Trial Outcomes & Findings for A Study to Assess Subcutaneous Lirentelimab (AK002) in Chronic Spontaneous Urticaria (NCT NCT05528861)
NCT ID: NCT05528861
Last Updated: 2024-09-27
Results Overview
The UAS7 is the sum for 7 days of the daily Hives Severity Score (HSS) and the daily Itch Severity Score (ISS). The daily HSS is recorded on a scale of 0 (none) to 3 (\>50 hives) and the daily ISS is recorded on a scale of 0 (none) to 3 (severe). Therefore, the possible range of the weekly UAS7 score is 0-42, with 42 being the most severe.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
127 participants
Primary outcome timeframe
Baseline to Week 12
Results posted on
2024-09-27
Participant Flow
127 subjects who were enrolled in the main study received up to 6 doses of AK002 or placebo. 117 subjects from the main study continued into the open-label extension (OLE) period and received up to 6 doses of AK002.
Participant milestones
| Measure |
AK002 SC 300 mg (Main Study) - AK002 Continuing (OLE)
For the main study period, subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously (SC) every 2 weeks.
For the open-label extension (OLE) period, subjects who completed the main study and met eligibility criteria had the option to receive up to 6 doses of AK002 SC.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study) - Placebo Rollover (OLE)
For the main study period, subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks.
For the open-label extension (OLE) period, subjects who completed the main study and met eligibility criteria had the option to rollover and receive up to 6 doses of 300 mg AK002 SC.
Placebo: Placebo
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
|---|---|---|
|
Main Study
STARTED
|
66
|
61
|
|
Main Study
COMPLETED
|
60
|
57
|
|
Main Study
NOT COMPLETED
|
6
|
4
|
|
Open-Label Extension
STARTED
|
60
|
57
|
|
Open-Label Extension
COMPLETED
|
27
|
30
|
|
Open-Label Extension
NOT COMPLETED
|
33
|
27
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess Subcutaneous Lirentelimab (AK002) in Chronic Spontaneous Urticaria
Baseline characteristics by cohort
| Measure |
AK002 SC 300 mg (Main Study)
n=66 Participants
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=61 Participants
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
Total
n=127 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41 years
n=99 Participants
|
43 years
n=107 Participants
|
41 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=99 Participants
|
57 Participants
n=107 Participants
|
107 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=99 Participants
|
51 Participants
n=107 Participants
|
107 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
54 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
97 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
57 Participants
n=99 Participants
|
55 Participants
n=107 Participants
|
112 Participants
n=206 Participants
|
|
Region of Enrollment
Poland
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Region of Enrollment
Germany
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Weekly Urticaria Assessment Score (UAS7)
|
31.0 Score on a scale
STANDARD_DEVIATION 7.4 • n=99 Participants
|
31.9 Score on a scale
STANDARD_DEVIATION 7.8 • n=107 Participants
|
31.4 Score on a scale
STANDARD_DEVIATION 7.6 • n=206 Participants
|
|
Weekly Hive Severity Score (HSS7)
|
14.9 Score on a scale
STANDARD_DEVIATION 4.2 • n=99 Participants
|
15.8 Score on a scale
STANDARD_DEVIATION 4.0 • n=107 Participants
|
15.3 Score on a scale
STANDARD_DEVIATION 4.2 • n=206 Participants
|
|
Weekly Itch Severity Score (ISS7)
|
16.1 Score on a scale
STANDARD_DEVIATION 4.4 • n=99 Participants
|
16.1 Score on a scale
STANDARD_DEVIATION 4.3 • n=107 Participants
|
16.1 Score on a scale
STANDARD_DEVIATION 4.4 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: Modified Intent-to-Treat Population
The UAS7 is the sum for 7 days of the daily Hives Severity Score (HSS) and the daily Itch Severity Score (ISS). The daily HSS is recorded on a scale of 0 (none) to 3 (\>50 hives) and the daily ISS is recorded on a scale of 0 (none) to 3 (severe). Therefore, the possible range of the weekly UAS7 score is 0-42, with 42 being the most severe.
Outcome measures
| Measure |
AK002 SC 300 mg (Main Study)
n=64 Participants
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=59 Participants
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
|---|---|---|
|
Absolute Change in Weekly Urticaria Assessment Score (UAS7) From Baseline at Week 12
|
-7.9 score on a scale
Standard Error 1.9
|
-8.4 score on a scale
Standard Error 2.0
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: Modified Intent-to-Treat Population
The severity of hives will be recorded by all subjects once daily on a scale of 0 (none) to 3 (\> 50 hives). A weekly HSS score (HSS7) is derived by adding the average daily scores of the 7 days preceding the visit. Therefore, the possible range of the weekly score is 0 - 21.
Outcome measures
| Measure |
AK002 SC 300 mg (Main Study)
n=64 Participants
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=59 Participants
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
|---|---|---|
|
Absolute Change in Hives Severity Score (HSS7) From Baseline at Week 12
|
-4.0 score on a scale
Standard Error 0.8
|
-4.6 score on a scale
Standard Error 0.9
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: Modified Intent-to-Treat Population
The severity of itching will be recorded by all subjects once daily on a scale of 0 (none) to 3 (severe). A weekly ISS score (ISS7) is derived by adding the average daily scores of the 7 days preceding the visit. Therefore, the possible range of the weekly score is 0 - 21.
Outcome measures
| Measure |
AK002 SC 300 mg (Main Study)
n=64 Participants
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=59 Participants
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
|---|---|---|
|
Absolute Change in Itch Severity Score (ISS7) From Baseline at Week 12
|
-4.4 score on a scale
Standard Error 0.8
|
-4.3 score on a scale
Standard Error 0.9
|
SECONDARY outcome
Timeframe: At Week 12Population: Modified Intent-to-Treat Population
The UAS7 is the sum for 7 days of the daily Hives Severity Score (HSS) and the daily Itch Severity Score (ISS). The possible range of the UAS7 is 0-42.
Outcome measures
| Measure |
AK002 SC 300 mg (Main Study)
n=64 Participants
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=59 Participants
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
|---|---|---|
|
Proportion of Subjects Achieving Weekly Urticaria Assessment Score (UAS7)=0 at Week 12
|
6.3 percentage of participants
|
0 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Through study completion, up to 34 weeks (open-label extension period)Adverse events were assessed throughout the open-label extension period.
Outcome measures
| Measure |
AK002 SC 300 mg (Main Study)
n=60 Participants
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=57 Participants
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
|---|---|---|
|
Safety and Tolerability of up to 6 Doses of Open-label AK002 in Subjects With Chronic Spontaneous Urticaria in the Open-label Extension Period
Subjects with ≥1 adverse events
|
31 Participants
|
26 Participants
|
|
Safety and Tolerability of up to 6 Doses of Open-label AK002 in Subjects With Chronic Spontaneous Urticaria in the Open-label Extension Period
Subjects with ≥1 treatment-related adverse events
|
6 Participants
|
12 Participants
|
|
Safety and Tolerability of up to 6 Doses of Open-label AK002 in Subjects With Chronic Spontaneous Urticaria in the Open-label Extension Period
Subjects with an adverse event leading to study drug discontinuation
|
4 Participants
|
1 Participants
|
|
Safety and Tolerability of up to 6 Doses of Open-label AK002 in Subjects With Chronic Spontaneous Urticaria in the Open-label Extension Period
Subjects with ≥1 serious adverse events
|
2 Participants
|
2 Participants
|
|
Safety and Tolerability of up to 6 Doses of Open-label AK002 in Subjects With Chronic Spontaneous Urticaria in the Open-label Extension Period
Subjects with ≥1 treatment-related serious adverse events
|
0 Participants
|
0 Participants
|
Adverse Events
AK002 SC 300 mg (Main Study)
Serious events: 1 serious events
Other events: 26 other events
Deaths: 0 deaths
Placebo (Main Study)
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
AK002 Continuing (OLE)
Serious events: 2 serious events
Other events: 22 other events
Deaths: 0 deaths
Placebo Rollover (OLE)
Serious events: 2 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AK002 SC 300 mg (Main Study)
n=66 participants at risk
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=61 participants at risk
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
AK002 Continuing (OLE)
n=60 participants at risk
Subjects in this arm received AK002 in the main study and continued to receive up to 6 doses of 300 mg AK002 SC in the open-label extension (OLE) period.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo Rollover (OLE)
n=57 participants at risk
Subjects in this arm received placebo in the main study and rolled over to receive up to 6 doses of 300 mg AK002 SC in the open-label extension (OLE) period.
Placebo: Placebo
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
|---|---|---|---|---|
|
Infections and infestations
COVID-19
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
1.6%
1/61 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/60 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Infections and infestations
Epiglottitis obstructive
|
1.5%
1/66 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/61 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/60 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/61 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/60 • Through study completion, up to 34 weeks (open-label extension period)
|
1.8%
1/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Injury, poisoning and procedural complications
Gun shot wound
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/61 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/60 • Through study completion, up to 34 weeks (open-label extension period)
|
1.8%
1/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/61 • Through study completion, up to 34 weeks (open-label extension period)
|
1.7%
1/60 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/61 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/60 • Through study completion, up to 34 weeks (open-label extension period)
|
1.8%
1/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Psychiatric disorders
Bipolar disorder
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/61 • Through study completion, up to 34 weeks (open-label extension period)
|
1.7%
1/60 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/61 • Through study completion, up to 34 weeks (open-label extension period)
|
1.7%
1/60 • Through study completion, up to 34 weeks (open-label extension period)
|
0.00%
0/57 • Through study completion, up to 34 weeks (open-label extension period)
|
Other adverse events
| Measure |
AK002 SC 300 mg (Main Study)
n=66 participants at risk
Subjects in this arm received up to 6 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks in the main study.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo (Main Study)
n=61 participants at risk
Subjects in this arm received up to 6 doses of placebo administered subcutaneously every 2 weeks in the main study.
Placebo: Placebo
|
AK002 Continuing (OLE)
n=60 participants at risk
Subjects in this arm received AK002 in the main study and continued to receive up to 6 doses of 300 mg AK002 SC in the open-label extension (OLE) period.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
Placebo Rollover (OLE)
n=57 participants at risk
Subjects in this arm received placebo in the main study and rolled over to receive up to 6 doses of 300 mg AK002 SC in the open-label extension (OLE) period.
Placebo: Placebo
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8
|
|---|---|---|---|---|
|
General disorders
Injection site reaction
|
21.2%
14/66 • Through study completion, up to 34 weeks (open-label extension period)
|
9.8%
6/61 • Through study completion, up to 34 weeks (open-label extension period)
|
6.7%
4/60 • Through study completion, up to 34 weeks (open-label extension period)
|
15.8%
9/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Infections and infestations
Nasopharyngitis
|
9.1%
6/66 • Through study completion, up to 34 weeks (open-label extension period)
|
4.9%
3/61 • Through study completion, up to 34 weeks (open-label extension period)
|
8.3%
5/60 • Through study completion, up to 34 weeks (open-label extension period)
|
1.8%
1/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Infections and infestations
Upper respiratory tract infection
|
3.0%
2/66 • Through study completion, up to 34 weeks (open-label extension period)
|
8.2%
5/61 • Through study completion, up to 34 weeks (open-label extension period)
|
5.0%
3/60 • Through study completion, up to 34 weeks (open-label extension period)
|
1.8%
1/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Injury, poisoning and procedural complications
Injection related reaction
|
18.2%
12/66 • Through study completion, up to 34 weeks (open-label extension period)
|
8.2%
5/61 • Through study completion, up to 34 weeks (open-label extension period)
|
1.7%
1/60 • Through study completion, up to 34 weeks (open-label extension period)
|
8.8%
5/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Skin and subcutaneous tissue disorders
Chronic spontaneous urticaria
|
3.0%
2/66 • Through study completion, up to 34 weeks (open-label extension period)
|
4.9%
3/61 • Through study completion, up to 34 weeks (open-label extension period)
|
10.0%
6/60 • Through study completion, up to 34 weeks (open-label extension period)
|
3.5%
2/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Infections and infestations
Urinary tract infection
|
3.0%
2/66 • Through study completion, up to 34 weeks (open-label extension period)
|
4.9%
3/61 • Through study completion, up to 34 weeks (open-label extension period)
|
8.3%
5/60 • Through study completion, up to 34 weeks (open-label extension period)
|
1.8%
1/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Infections and infestations
COVID-19
|
0.00%
0/66 • Through study completion, up to 34 weeks (open-label extension period)
|
1.6%
1/61 • Through study completion, up to 34 weeks (open-label extension period)
|
5.0%
3/60 • Through study completion, up to 34 weeks (open-label extension period)
|
3.5%
2/57 • Through study completion, up to 34 weeks (open-label extension period)
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
3.0%
2/66 • Through study completion, up to 34 weeks (open-label extension period)
|
3.3%
2/61 • Through study completion, up to 34 weeks (open-label extension period)
|
5.0%
3/60 • Through study completion, up to 34 weeks (open-label extension period)
|
8.8%
5/57 • Through study completion, up to 34 weeks (open-label extension period)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Clinical Trial Agreement contains a limit on publication of results following completion of the trial. PIs are not allowed to publish results until a joint publication for the multicenter study or a set period of time. After that time, PIs may only publish results from their portion of the study.
- Publication restrictions are in place
Restriction type: OTHER