Trial Outcomes & Findings for Study of ISIS 703802 in Participants With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease (NCT NCT03371355)
NCT ID: NCT03371355
Last Updated: 2021-02-01
Results Overview
An ANCOVA model was performed on the log ratio of Primary Analysis Time Point to Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Primary Analysis Time Point to Baseline - 1) × 100.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
105 participants
Primary outcome timeframe
Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C
Results posted on
2021-02-01
Participant Flow
The study was conducted at 42 study centers; 38 sites in the US and 4 sites in Canada.
A total of 525 participants were screened. 105 were randomized in a 1:1:1 ratio to Cohorts A, B, or C. In each cohort, participants were randomized in a 3:1 ratio to receive ISIS 703802 or matching volume of placebo.
Participant milestones
| Measure |
Pooled Placebo
Participants from each cohort received placebo at a dose-matched volume of study drug, subcutaneously (SC).
|
Cohort B: ISIS 703802, 40 mg Q4W
Participants received ISIS 703802, 40 milligrams (mg) SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
27
|
26
|
26
|
26
|
|
Overall Study
COMPLETED
|
26
|
24
|
22
|
19
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
4
|
7
|
Reasons for withdrawal
| Measure |
Pooled Placebo
Participants from each cohort received placebo at a dose-matched volume of study drug, subcutaneously (SC).
|
Cohort B: ISIS 703802, 40 mg Q4W
Participants received ISIS 703802, 40 milligrams (mg) SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Overall Study
Investigator judgment
|
0
|
0
|
1
|
1
|
|
Overall Study
Voluntary withdrawal
|
1
|
0
|
1
|
2
|
|
Overall Study
Adverse Event
|
0
|
1
|
2
|
3
|
|
Overall Study
Reason not Specified
|
0
|
1
|
0
|
1
|
Baseline Characteristics
Number analyzed signifies the number of participants with data available for LDL-C.
Baseline characteristics by cohort
| Measure |
Pooled Placebo
n=27 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=26 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=26 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=26 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
Total
n=105 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
51.1 years
STANDARD_DEVIATION 7.29 • n=27 Participants
|
52.0 years
STANDARD_DEVIATION 10.34 • n=26 Participants
|
54.8 years
STANDARD_DEVIATION 6.04 • n=26 Participants
|
56.0 years
STANDARD_DEVIATION 8.45 • n=26 Participants
|
53.5 years
STANDARD_DEVIATION 8.30 • n=105 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=27 Participants
|
9 Participants
n=26 Participants
|
13 Participants
n=26 Participants
|
11 Participants
n=26 Participants
|
49 Participants
n=105 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=27 Participants
|
17 Participants
n=26 Participants
|
13 Participants
n=26 Participants
|
15 Participants
n=26 Participants
|
56 Participants
n=105 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
24 Participants
n=27 Participants
|
13 Participants
n=26 Participants
|
11 Participants
n=26 Participants
|
17 Participants
n=26 Participants
|
65 Participants
n=105 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=27 Participants
|
13 Participants
n=26 Participants
|
15 Participants
n=26 Participants
|
9 Participants
n=26 Participants
|
40 Participants
n=105 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=27 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=27 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=27 Participants
|
1 Participants
n=26 Participants
|
1 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
3 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=27 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=27 Participants
|
2 Participants
n=26 Participants
|
1 Participants
n=26 Participants
|
1 Participants
n=26 Participants
|
5 Participants
n=105 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=27 Participants
|
23 Participants
n=26 Participants
|
24 Participants
n=26 Participants
|
25 Participants
n=26 Participants
|
97 Participants
n=105 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=27 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=27 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=105 Participants
|
|
Fasting Triglycerides (TG)
|
275.5 milligrams per deciliter (mg/dL)
STANDARD_DEVIATION 110.38 • n=27 Participants
|
414.9 milligrams per deciliter (mg/dL)
STANDARD_DEVIATION 456.86 • n=26 Participants
|
292.2 milligrams per deciliter (mg/dL)
STANDARD_DEVIATION 130.98 • n=26 Participants
|
311.8 milligrams per deciliter (mg/dL)
STANDARD_DEVIATION 155.92 • n=26 Participants
|
323.1 milligrams per deciliter (mg/dL)
STANDARD_DEVIATION 257.20 • n=105 Participants
|
|
Angiopoietin Like 3 (ANGPTL3)
|
114.85 micrograms per liter (μg/L)
STANDARD_DEVIATION 32.066 • n=27 Participants
|
102.36 micrograms per liter (μg/L)
STANDARD_DEVIATION 28.923 • n=26 Participants
|
111.86 micrograms per liter (μg/L)
STANDARD_DEVIATION 37.463 • n=26 Participants
|
108.60 micrograms per liter (μg/L)
STANDARD_DEVIATION 42.722 • n=26 Participants
|
109.47 micrograms per liter (μg/L)
STANDARD_DEVIATION 35.441 • n=105 Participants
|
|
Total Cholesterol (TC)
|
202.1 mg/dL
STANDARD_DEVIATION 43.64 • n=27 Participants
|
200.7 mg/dL
STANDARD_DEVIATION 45.27 • n=26 Participants
|
191.2 mg/dL
STANDARD_DEVIATION 61.63 • n=26 Participants
|
182.4 mg/dL
STANDARD_DEVIATION 47.06 • n=26 Participants
|
194.2 mg/dL
STANDARD_DEVIATION 49.78 • n=105 Participants
|
|
Non- High density lipoprotein cholesterol (Non-HDL-C)
|
162.7 mg/dL
STANDARD_DEVIATION 39.90 • n=27 Participants
|
164.3 mg/dL
STANDARD_DEVIATION 47.50 • n=26 Participants
|
154.1 mg/dL
STANDARD_DEVIATION 58.28 • n=26 Participants
|
146.8 mg/dL
STANDARD_DEVIATION 46.79 • n=26 Participants
|
157.0 mg/dL
STANDARD_DEVIATION 48.30 • n=105 Participants
|
|
High density lipoprotein cholesterol (HDL-C)
|
39.4 mg/dL
STANDARD_DEVIATION 10.43 • n=27 Participants
|
36.3 mg/dL
STANDARD_DEVIATION 10.54 • n=26 Participants
|
37.1 mg/dL
STANDARD_DEVIATION 10.37 • n=26 Participants
|
35.6 mg/dL
STANDARD_DEVIATION 9.89 • n=26 Participants
|
37.1 mg/dL
STANDARD_DEVIATION 10.26 • n=105 Participants
|
|
Low Density Lipoprotein Cholesterol (LDL-C)
|
111.5 mg/dL
STANDARD_DEVIATION 43.06 • n=25 Participants • Number analyzed signifies the number of participants with data available for LDL-C.
|
98.2 mg/dL
STANDARD_DEVIATION 36.13 • n=23 Participants • Number analyzed signifies the number of participants with data available for LDL-C.
|
101.0 mg/dL
STANDARD_DEVIATION 53.13 • n=23 Participants • Number analyzed signifies the number of participants with data available for LDL-C.
|
88.6 mg/dL
STANDARD_DEVIATION 37.69 • n=25 Participants • Number analyzed signifies the number of participants with data available for LDL-C.
|
99.8 mg/dL
STANDARD_DEVIATION 43.05 • n=96 Participants • Number analyzed signifies the number of participants with data available for LDL-C.
|
|
Very Low Density Lipoprotein Cholesterol (VLDL-C)
|
47.8 mg/dL
STANDARD_DEVIATION 12.90 • n=25 Participants • Number analyzed signifies the number of participants with data available for VLDL-C.
|
52.6 mg/dL
STANDARD_DEVIATION 14.59 • n=23 Participants • Number analyzed signifies the number of participants with data available for VLDL-C.
|
47.6 mg/dL
STANDARD_DEVIATION 9.92 • n=23 Participants • Number analyzed signifies the number of participants with data available for VLDL-C.
|
49.6 mg/dL
STANDARD_DEVIATION 13.11 • n=25 Participants • Number analyzed signifies the number of participants with data available for VLDL-C.
|
49.4 mg/dL
STANDARD_DEVIATION 12.71 • n=96 Participants • Number analyzed signifies the number of participants with data available for VLDL-C.
|
|
Apolipoprotein CIII (ApoCIII)
|
14.48 mg/dL
STANDARD_DEVIATION 3.981 • n=27 Participants
|
18.71 mg/dL
STANDARD_DEVIATION 11.024 • n=26 Participants
|
15.54 mg/dL
STANDARD_DEVIATION 4.969 • n=26 Participants
|
16.19 mg/dL
STANDARD_DEVIATION 5.562 • n=26 Participants
|
16.21 mg/dL
STANDARD_DEVIATION 7.000 • n=105 Participants
|
|
Apolipoprotein A1 (ApoA1)
|
141.3 mg/dL
STANDARD_DEVIATION 19.30 • n=27 Participants
|
137.9 mg/dL
STANDARD_DEVIATION 21.12 • n=26 Participants
|
139.1 mg/dL
STANDARD_DEVIATION 24.12 • n=26 Participants
|
133.3 mg/dL
STANDARD_DEVIATION 20.18 • n=26 Participants
|
137.9 mg/dL
STANDARD_DEVIATION 21.13 • n=105 Participants
|
|
Apolipoprotein B (ApoB)
|
108.68 mg/dL
STANDARD_DEVIATION 25.254 • n=27 Participants
|
105.90 mg/dL
STANDARD_DEVIATION 25.868 • n=26 Participants
|
105.34 mg/dL
STANDARD_DEVIATION 36.160 • n=26 Participants
|
95.48 mg/dL
STANDARD_DEVIATION 26.210 • n=26 Participants
|
103.90 mg/dL
STANDARD_DEVIATION 28.721 • n=105 Participants
|
|
Apolipoprotein B48 (ApoB-48)
|
2.63 mg/dL
STANDARD_DEVIATION 1.455 • n=27 Participants
|
3.21 mg/dL
STANDARD_DEVIATION 2.239 • n=26 Participants
|
3.20 mg/dL
STANDARD_DEVIATION 2.863 • n=26 Participants
|
3.48 mg/dL
STANDARD_DEVIATION 3.228 • n=26 Participants
|
3.13 mg/dL
STANDARD_DEVIATION 2.511 • n=105 Participants
|
|
Apolipoprotein B100 (ApoB-100)
|
105.89 mg/dL
STANDARD_DEVIATION 25.699 • n=27 Participants
|
102.48 mg/dL
STANDARD_DEVIATION 25.740 • n=26 Participants
|
102.14 mg/dL
STANDARD_DEVIATION 35.392 • n=26 Participants
|
91.79 mg/dL
STANDARD_DEVIATION 25.871 • n=26 Participants
|
100.62 mg/dL
STANDARD_DEVIATION 28.540 • n=105 Participants
|
|
Lipoprotein-a (Lp[a])
|
51.7 nanomoles per liter (nmol/L)
STANDARD_DEVIATION 66.79 • n=27 Participants
|
58.2 nanomoles per liter (nmol/L)
STANDARD_DEVIATION 74.74 • n=26 Participants
|
46.7 nanomoles per liter (nmol/L)
STANDARD_DEVIATION 74.88 • n=26 Participants
|
38.3 nanomoles per liter (nmol/L)
STANDARD_DEVIATION 54.81 • n=26 Participants
|
48.8 nanomoles per liter (nmol/L)
STANDARD_DEVIATION 67.69 • n=105 Participants
|
|
Free Fatty Acid (FFA)
|
0.62 millimole per liter (mmol/L)
STANDARD_DEVIATION 0.261 • n=27 Participants
|
0.66 millimole per liter (mmol/L)
STANDARD_DEVIATION 0.266 • n=26 Participants
|
0.61 millimole per liter (mmol/L)
STANDARD_DEVIATION 0.237 • n=26 Participants
|
0.58 millimole per liter (mmol/L)
STANDARD_DEVIATION 0.213 • n=26 Participants
|
0.62 millimole per liter (mmol/L)
STANDARD_DEVIATION 0.243 • n=105 Participants
|
|
Insulin
|
26.35 milli international units per liter
STANDARD_DEVIATION 16.965 • n=27 Participants • Number analyzed signifies the number of participants with data available for insulin.
|
21.35 milli international units per liter
STANDARD_DEVIATION 12.602 • n=26 Participants • Number analyzed signifies the number of participants with data available for insulin.
|
26.32 milli international units per liter
STANDARD_DEVIATION 15.353 • n=25 Participants • Number analyzed signifies the number of participants with data available for insulin.
|
23.19 milli international units per liter
STANDARD_DEVIATION 12.887 • n=25 Participants • Number analyzed signifies the number of participants with data available for insulin.
|
24.31 milli international units per liter
STANDARD_DEVIATION 14.542 • n=103 Participants • Number analyzed signifies the number of participants with data available for insulin.
|
|
Plasma Glucose
|
188.6 mg/dL
STANDARD_DEVIATION 59.06 • n=27 Participants • Number analyzed signifies the number of participants with data available for plasma glucose.
|
182.6 mg/dL
STANDARD_DEVIATION 58.87 • n=26 Participants • Number analyzed signifies the number of participants with data available for plasma glucose.
|
201.4 mg/dL
STANDARD_DEVIATION 52.16 • n=25 Participants • Number analyzed signifies the number of participants with data available for plasma glucose.
|
164.6 mg/dL
STANDARD_DEVIATION 47.69 • n=25 Participants • Number analyzed signifies the number of participants with data available for plasma glucose.
|
184.4 mg/dL
STANDARD_DEVIATION 55.55 • n=103 Participants • Number analyzed signifies the number of participants with data available for plasma glucose.
|
|
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
|
12.40 index
STANDARD_DEVIATION 8.548 • n=27 Participants • Number analyzed signifies the number of participants with data available for HOMA-IR.
|
9.42 index
STANDARD_DEVIATION 6.178 • n=26 Participants • Number analyzed signifies the number of participants with data available for HOMA-IR.
|
13.02 index
STANDARD_DEVIATION 8.331 • n=25 Participants • Number analyzed signifies the number of participants with data available for HOMA-IR.
|
9.54 index
STANDARD_DEVIATION 6.278 • n=25 Participants • Number analyzed signifies the number of participants with data available for HOMA-IR.
|
11.10 index
STANDARD_DEVIATION 7.500 • n=103 Participants • Number analyzed signifies the number of participants with data available for HOMA-IR.
|
|
Fructosamine
|
325.2 micromoles per liter (μmol/L)
STANDARD_DEVIATION 49.62 • n=27 Participants
|
302.7 micromoles per liter (μmol/L)
STANDARD_DEVIATION 65.51 • n=26 Participants
|
317.6 micromoles per liter (μmol/L)
STANDARD_DEVIATION 59.33 • n=26 Participants
|
312.9 micromoles per liter (μmol/L)
STANDARD_DEVIATION 48.19 • n=26 Participants
|
314.7 micromoles per liter (μmol/L)
STANDARD_DEVIATION 55.85 • n=105 Participants
|
|
Glycated Albumin
|
0.84 grams per deciliter (g/dL)
STANDARD_DEVIATION 0.183 • n=27 Participants
|
0.74 grams per deciliter (g/dL)
STANDARD_DEVIATION 0.254 • n=26 Participants
|
0.80 grams per deciliter (g/dL)
STANDARD_DEVIATION 0.216 • n=26 Participants
|
0.79 grams per deciliter (g/dL)
STANDARD_DEVIATION 0.187 • n=26 Participants
|
0.79 grams per deciliter (g/dL)
STANDARD_DEVIATION 0.211 • n=105 Participants
|
|
Hemoglobin A1C (HbA1C)
|
8.30 percentage of HbA1c
STANDARD_DEVIATION 1.260 • n=27 Participants
|
8.04 percentage of HbA1c
STANDARD_DEVIATION 1.113 • n=26 Participants
|
8.36 percentage of HbA1c
STANDARD_DEVIATION 1.091 • n=26 Participants
|
8.19 percentage of HbA1c
STANDARD_DEVIATION 0.901 • n=26 Participants
|
8.22 percentage of HbA1c
STANDARD_DEVIATION 1.091 • n=105 Participants
|
|
Hepatic Fat Fraction (HFF)
|
16.84 percentage (Hepatic Fat Fraction)
STANDARD_DEVIATION 6.144 • n=27 Participants
|
17.17 percentage (Hepatic Fat Fraction)
STANDARD_DEVIATION 6.150 • n=26 Participants
|
17.23 percentage (Hepatic Fat Fraction)
STANDARD_DEVIATION 7.262 • n=26 Participants
|
19.32 percentage (Hepatic Fat Fraction)
STANDARD_DEVIATION 10.445 • n=26 Participants
|
17.63 percentage (Hepatic Fat Fraction)
STANDARD_DEVIATION 7.642 • n=105 Participants
|
|
Subcutaneous Adipose Tissue (SAT)
|
2634.49 millimeters square (mm^2)
STANDARD_DEVIATION 1235.433 • n=27 Participants
|
3076.36 millimeters square (mm^2)
STANDARD_DEVIATION 1114.681 • n=26 Participants
|
3021.37 millimeters square (mm^2)
STANDARD_DEVIATION 1080.432 • n=26 Participants
|
2701.94 millimeters square (mm^2)
STANDARD_DEVIATION 1000.756 • n=26 Participants
|
2856.41 millimeters square (mm^2)
STANDARD_DEVIATION 1113.220 • n=105 Participants
|
|
Visceral Adipose Tissue (VAT),
|
2275.05 mm^2
STANDARD_DEVIATION 605.492 • n=27 Participants
|
2690.34 mm^2
STANDARD_DEVIATION 888.431 • n=26 Participants
|
2826.84 mm^2
STANDARD_DEVIATION 1105.086 • n=26 Participants
|
2773.11 mm^2
STANDARD_DEVIATION 894.630 • n=26 Participants
|
2637.85 mm^2
STANDARD_DEVIATION 903.168 • n=105 Participants
|
|
Fatty Liver Index (FLI)
|
77.20 index
STANDARD_DEVIATION 22.618 • n=27 Participants • Number analyzed signifies the number of participants with data available for FLI.
|
85.55 index
STANDARD_DEVIATION 12.802 • n=25 Participants • Number analyzed signifies the number of participants with data available for FLI.
|
83.16 index
STANDARD_DEVIATION 19.846 • n=26 Participants • Number analyzed signifies the number of participants with data available for FLI.
|
84.45 index
STANDARD_DEVIATION 13.926 • n=26 Participants • Number analyzed signifies the number of participants with data available for FLI.
|
82.51 index
STANDARD_DEVIATION 17.907 • n=104 Participants • Number analyzed signifies the number of participants with data available for FLI.
|
|
Body Weight
|
79.3 kg
STANDARD_DEVIATION 10.64 • n=27 Participants
|
92.5 kg
STANDARD_DEVIATION 16.66 • n=26 Participants
|
90.7 kg
STANDARD_DEVIATION 20.83 • n=26 Participants
|
92.0 kg
STANDARD_DEVIATION 16.39 • n=26 Participants
|
88.5 kg
STANDARD_DEVIATION 17.15 • n=105 Participants
|
|
Body Mass Index (BMI)
|
30.3 kilograms per meter square (kg/m^2)
STANDARD_DEVIATION 3.03 • n=27 Participants
|
32.8 kilograms per meter square (kg/m^2)
STANDARD_DEVIATION 3.97 • n=26 Participants
|
32.1 kilograms per meter square (kg/m^2)
STANDARD_DEVIATION 3.84 • n=26 Participants
|
32.3 kilograms per meter square (kg/m^2)
STANDARD_DEVIATION 4.19 • n=26 Participants
|
31.9 kilograms per meter square (kg/m^2)
STANDARD_DEVIATION 3.84 • n=105 Participants
|
|
Waist to Hip Ratio
|
0.98 ratio
STANDARD_DEVIATION 0.070 • n=27 Participants • Number analyzed signifies the number of participants with data available for waist to hip ratio.
|
1.05 ratio
STANDARD_DEVIATION 0.225 • n=26 Participants • Number analyzed signifies the number of participants with data available for waist to hip ratio.
|
1.01 ratio
STANDARD_DEVIATION 0.216 • n=25 Participants • Number analyzed signifies the number of participants with data available for waist to hip ratio.
|
0.97 ratio
STANDARD_DEVIATION 0.068 • n=26 Participants • Number analyzed signifies the number of participants with data available for waist to hip ratio.
|
1.00 ratio
STANDARD_DEVIATION 0.163 • n=104 Participants • Number analyzed signifies the number of participants with data available for waist to hip ratio.
|
PRIMARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug.
An ANCOVA model was performed on the log ratio of Primary Analysis Time Point to Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Primary Analysis Time Point to Baseline - 1) × 100.
Outcome measures
| Measure |
Pooled Placebo
n=27 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=26 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=26 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=26 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Fasting Triglycerides Level at the Primary Analysis Time Point
|
-16 percent change
Interval -29.0 to 0.0
|
-36 percent change
Interval -47.0 to -23.0
|
-53 percent change
Interval -60.0 to -43.0
|
-47 percent change
Interval -57.0 to -35.0
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=17 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Angiopoietin-Like 3 Protein at the Primary Analysis Time Point
|
6.77 μg/L
Interval -2.09 to 15.62
|
-43.11 μg/L
Interval -52.27 to -33.94
|
-64.89 μg/L
Interval -74.26 to -55.53
|
-52.98 μg/L
Interval -63.99 to -41.96
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, 'number analyzed' (n) signifies participants evaluable for this outcome measure for each specified category.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=27 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=26 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=26 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=26 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
TC
|
-4.8 mg/dL
Interval -15.19 to 5.51
|
-21.3 mg/dL
Interval -32.35 to -10.31
|
-41.9 mg/dL
Interval -52.88 to -30.89
|
-36.5 mg/dL
Interval -49.38 to -23.58
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
LDL-C
|
-2.5 mg/dL
Interval -11.21 to 6.14
|
5.0 mg/dL
Interval -4.78 to 14.7
|
-11.1 mg/dL
Interval -20.38 to -1.9
|
-11.3 mg/dL
Interval -21.76 to -0.84
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
HDL-C
|
2.2 mg/dL
Interval -0.38 to 4.69
|
-0.6 mg/dL
Interval -3.25 to 2.14
|
-6.4 mg/dL
Interval -9.13 to -3.77
|
-2.0 mg/dL
Interval -5.11 to 1.12
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
VLDL-C
|
-6.5 mg/dL
Interval -11.64 to -1.34
|
-15.6 mg/dL
Interval -21.47 to -9.78
|
-21.9 mg/dL
Interval -27.41 to -16.36
|
-17.3 mg/dL
Interval -23.48 to -11.13
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
Non-HDL-C
|
-7.0 mg/dL
Interval -17.45 to 3.44
|
-20.9 mg/dL
Interval -32.01 to -9.7
|
-35.4 mg/dL
Interval -46.54 to -24.33
|
-34.4 mg/dL
Interval -47.39 to -21.34
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
ApoB
|
-3.63 mg/dL
Interval -9.98 to 2.71
|
-6.08 mg/dL
Interval -12.82 to 0.66
|
-13.46 mg/dL
Interval -20.2 to -6.72
|
-8.91 mg/dL
Interval -16.91 to -0.91
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
ApoB: ApoB-48
|
-0.139 mg/dL
Interval -0.9 to 0.62
|
-1.140 mg/dL
Interval -1.93 to -0.35
|
-1.942 mg/dL
Interval -2.75 to -1.14
|
-1.230 mg/dL
Interval -2.16 to -0.3
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
ApoB: ApoB-100
|
-3.757 mg/dL
Interval -9.94 to 2.43
|
-4.643 mg/dL
Interval -11.21 to 1.92
|
-11.346 mg/dL
Interval -17.91 to -4.78
|
-7.174 mg/dL
Interval -14.97 to 0.62
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
ApoCIII
|
-0.729 mg/dL
Interval -2.58 to 1.12
|
-5.482 mg/dL
Interval -7.42 to -3.54
|
-9.228 mg/dL
Interval -11.18 to -7.28
|
-7.588 mg/dL
Interval -9.86 to -5.32
|
|
Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point
ApoA1
|
5.0 mg/dL
Interval -1.11 to 11.15
|
-11.8 mg/dL
Interval -18.32 to -5.3
|
-30.1 mg/dL
Interval -36.63 to -23.65
|
-16.1 mg/dL
Interval -23.68 to -8.57
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=17 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Free Fatty Acid (FFA) at Primary Analysis Time Point
|
-0.0734 mmol/L
Interval -0.15 to 0.01
|
-0.0607 mmol/L
Interval -0.15 to 0.02
|
-0.0878 mmol/L
Interval -0.17 to 0.0
|
-0.0881 mmol/L
Interval -0.19 to 0.01
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=17 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Lipoprotein(a) (Lp[a]) at the Primary Analysis Time Point
|
-1.1 nmol/L
Interval -6.67 to 4.51
|
6.8 nmol/L
Interval 0.76 to 12.75
|
0.5 nmol/L
Interval -5.47 to 6.44
|
-2.8 nmol/L
Interval -9.74 to 4.15
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, 'n' signifies participants evaluable for this outcome measure for each specified category.
An ANCOVA model was performed on the log ratio of Primary Analysis Time Point to Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Primary Analysis Time Point to Baseline - 1) × 100.
Outcome measures
| Measure |
Pooled Placebo
n=27 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=26 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=26 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=26 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
ANGPTL3
|
8 percent change
Interval -6.0 to 23.0
|
-41 percent change
Interval -48.0 to -32.0
|
-59 percent change
Interval -64.0 to -53.0
|
-54 percent change
Interval -61.0 to -46.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
TC
|
-2 percent change
Interval -8.0 to 4.0
|
-11 percent change
Interval -16.0 to -5.0
|
-21 percent change
Interval -26.0 to -16.0
|
-19 percent change
Interval -25.0 to -13.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
LDL-C
|
0 percent change
Interval -8.0 to 9.0
|
6 percent change
Interval -4.0 to 17.0
|
-7 percent change
Interval -15.0 to 2.0
|
-12 percent change
Interval -21.0 to -3.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
HDL-C
|
7 percent change
Interval -2.0 to 16.0
|
-2 percent change
Interval -10.0 to 8.0
|
-18 percent change
Interval -25.0 to -11.0
|
-4 percent change
Interval -13.0 to 6.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
VLDL-C
|
-14 percent change
Interval -26.0 to 0.0
|
-35 percent change
Interval -45.0 to -23.0
|
-47 percent change
Interval -55.0 to -37.0
|
-40 percent change
Interval -50.0 to -28.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
Non-HDL-C
|
-4 percent change
Interval -11.0 to 3.0
|
-13 percent change
Interval -20.0 to -7.0
|
-21 percent change
Interval -27.0 to -15.0
|
-22 percent change
Interval -29.0 to -15.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
ApoB
|
-3 percent change
Interval -9.0 to 3.0
|
-7 percent change
Interval -12.0 to 0.0
|
-12 percent change
Interval -17.0 to -6.0
|
-10 percent change
Interval -17.0 to -3.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
ApoB: ApoB-48
|
-21 percent change
Interval -40.0 to 5.0
|
-44 percent change
Interval -58.0 to -25.0
|
-62 percent change
Interval -72.0 to -49.0
|
-38 percent change
Interval -56.0 to -12.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
ApoB: ApoB-100
|
-3 percent change
Interval -9.0 to 3.0
|
-5 percent change
Interval -11.0 to 1.0
|
-10 percent change
Interval -16.0 to -4.0
|
-9 percent change
Interval -15.0 to -1.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
ApoCIII
|
-6 percent change
Interval -22.0 to 14.0
|
-40 percent change
Interval -51.0 to -27.0
|
-61 percent change
Interval -68.0 to -52.0
|
-50 percent change
Interval -61.0 to -37.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
ApoA1
|
3 percent change
Interval -4.0 to 11.0
|
-9 percent change
Interval -15.0 to -2.0
|
-24 percent change
Interval -29.0 to -18.0
|
-12 percent change
Interval -19.0 to -4.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
FFA
|
-11 percent change
Interval -24.0 to 4.0
|
-12 percent change
Interval -25.0 to 3.0
|
-18 percent change
Interval -31.0 to -4.0
|
-11 percent change
Interval -27.0 to 8.0
|
|
Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point
Lp(a)
|
3 percent change
Interval -8.0 to 15.0
|
-4 percent change
Interval -15.0 to 8.0
|
-3 percent change
Interval -14.0 to 9.0
|
-1 percent change
Interval -14.0 to 13.0
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=16 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose at the Primary Analysis Time Point
|
-4.4 mg/dL
Interval -21.74 to 12.95
|
-21.6 mg/dL
Interval -40.05 to -3.17
|
9.4 mg/dL
Interval -9.53 to 28.4
|
-2.2 mg/dL
Interval -25.33 to 20.9
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=22 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=19 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Hemoglobin A1c (HbA1c) at the Primary Analysis Time Point
|
0.19 percentage of HbA1c
Interval -0.27 to 0.64
|
-0.09 percentage of HbA1c
Interval -0.56 to 0.37
|
0.26 percentage of HbA1c
Interval -0.22 to 0.75
|
0.35 percentage of HbA1c
Interval -0.18 to 0.87
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=16 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Fasting Insulin at the Primary Analysis Time Point
|
-0.10 milli-international units per liter
Interval -5.74 to 5.55
|
-1.48 milli-international units per liter
Interval -7.51 to 4.54
|
-0.23 milli-international units per liter
Interval -6.37 to 5.91
|
3.48 milli-international units per liter
Interval -3.94 to 10.9
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
HOMA-IR is a method used to quantify insulin resistance. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/mL) \* fasting plasma glucose (mmol/L)/22.5. A negative change from Baseline indicates improvement. An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=16 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in and HOMA-IR at the Primary Analysis Time Point
|
-0.119 index
Interval -3.47 to 3.24
|
-1.914 index
Interval -5.5 to 1.67
|
0.141 index
Interval -3.52 to 3.8
|
2.013 index
Interval -2.41 to 6.44
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=17 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Fructosamine at Primary Analysis Time Point
|
13.2 μmol/L
Interval -5.4 to 31.8
|
-10.0 μmol/L
Interval -29.34 to 9.4
|
1.8 μmol/L
Interval -17.92 to 21.44
|
15.1 μmol/L
Interval -7.74 to 38.04
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=17 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Glycated Albumin at the Primary Analysis Time Point
|
-0.0033 grams per deciliter (g/dL)
Interval -0.07 to 0.07
|
-0.0553 grams per deciliter (g/dL)
Interval -0.13 to 0.02
|
-0.0133 grams per deciliter (g/dL)
Interval -0.09 to 0.06
|
0.0280 grams per deciliter (g/dL)
Interval -0.06 to 0.12
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=25 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Weight at the Primary Analysis Time Point
|
-1.00 kg
Interval -2.19 to 0.18
|
-0.57 kg
Interval -1.76 to 0.62
|
-0.99 kg
Interval -2.15 to 0.17
|
-1.33 kg
Interval -2.57 to -0.09
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=25 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Primary Analysis Time Point
SBP
|
-1.66 millimeters of mercury (mmHg)
Interval -6.66 to 3.33
|
1.13 millimeters of mercury (mmHg)
Interval -4.07 to 6.34
|
0.42 millimeters of mercury (mmHg)
Interval -4.67 to 5.51
|
-3.29 millimeters of mercury (mmHg)
Interval -8.76 to 2.17
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Primary Analysis Time Point
DBP
|
-2.35 millimeters of mercury (mmHg)
Interval -5.71 to 1.0
|
1.75 millimeters of mercury (mmHg)
Interval -1.7 to 5.2
|
1.13 millimeters of mercury (mmHg)
Interval -2.26 to 4.52
|
-0.73 millimeters of mercury (mmHg)
Interval -4.35 to 2.88
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C6Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the percent change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=25 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Weight, SBP and DBP at Primary Analysis Time Point
Weight
|
-0.98 percent change
Interval -2.23 to 0.27
|
-0.40 percent change
Interval -1.66 to 0.85
|
-1.10 percent change
Interval -2.32 to 0.12
|
-1.38 percent change
Interval -2.69 to -0.07
|
|
Percent Change From Baseline in Weight, SBP and DBP at Primary Analysis Time Point
SBP
|
-0.55 percent change
Interval -4.57 to 3.46
|
1.80 percent change
Interval -2.38 to 5.98
|
0.68 percent change
Interval -3.41 to 4.77
|
-1.79 percent change
Interval -6.17 to 2.6
|
|
Percent Change From Baseline in Weight, SBP and DBP at Primary Analysis Time Point
DBP
|
-1.83 percent change
Interval -6.22 to 2.56
|
3.18 percent change
Interval -1.33 to 7.69
|
2.11 percent change
Interval -2.32 to 6.54
|
-0.13 percent change
Interval -4.85 to 4.6
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=22 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=19 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point
|
-1.69 percentage (Hepatic Fat Fraction)
Interval -4.09 to 0.71
|
-0.71 percentage (Hepatic Fat Fraction)
Interval -3.21 to 1.78
|
2.39 percentage (Hepatic Fat Fraction)
Interval -0.16 to 4.94
|
-0.12 percentage (Hepatic Fat Fraction)
Interval -2.87 to 2.64
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the percent change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=22 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=19 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point
|
-7.09 percent change
Interval -23.63 to 9.45
|
5.34 percent change
Interval -11.83 to 22.52
|
18.94 percent change
Interval 1.38 to 36.51
|
5.18 percent change
Interval -13.8 to 24.15
|
SECONDARY outcome
Timeframe: Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
The percentage of participants who achieved HFF ≤ 8% at the Primary Analysis Time Point was compared between each ISIS 703802 treatment group and pooled placebo group using a logistic regression model.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=22 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=19 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Percentage of Participants With HFF ≤ 8% by MRI-PDFF at the Primary Analysis Time Point
|
16.0 percentage of participants
|
8.7 percentage of participants
|
4.5 percentage of participants
|
15.8 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
The FLI was calculated by the following formula: FLI =(e0.953×loge\[triglycerides\]+0.139× Body Mass Index \[BMI\]+0.718×loge Gamma- Glutamyl Transferase \[GGT\]+0.053×waistcircumference-15.745)/ (1 + e0.953×loge\[triglycerides\]+0.139×BMI+0.718×loge \[GGT\]+0.053×waistcircumference-15.745) × 100. An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=24 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Fatty Liver Index (FLI) at the Primary Analysis Time Point
|
-3.50 index
Interval -8.21 to 1.22
|
-6.08 index
Interval -11.08 to -1.09
|
-9.21 index
Interval -13.99 to -4.44
|
-8.07 index
Interval -13.06 to -3.07
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=25 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at the Primary Analysis Time Point
ALT
|
-2.2 units per liter (U/L)
Interval -8.48 to 3.99
|
4.8 units per liter (U/L)
Interval -1.75 to 11.38
|
12.5 units per liter (U/L)
Interval 6.3 to 18.79
|
6.6 units per liter (U/L)
Interval -0.06 to 13.32
|
|
Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at the Primary Analysis Time Point
AST
|
-1.8 units per liter (U/L)
Interval -5.5 to 1.93
|
3.2 units per liter (U/L)
Interval -0.71 to 7.12
|
6.7 units per liter (U/L)
Interval 2.93 to 10.37
|
4.7 units per liter (U/L)
Interval 0.77 to 8.71
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=19 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Leptin at the Primary Analysis Time Point
|
0.95 μg/L
Interval -1.37 to 3.27
|
-0.24 μg/L
Interval -2.66 to 2.18
|
-0.57 μg/L
Interval -2.99 to 1.85
|
-3.23 μg/L
Interval -5.9 to -0.56
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=23 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=19 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Adiponectin at the Primary Analysis Time Point
|
0.20 milligrams per liter (mg/L)
Interval -0.2 to 0.6
|
0.05 milligrams per liter (mg/L)
Interval -0.37 to 0.48
|
-0.18 milligrams per liter (mg/L)
Interval -0.61 to 0.24
|
-0.18 milligrams per liter (mg/L)
Interval -0.65 to 0.29
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=23 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=20 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=19 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Subcutaneous Adipose Tissue (SAT) and Visceral Adipose Tissue (VAT) by Single Slice MRI at the Primary Analysis Timepoint
SAT
|
-25.61 mm^2
Interval -156.99 to 105.76
|
-8.55 mm^2
Interval -145.57 to 128.47
|
7.31 mm^2
Interval -139.08 to 153.7
|
-41.91 mm^2
Interval -192.12 to 108.29
|
|
Change From Baseline in Subcutaneous Adipose Tissue (SAT) and Visceral Adipose Tissue (VAT) by Single Slice MRI at the Primary Analysis Timepoint
VAT
|
14.83 mm^2
Interval -112.13 to 141.79
|
19.78 mm^2
Interval -109.07 to 148.63
|
-9.42 mm^2
Interval -149.27 to 130.42
|
36.85 mm^2
Interval -105.21 to 178.91
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=25 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=25 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Waist Circumference by Single Slice MRI at the Primary Analysis Timepoint
|
-2.25 cm
Interval -6.85 to 2.35
|
-2.14 cm
Interval -6.77 to 2.49
|
-2.95 cm
Interval -7.51 to 1.61
|
-0.59 cm
Interval -5.41 to 4.23
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=24 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=25 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Waist to Hip Ratio (WHR) at the Primary Analysis Timepoint
|
0.01 ratio
Interval -0.03 to 0.04
|
0.01 ratio
Interval -0.02 to 0.05
|
-0.01 ratio
Interval -0.04 to 0.02
|
0.01 ratio
Interval -0.03 to 0.05
|
SECONDARY outcome
Timeframe: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and CPopulation: FAS population included all participants who were randomized and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure
An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.
Outcome measures
| Measure |
Pooled Placebo
n=26 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=24 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=25 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=22 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Change From Baseline in Body Mass Index (BMI) at the Primary Analysis Timepoint
|
-0.27 kg/m^2
Interval -0.69 to 0.15
|
-0.17 kg/m^2
Interval -0.59 to 0.26
|
-0.37 kg/m^2
Interval -0.79 to 0.04
|
-0.50 kg/m^2
Interval -0.94 to -0.05
|
SECONDARY outcome
Timeframe: Up to 13 weeks post treatment period (up to 39 weeks)Population: Safety set included all participants who were randomized and received at least 1 dose of study drug.
An AE was defined as any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. TEAEs were defined as adverse events that occurred after the first administration of study drug.
Outcome measures
| Measure |
Pooled Placebo
n=27 Participants
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=26 Participants
Participants received ISIS 703802, 40 mg SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=26 Participants
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=26 Participants
Participants received ISIS 703802, 20 mg SC once every week for 26 doses.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
18 Participants
|
21 Participants
|
24 Participants
|
23 Participants
|
Adverse Events
Pooled Placebo
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Cohort B: ISIS 703802, 40 mg Q4W
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Cohort C: ISIS 703802, 80 mg Q4W
Serious events: 2 serious events
Other events: 20 other events
Deaths: 0 deaths
Cohort A: ISIS 703802, 20 mg QW
Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pooled Placebo
n=27 participants at risk
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=26 participants at risk
Participants received ISIS 703802, 40 milligrams (mg) SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=26 participants at risk
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=26 participants at risk
Participants received ISIS 703802, 20 mg once every week for 26 doses.
|
|---|---|---|---|---|
|
Infections and infestations
Actinomycosis
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Procedural complication
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Renal and urinary disorders
Nephrolithiasis
|
3.7%
1/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Pooled Placebo
n=27 participants at risk
Participants from each cohort received placebo at a dose-matched volume of study drug, SC.
|
Cohort B: ISIS 703802, 40 mg Q4W
n=26 participants at risk
Participants received ISIS 703802, 40 milligrams (mg) SC once every 4 weeks for 6 doses.
|
Cohort C: ISIS 703802, 80 mg Q4W
n=26 participants at risk
Participants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
|
Cohort A: ISIS 703802, 20 mg QW
n=26 participants at risk
Participants received ISIS 703802, 20 mg once every week for 26 doses.
|
|---|---|---|---|---|
|
General disorders
Injection site pruritus
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
30.8%
8/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Injection site erythema
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
23.1%
6/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
General disorders
Pyrexia
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
11.5%
3/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
11.5%
3/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
14.8%
4/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Sinusitis
|
3.7%
1/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.4%
2/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
11.5%
3/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
7.4%
2/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Infections and infestations
Vaginal infection
|
11.1%
3/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
3/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
11.5%
3/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
7.4%
2/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
11.5%
3/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Dyspepsia
|
7.4%
2/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Investigations
Blood glucose increased
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Investigations
Transaminases increased
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
11.5%
3/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.7%
1/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
7.4%
2/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
11.5%
3/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
7.7%
2/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
3.8%
1/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
|
Vascular disorders
Hypertension
|
7.4%
2/27 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
0.00%
0/26 • Up to 13 weeks post-treatment period (up to 39 weeks)
Safety population included all participants who were randomized and received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER