • n=206 Participants
|
52.1 years
STANDARD_DEVIATION 14.92 • n=157 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=157 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
14 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
16 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race/Ethnicity, Customized
White
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
16 Participants
n=157 Participants
|
|
Insoluble Z-Alpha 1 Antitrypsin (Z-AAT)
|
35.9750 nmol/g
STANDARD_DEVIATION 16.51694 • n=99 Participants
|
33.2750 nmol/g
STANDARD_DEVIATION 53.31019 • n=107 Participants
|
37.4500 nmol/g
STANDARD_DEVIATION 27.73075 • n=206 Participants
|
36.0375 nmol/g
STANDARD_DEVIATION 31.38345 • n=157 Participants
|
|
Soluble Z-AAT
|
26.3500 nmol/g
STANDARD_DEVIATION 5.18813 • n=99 Participants
|
24.3000 nmol/g
STANDARD_DEVIATION 10.58899 • n=107 Participants
|
23.3125 nmol/g
STANDARD_DEVIATION 7.59914 • n=206 Participants
|
24.3188 nmol/g
STANDARD_DEVIATION 7.50984 • n=157 Participants
|
|
Total Z-AAT
|
62.3250 nmol/g
STANDARD_DEVIATION 15.81210 • n=99 Participants
|
57.5750 nmol/g
STANDARD_DEVIATION 59.65391 • n=107 Participants
|
60.7625 nmol/g
STANDARD_DEVIATION 34.04199 • n=206 Participants
|
60.3563 nmol/g
STANDARD_DEVIATION 36.13456 • n=157 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: Full Analysis Set: all participants who received at least one dose of study drug and had baseline and post-dose liver biopsy histology results available.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b
Total Liver Z-AAT
|
-83.07 percent change
Standard Deviation 5.830
|
-79.84 percent change
Standard Deviation 10.519
|
—
|
|
Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b
Insoluble Liver-ZAAT
|
-81.58 percent change
Standard Deviation 6.947
|
-12.91 percent change
Standard Deviation 131.702
|
—
|
|
Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 24: Cohorts 1/1b
Soluble Liver Z-AAT
|
-85.36 percent change
Standard Deviation 4.835
|
-88.18 percent change
Standard Deviation 5.718
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 48Population: Full Analysis Set: all participants who received at least one dose of study drug and had baseline and post-dose liver biopsy histology results available. Participants with an assessment at given time point.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=7 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 48: Cohort 2
Total Liver Z-AAT
|
-90.26 percent change
Standard Deviation 9.029
|
—
|
—
|
|
Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 48: Cohort 2
Insoluble Liver-ZAAT
|
-84.83 percent change
Standard Deviation 19.920
|
—
|
—
|
|
Percent Change From Baseline in Total Liver Z-AAT, Insoluble Liver-ZAAT, and Soluble Liver Z-AAT at Week 48: Cohort 2
Soluble Liver Z-AAT
|
-92.64 percent change
Standard Deviation 7.482
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 2, 4, 6, 16, 24Population: Full Analysis Set: all participants who received at least one dose of study drug and had baseline and post-dose liver biopsy histology results available.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b
Week 2
|
-69.12 percent change
Standard Deviation 12.381
|
-77.28 percent change
Standard Deviation 7.394
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b
Week 4
|
-80.24 percent change
Standard Deviation 8.880
|
-88.07 percent change
Standard Deviation 4.931
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b
Week 6
|
-87.27 percent change
Standard Deviation 6.140
|
-91.79 percent change
Standard Deviation 3.795
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b
Week 16
|
-78.61 percent change
Standard Deviation 9.186
|
-83.08 percent change
Standard Deviation 6.269
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohorts 1/1b
Week 24
|
-83.85 percent change
Standard Deviation 5.426
|
-89.47 percent change
Standard Deviation 3.738
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 2, 4, 6, 16, 22, 28, 34, 40, 48Population: Full Analysis Set: all participants who received at least one dose of study drug and had baseline and post-dose liver biopsy histology results available.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 2
|
-72.08 percent change
Standard Deviation 8.645
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 4
|
-82.22 percent change
Standard Deviation 7.476
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 6
|
-89.92 percent change
Standard Deviation 4.024
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 16
|
-85.76 percent change
Standard Deviation 6.106
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 22
|
-90.87 percent change
Standard Deviation 4.246
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 28
|
-85.06 percent change
Standard Deviation 7.847
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 34
|
-89.54 percent change
Standard Deviation 5.434
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 40
|
-84.12 percent change
Standard Deviation 12.433
|
—
|
—
|
|
Percent Change From Baseline in Serum Z-AAT Over Time: Cohort 2
Week 48
|
-89.58 percent change
Standard Deviation 5.419
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2, Week 2, Week 4, Week 4 (24-48h post dose), Week 6, Week 16, Week 16 (24/48h post dose), Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at given time point.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Baseline (Day 1)
|
58.5 U/L
Standard Deviation 41.36
|
87.8 U/L
Standard Deviation 30.42
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Day 2 (24-48 hr post-dose)
|
58.5 U/L
Standard Deviation 42.68
|
88.3 U/L
Standard Deviation 32.72
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Week 2
|
76.5 U/L
Standard Deviation 55.24
|
99.8 U/L
Standard Deviation 53.89
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Week 4
|
62.3 U/L
Standard Deviation 35.77
|
106.5 U/L
Standard Deviation 42.57
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Week 4 (24-48 hr post-dose)
|
60.3 U/L
Standard Deviation 33.97
|
99.0 U/L
Standard Deviation 38.58
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Week 6
|
49.8 U/L
Standard Deviation 25.16
|
77.0 U/L
Standard Deviation 20.85
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Week 16
|
35.7 U/L
Standard Deviation 8.50
|
49.8 U/L
Standard Deviation 5.25
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Week 16 (24-48 hr post-dose)
|
31.5 U/L
Standard Deviation 8.85
|
42.7 U/L
Standard Deviation 3.06
|
—
|
|
Alanine Aminotransferase (ALT) Values Over Time: Cohorts 1/1b
Week 24
|
27.8 U/L
Standard Deviation 9.29
|
39.5 U/L
Standard Deviation 3.11
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2, Week 2, Week 4, Week 4 (24-48h post dose), Week 6, Week 16, Week 16 (24/48h post dose), Week 22, Week 28, Week 34, Week 40, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at given time point.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
ALT Values Over Time: Cohort 2
Baseline (Day 1)
|
62.1 U/L
Standard Deviation 14.98
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Day 2 (24-48 hr post-dose)
|
58.6 U/L
Standard Deviation 15.59
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 2
|
61.9 U/L
Standard Deviation 20.17
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 4
|
55.3 U/L
Standard Deviation 14.09
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 4 (24-48 hr post-dose)
|
53.0 U/L
Standard Deviation 14.83
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 6
|
54.9 U/L
Standard Deviation 9.79
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 16
|
39.6 U/L
Standard Deviation 13.13
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 16 (24-48 hr post-dose)
|
37.5 U/L
Standard Deviation 11.61
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 22
|
41.0 U/L
Standard Deviation 14.58
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 28
|
36.7 U/L
Standard Deviation 15.76
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 34
|
39.4 U/L
Standard Deviation 11.13
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 40
|
33.4 U/L
Standard Deviation 10.08
|
—
|
—
|
|
ALT Values Over Time: Cohort 2
Week 48
|
34.5 U/L
Standard Deviation 10.54
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2, Week 2, Week 4, Week 4 (24-48h post dose), Week 6, Week 16, Week 16 (24/48h post dose), Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug; n=participants with an assessment at given time point. Participants with an assessment at given time point.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Baseline (Day 1)
|
70.8 U/L
Standard Deviation 35.30
|
244.8 U/L
Standard Deviation 355.68
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Day 2 (24-48 hr post-dose)
|
70.5 U/L
Standard Deviation 39.07
|
247.3 U/L
Standard Deviation 358.01
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Week 2
|
66.0 U/L
Standard Deviation 37.15
|
210.8 U/L
Standard Deviation 304.4
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Week 4
|
73.0 U/L
Standard Deviation 43.37
|
222.0 U/L
Standard Deviation 334.85
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Week 6
|
64.0 U/L
Standard Deviation 35.62
|
199.3 U/L
Standard Deviation 292.28
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Week 16
|
48.0 U/L
Standard Deviation 23.25
|
135.3 U/L
Standard Deviation 190.31
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Week 16 (24-48 hr post-dose)
|
48.0 U/L
Standard Deviation 22.38
|
161.7 U/L
Standard Deviation 212.17
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Week 24
|
52.3 U/L
Standard Deviation 28.31
|
112.0 U/L
Standard Deviation 156.92
|
—
|
|
Gamma Glutamyl Transferase (GGT) Values Over Time: Cohorts 1/1b
Week 4 (24-48 hr post-dose)
|
70.0 U/L
Standard Deviation 45.19
|
210.3 U/L
Standard Deviation 312.0
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2, Week 2, Week 4, Week 4 (24-48h post dose), Week 6, Week 16, Week 16 (24/48h post dose), Week 22, Week 28, Week 34, Week 40, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug; n=participants with an assessment at given time point. Participants with an assessment at given time point.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
GGT Values Over Time: Cohort 2
Day 2 (24-48 hr post-dose)
|
62.1 U/L
Standard Deviation 33.21
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 2
|
60.6 U/L
Standard Deviation 33.14
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 4
|
59.1 U/L
Standard Deviation 49.82
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 4 (24-48 hr post-dose)
|
57.6 U/L
Standard Deviation 46.91
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 6
|
58.0 U/L
Standard Deviation 36.21
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 16
|
49.1 U/L
Standard Deviation 36.84
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 16 (24-48 hr post-dose)
|
48.3 U/L
Standard Deviation 38.68
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 22
|
48.5 U/L
Standard Deviation 34.85
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 28
|
44.5 U/L
Standard Deviation 34.62
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 34
|
45.3 U/L
Standard Deviation 31.37
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 40
|
45.3 U/L
Standard Deviation 38.20
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Week 48
|
48.5 U/L
Standard Deviation 45.05
|
—
|
—
|
|
GGT Values Over Time: Cohort 2
Baseline (Day 1)
|
62.5 U/L
Standard Deviation 31.09
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at given time point.
The FIB 4 score evaluates the degree of fibrosis in patients suspected of or already diagnosed with hepatic fibrosis. FIB-4 is calculated as (Age (years) \* aspartate aminotransferase) / (platelets \* √(ALT)). The result provided from the above equation is interpreted according to 2 cut off values: FIB 4 \<1.45 indicates absence of cirrhosis (with a negative predictive value of 90% for advanced fibrosis); FIB 4 between 1.45 - 3.25 are deemed inconclusive; FIB 4 \>3.25 indicates cirrhosis (with a positive predictive value of 65% for advanced fibrosis).
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Baseline (Day 1)
|
1.425 numerical score
Standard Deviation 0.3613
|
1.583 numerical score
Standard Deviation 0.9085
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Day 2 (24-48 hr post-dose)
|
1.353 numerical score
Standard Deviation 0.2699
|
1.618 numerical score
Standard Deviation 0.9668
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Week 2
|
1.580 numerical score
Standard Deviation 0.5806
|
1.900 numerical score
Standard Deviation 1.3056
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Week 4
|
1.260 numerical score
Standard Deviation 0.3840
|
1.750 numerical score
Standard Deviation 1.3273
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Week 4 (24-48 hr post-dose)
|
1.333 numerical score
Standard Deviation 0.4194
|
1.760 numerical score
Standard Deviation 1.3867
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Week 6
|
1.355 numerical score
Standard Deviation 0.4612
|
2.013 numerical score
Standard Deviation 1.1073
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Week 16
|
1.257 numerical score
Standard Deviation 0.3326
|
1.605 numerical score
Standard Deviation 1.221
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Week 16 (24-48 hr post-dose)
|
1.227 numerical score
Standard Deviation 0.2230
|
1.940 numerical score
Standard Deviation 1.6210
|
—
|
|
Fibrosis-4 Index (FIB4) Score Values Over Time: Cohorts 1/1b
Week 24
|
1.265 numerical score
Standard Deviation 0.3196
|
1.688 numerical score
Standard Deviation 1.2563
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 22, Week 28, Week 28 + 1 day, Week 34, Week 40, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at given time point.
The FIB 4 score evaluates the degree of fibrosis in patients suspected of or already diagnosed with hepatic fibrosis. FIB-4 is calculated as (Age (years) \* aspartate aminotransferase) / (platelets \* √(ALT)). The result provided from the above equation is interpreted according to 2 cut off values: FIB 4 \<1.45 indicates absence of cirrhosis (with a negative predictive value of 90% for advanced fibrosis); FIB 4 between 1.45 - 3.25 are deemed inconclusive; FIB 4 \>3.25 indicates cirrhosis (with a positive predictive value of 65% for advanced fibrosis).
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
FIB4 Score Values Over Time: Cohort 2
Week 22
|
1.336 numerical score
Standard Deviation 0.6269
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 28
|
1.377 numerical score
Standard Deviation 0.7152
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 34
|
1.239 numerical score
Standard Deviation 0.7527
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Baseline (Day 1)
|
1.395 numerical score
Standard Deviation 0.6634
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Day 2 (24-48 hr post-dose)
|
1.543 numerical score
Standard Deviation 0.8209
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 2
|
1.383 numerical score
Standard Deviation 0.6358
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 4
|
1.420 numerical score
Standard Deviation 0.7054
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 4 (24-48 hr post-dose)
|
1.356 numerical score
Standard Deviation 0.6344
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 6
|
1.367 numerical score
Standard Deviation 0.6419
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 16
|
1.299 numerical score
Standard Deviation 0.5636
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 16 (24-48 hr post-dose)
|
1.271 numerical score
Standard Deviation 0.6521
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 40
|
1.319 numerical score
Standard Deviation 0.5782
|
—
|
—
|
|
FIB4 Score Values Over Time: Cohort 2
Week 48
|
1.502 numerical score
Standard Deviation 0.7680
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at given time point.
The APRI suggests the level of hepatic fibrosis and possible liver disease. APRI is calculated as 100\*(aspartate aminotransferase/40) / platelets. Scores indicate the following: \< 0.5 = fibrosis is ruled out; 0.5 - 0.7 = associated with some kind of liver damage; 0.7 - 1 = significant fibrosis; \> 1 = associated with cirrhosis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Baseline (Day 1)
|
0.485 numerical score
Standard Deviation 0.2249
|
0.745 numerical score
Standard Deviation 0.3877
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Day 2 (24-48 hr post-dose)
|
0.463 numerical score
Standard Deviation 0.2133
|
0.753 numerical score
Standard Deviation 0.3923
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Week 2
|
0.633 numerical score
Standard Deviation 0.3349
|
0.910 numerical score
Standard Deviation 0.5231
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Week 4
|
0.463 numerical score
Standard Deviation 0.2185
|
0.810 numerical score
Standard Deviation 0.4031
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Week 4 (24-48 hr post-dose)
|
0.468 numerical score
Standard Deviation 0.1921
|
0.785 numerical score
Standard Deviation 0.4171
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Week 6
|
0.433 numerical score
Standard Deviation 0.1688
|
0.918 numerical score
Standard Deviation 0.1834
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Week 16
|
0.343 numerical score
Standard Deviation 0.0404
|
0.555 numerical score
Standard Deviation 0.3008
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Week 16 (24-48 hr post-dose)
|
0.330 numerical score
Standard Deviation 0.0700
|
0.603 numerical score
Standard Deviation 0.4203
|
—
|
|
Aspartate Aminotransferase-to-platelet Ratio Index (APRI) Values Over Time: Cohorts 1/1b
Week 24
|
0.310 numerical score
Standard Deviation 0.0970
|
0.513 numerical score
Standard Deviation 0.2892
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Day 2 (24-48 hr post-dose), Week 2, Week 4, Week 4 (24-48 hr post-dose), Week 6, Week 16, Week 16 (24-48 hr post-dose), Week 22, Week 28, Week 34, Week 40, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at given time point.
The APRI suggests the level of hepatic fibrosis and possible liver disease. APRI is calculated as 100\*(aspartate aminotransferase/40) / platelets. Scores indicate the following: \< 0.5 = fibrosis is ruled out; 0.5 - 0.7 = associated with some kind of liver damage; 0.7 - 1 = significant fibrosis; \> 1 = associated with cirrhosis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
APRI Values Over Time: Cohort 2
Baseline (Day 1)
|
0.500 numerical score
Standard Deviation 0.2102
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Day 2 (24-48 hr post-dose)
|
0.515 numerical score
Standard Deviation 0.2023
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 2
|
0.486 numerical score
Standard Deviation 0.1551
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 4
|
0.479 numerical score
Standard Deviation 0.2226
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 4 (24-48 hr post-dose)
|
0.454 numerical score
Standard Deviation 0.2127
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 6
|
0.463 numerical score
Standard Deviation 0.1678
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 16
|
0.372 numerical score
Standard Deviation 0.1812
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 16 (24-48 hr post-dose)
|
0.358 numerical score
Standard Deviation 0.2160
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 22
|
0.386 numerical score
Standard Deviation 0.2011
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 28
|
0.387 numerical score
Standard Deviation 0.2642
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 34
|
0.379 numerical score
Standard Deviation 0.2449
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 40
|
0.349 numerical score
Standard Deviation 0.1768
|
—
|
—
|
|
APRI Values Over Time: Cohort 2
Week 48
|
0.440 numerical score
Standard Deviation 0.2310
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 16, 24Population: Safety Analysis Set: all participants who received at least one dose of study drug.
PRO-C3 may be a biomarker for the formation of fibrotic tissue in the liver. For serum, the normal range is 6.1 - 13.8 ng/mL (based on a study of human serum samples from healthy men and women). Due to ethnic, dietary and age variations, the reference limits given may not apply to all populations. A reduction in Pro-C3 over time may indicate a reduction in hepatic fibrogenesis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
N-Terminal Type III Collagen Propeptide (PRO-C3) Values Over Time: Cohorts 1/1b
Baseline
|
16.78 μg/L
Standard Deviation 2.960
|
25.15 μg/L
Standard Deviation 9.310
|
—
|
|
N-Terminal Type III Collagen Propeptide (PRO-C3) Values Over Time: Cohorts 1/1b
Week 4
|
16.90 μg/L
Standard Deviation 3.539
|
22.10 μg/L
Standard Deviation 7.202
|
—
|
|
N-Terminal Type III Collagen Propeptide (PRO-C3) Values Over Time: Cohorts 1/1b
Week 16
|
15.60 μg/L
Standard Deviation 1.818
|
19.30 μg/L
Standard Deviation 0.245
|
—
|
|
N-Terminal Type III Collagen Propeptide (PRO-C3) Values Over Time: Cohorts 1/1b
Week 24
|
18.08 μg/L
Standard Deviation 2.159
|
16.63 μg/L
Standard Deviation 1.621
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 16, 28, 40, 48Population: Safety Analysis Set: all participants who received at least one dose of study drug.
PRO-C3 may be a biomarker for the formation of fibrotic tissue in the liver. For serum, the normal range is 6.1 - 13.8 ng/mL (based on a study of human serum samples from healthy men and women). Due to ethnic, dietary and age variations, the reference limits given may not apply to all populations. A reduction in Pro-C3 over time may indicate a reduction in hepatic fibrogenesis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
PRO-C3 Values Over Time: Cohort 2
Baseline
|
18.21 μg/L
Standard Deviation 3.002
|
—
|
—
|
|
PRO-C3 Values Over Time: Cohort 2
Week 4
|
15.81 μg/L
Standard Deviation 2.948
|
—
|
—
|
|
PRO-C3 Values Over Time: Cohort 2
Week 16
|
17.03 μg/L
Standard Deviation 2.463
|
—
|
—
|
|
PRO-C3 Values Over Time: Cohort 2
Week 28
|
14.31 μg/L
Standard Deviation 2.362
|
—
|
—
|
|
PRO-C3 Values Over Time: Cohort 2
Week 40
|
15.10 μg/L
Standard Deviation 2.989
|
—
|
—
|
|
PRO-C3 Values Over Time: Cohort 2
Week 48
|
17.09 μg/L
Standard Deviation 7.967
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug.
FibroScan is a type of liver elastography. Normal results are usually between 2 and 7 kilopascals (kPa), with results higher than the normal range if liver disease is present. The highest possible result is 75 kPa.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
FibroScan® Values Over Time: Cohorts 1/1b
Baseline
|
7.28 kPa
Standard Deviation 2.632
|
12.70 kPa
Standard Deviation 6.988
|
—
|
|
FibroScan® Values Over Time: Cohorts 1/1b
Week 24
|
7.30 kPa
Standard Deviation 3.730
|
10.55 kPa
Standard Deviation 5.802
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at given time point.
FibroScan is a type of liver elastography. Normal results are usually between 2 and 7 kilopascals (kPa), with results higher than the normal range if liver disease is present. The highest possible result is 75 kPa.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
FibroScan® Values Over Time: Cohort 2
Baseline
|
9.89 kPa
Standard Deviation 3.205
|
—
|
—
|
|
FibroScan® Values Over Time: Cohort 2
Week 48
|
8.67 kPa
Standard Deviation 3.263
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of portal inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Portal Inflammation Over Time: Cohorts 1/1b
≥ 1-point improvement
|
25.0 percentage of participants
|
50.0 percentage of participants
|
—
|
|
Portal Inflammation Over Time: Cohorts 1/1b
no change
|
50.0 percentage of participants
|
50.0 percentage of participants
|
—
|
|
Portal Inflammation Over Time: Cohorts 1/1b
≥ 1-point worsening
|
25.0 percentage of participants
|
0.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of portal inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Portal Inflammation Over Time: Cohort 2
≥ 1-point improvement
|
12.5 percentage of participants
|
—
|
—
|
|
Portal Inflammation Over Time: Cohort 2
no change
|
37.5 percentage of participants
|
—
|
—
|
|
Portal Inflammation Over Time: Cohort 2
≥ 1-point worsening
|
0.0 percentage of participants
|
—
|
—
|
|
Portal Inflammation Over Time: Cohort 2
Baseline score = 0
|
50.0 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of interface hepatitis, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Interface Hepatitis Over Time: Cohorts 1/1b
Baseline score = 0
|
25.0 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Interface Hepatitis Over Time: Cohorts 1/1b
≥ 1-point improvement
|
50.0 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Interface Hepatitis Over Time: Cohorts 1/1b
no change
|
0.0 percentage of participants
|
100.0 percentage of participants
|
—
|
|
Interface Hepatitis Over Time: Cohorts 1/1b
≥ 1-point worsening
|
25.0 percentage of participants
|
0.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of interface hepatitis, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Interface Hepatitis Over Time: Cohort 2
≥ 1-point improvement
|
25.0 percentage of participants
|
—
|
—
|
|
Interface Hepatitis Over Time: Cohort 2
no change
|
25.0 percentage of participants
|
—
|
—
|
|
Interface Hepatitis Over Time: Cohort 2
≥ 1-point worsening
|
0.0 percentage of participants
|
—
|
—
|
|
Interface Hepatitis Over Time: Cohort 2
Baseline score = 0
|
50.0 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of lobular inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Lobular Inflammation Over Time: Cohorts 1/1b
≥ 1-point improvement
|
0.0 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Lobular Inflammation Over Time: Cohorts 1/1b
no change
|
25.0 percentage of participants
|
50.0 percentage of participants
|
—
|
|
Lobular Inflammation Over Time: Cohorts 1/1b
≥ 1-point worsening
|
50.0 percentage of participants
|
50.0 percentage of participants
|
—
|
|
Lobular Inflammation Over Time: Cohorts 1/1b
Baseline score = 0
|
25.0 percentage of participants
|
0.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of lobular inflammation, which was scored on a scale from 0 (none) to 3 (severe). Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Lobular Inflammation Over Time: Cohort 2
≥ 1-point improvement
|
0.0 percentage of participants
|
—
|
—
|
|
Lobular Inflammation Over Time: Cohort 2
no change
|
62.5 percentage of participants
|
—
|
—
|
|
Lobular Inflammation Over Time: Cohort 2
≥ 1-point worsening
|
12.5 percentage of participants
|
—
|
—
|
|
Lobular Inflammation Over Time: Cohort 2
Baseline score = 0
|
25.0 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1- point worsening from the baseline category in the liver biopsy parameter of hepatocyte cell death. Hepatocyte Cell Death Score: 0 = No acidophil bodies; 1 = Few acidophil bodies; 2 = Many acidophil. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Hepatocyte Cell Death Over Time: Cohorts 1/1b
≥ 1-point improvement
|
0.0 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Hepatocyte Cell Death Over Time: Cohorts 1/1b
no change
|
25.0 percentage of participants
|
0.0 percentage of participants
|
—
|
|
Hepatocyte Cell Death Over Time: Cohorts 1/1b
≥ 1-point worsening
|
25.0 percentage of participants
|
25.0 percentage of participants
|
—
|
|
Hepatocyte Cell Death Over Time: Cohorts 1/1b
Baseline score = 0
|
50.0 percentage of participants
|
75.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1-point worsening from the baseline category in the liver biopsy parameter of hepatocyte cell death. Hepatocyte Cell Death Score: 0 = No acidophil bodies; 1 = Few acidophil bodies; 2 = Many acidophil. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Hepatocyte Cell Death Over Time: Cohort 2
≥ 1-point improvement
|
0.0 percentage of participants
|
—
|
—
|
|
Hepatocyte Cell Death Over Time: Cohort 2
no change
|
62.5 percentage of participants
|
—
|
—
|
|
Hepatocyte Cell Death Over Time: Cohort 2
≥ 1-point worsening
|
0.0 percentage of participants
|
—
|
—
|
|
Hepatocyte Cell Death Over Time: Cohort 2
Baseline score = 0
|
37.5 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety Analysis Set: all participants who received at least one dose of study drug. Participants with an assessment at the given time point.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1- point worsening from the baseline category in the METAVIR fibrosis stage score. The METAVIR scoring system is a system used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C. The stage represents the amount of fibrosis or scarring. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis. F0: no fibrosis F1: portal fibrosis without septa F2: portal fibrosis with few septa F3: numerous septa without cirrhosis F4: cirrhosis
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=3 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohorts 1/1b
≥ 1-point improvement
|
0.0 percentage of participants
|
50.0 percentage of participants
|
—
|
|
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohorts 1/1b
no change
|
100.0 percentage of participants
|
50.0 percentage of participants
|
—
|
|
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohorts 1/1b
≥ 1-point worsening
|
0.0 percentage of participants
|
0.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set: all participants who received at least one dose of study drug.
Percent of participants having ≥ 1-point improvement from baseline, no change from baseline, and ≥ 1- point worsening from the baseline category in the METAVIR fibrosis stage score. The METAVIR scoring system is a system used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C. The stage represents the amount of fibrosis or scarring. Participants with a baseline score of 0 were not included in any of the 3 categories for this analysis. F0: no fibrosis F1: portal fibrosis without septa F2: portal fibrosis with few septa F3: numerous septa without cirrhosis F4: cirrhosis
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=8 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohort 2
≥ 1-point improvement
|
50.0 percentage of participants
|
—
|
—
|
|
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohort 2
no change
|
12.5 percentage of participants
|
—
|
—
|
|
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohort 2
≥ 1-point worsening
|
25.0 percentage of participants
|
—
|
—
|
|
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Stage Score Over Time: Cohort 2
Baseline score = 0
|
12.5 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From first dose of study drug up to a maximum duration of study follow-up of 202 weeks.Population: Safety Analysis Set: all participants who received at least one dose of study drug.
An Adverse Event (AE) is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. Serious Adverse Event (SAE) is an AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is a medically important event or reaction. TEAEs are AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. Not related events include those reported as 'Not Related' to study drug. Related events include those reported as 'Possibly Related' or 'Probably Related' to study drug.
Outcome measures
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 Participants
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
n=8 Participants
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
≥ 1 TEAE
|
4 participants
|
4 participants
|
8 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
≥ 1 Serious TEAE
|
0 participants
|
3 participants
|
5 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Severity = Mild
|
3 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Severity = Moderate
|
1 participants
|
3 participants
|
4 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Severity = Severe
|
0 participants
|
0 participants
|
2 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE = Not Related to Study Drug (SD)
|
1 participants
|
2 participants
|
3 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE = Related to SD
|
3 participants
|
2 participants
|
5 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Injection Site Reaction (ISR) Severity = Mild
|
2 participants
|
1 participants
|
3 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE ISR Severity = Moderate
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE ISR Severity = Severe
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Leading to SD Discontinuation
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Requiring Dose Interruption of SD
|
0 participants
|
1 participants
|
3 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Leading to PRemature Withdrawal From Study
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE Causing Death
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
ARO-AAT 100 mg Cohort 1b
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
ARO-AAT 200 mg Cohort 1
Serious events: 4 serious events
Other events: 4 other events
Deaths: 0 deaths
ARO-AAT 200 mg Cohort 2
Serious events: 5 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 participants at risk
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 participants at risk
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
n=8 participants at risk
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Injury, poisoning and procedural complications
Procedural pneumothorax
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Syncope
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Vestibular neuronitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Viral myocarditis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
Other adverse events
| Measure |
ARO-AAT 100 mg Cohort 1b
n=4 participants at risk
Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous ARO-AAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W. As of global protocol version 7.0 (21-Jul-2022) / German protocol version 2.6 (29-Jul-2022) and after applicable regulatory, Ethics Committee and local approval, participants in Cohort 1b switched from 100 mg to 200 mg while maintaining their dosing schedule.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 1
n=4 participants at risk
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 15 doses.
|
ARO-AAT 200 mg Cohort 2
n=8 participants at risk
Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous ARO-AAT Q12W. Treatment Extension II (up to 24 months): 200 mg dose of subcutaneous ARO-AAT Q12W.
The maximum number of doses for participants completing the treatment extension periods was 17 doses.
|
|---|---|---|---|
|
Vascular disorders
Hypertension
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
2/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Vascular disorders
Hot flush
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Surgical and medical procedures
Dental implantation
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Chest pain
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
37.5%
3/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Injection site reaction
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
2/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Fatigue
|
50.0%
2/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Injection site bruising
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Injection site erythema
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Injection site inflammation
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Injection site pain
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
General disorders
Injection site pruritus
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Social circumstances
Denture wearer
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
2/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Psychiatric disorders
Loss of libido
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Blood creatine phosphokinase increased
|
50.0%
2/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
2/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Blood glucose increased
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Blood potassium increased
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
C-reactive protein increased
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Coagulation test abnormal
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
SARS-CoV-2 test positive
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Blood creatinine increased
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Heart rate irregular
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Investigations
Spirometry abnormal
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Injury, poisoning and procedural complications
Vaccination complication
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Cardiac disorders
Extrasystoles
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Dizziness
|
50.0%
2/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Headache
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
50.0%
2/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Lethargy
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Sciatica
|
50.0%
2/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Piriformis syndrome
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Nervous system disorders
Restless legs syndrome
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Ear and labyrinth disorders
Deafness
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Eye disorders
Dry eye
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Eye disorders
Visual impairment
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
37.5%
3/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
37.5%
3/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Oesophageal discomfort
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Aphthous ulcer
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Haemorrhoids
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Gastrointestinal disorders
Inguinal hernia
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
50.0%
2/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Renal and urinary disorders
Incontinence
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Renal and urinary disorders
Nephrolithiasis
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Renal and urinary disorders
Pollakiuria
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
37.5%
3/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
50.0%
2/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
2/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Nasopharyngitis
|
75.0%
3/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
100.0%
4/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
75.0%
6/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
COVID-19
|
75.0%
3/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
75.0%
3/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
50.0%
4/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Anal candidiasis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Candida infection
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Gastrointestinal infection
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Hepatitis E
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Sinusitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Coronavirus infection
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Influenza
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Otitis media
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Pulpitis dental
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Tooth infection
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Urinary tract infection
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Viral infection
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Infections and infestations
Colitis
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
12.5%
1/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
|
Metabolism and nutrition disorders
Gout
|
25.0%
1/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/4 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
0.00%
0/8 • For a maximum duration of study follow-up of 202 weeks.
Includes SAEs from time of screening.
|
Additional Information
Chief Operating Officer
Arrowhead Pharmaceuticals, Inc.
Phone: 1 (626) 304-3400
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor retains first right to publish results for this multi-center study, and thereafter can review results communications prior to release and can embargo communications regarding trial results for a period that is 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication of results but can require removal of its confidential information (excluding results).
- Publication restrictions are in place
Restriction type: OTHER