Trial Outcomes & Findings for Phase 2 Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Chylomicronemia Syndrome (FCS) (NCT NCT03360747)
NCT ID: NCT03360747
Last Updated: 2021-01-07
Results Overview
Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
COMPLETED
PHASE2
3 participants
Baseline to Month 3
2021-01-07
Participant Flow
Participants took part in the study at 1 study site in Canada from 21-December-2017 to 4-September-2018.
A total of 4 participants were screened, 3 of whom were enrolled and treated with at least one dose of study drug and were included in the analysis. This study consisted of up to an 8-week screening period, a 13-week treatment period and a 13-week follow-up (post-treatment evaluation) period.
Participant milestones
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
Participants received a subcutaneous (SC) injection of AKCEA-ANGPTL3-LRx, 20 milligrams (mg), weekly (QW) for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Overall Study
STARTED
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3
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Overall Study
COMPLETED
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2
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
Participants received a subcutaneous (SC) injection of AKCEA-ANGPTL3-LRx, 20 milligrams (mg), weekly (QW) for 13-weeks of treatment period. Participants were followed up to Week 26.
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Overall Study
Voluntary Withdrawal
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1
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Baseline Characteristics
Phase 2 Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Chylomicronemia Syndrome (FCS)
Baseline characteristics by cohort
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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Age, Continuous
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51.0 years
STANDARD_DEVIATION 15.72 • n=5 Participants
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Sex: Female, Male
Female
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1 Participants
n=5 Participants
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Sex: Female, Male
Male
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2 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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3 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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3 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Fasting Triglycerides (TG)
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2299.50 milligrams per deciliter (mg/dL)
STANDARD_DEVIATION 961.139 • n=5 Participants
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Fasting Angiopoietin-Like 3 (ANGPTL3)
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62.433 nanograms per milliliter (ng/mL)
STANDARD_DEVIATION 8.9030 • n=5 Participants
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Fasting Total Cholesterol (TC)
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316.50 mg/dL
STANDARD_DEVIATION 81.957 • n=5 Participants
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Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C)
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301.17 mg/dL
STANDARD_DEVIATION 82.791 • n=5 Participants
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Fasting Apolipoprotein B (ApoB)
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72.65 mg/dL
STANDARD_DEVIATION 9.406 • n=5 Participants
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Fasting High Density Lipoprotein Cholesterol (HDL-C)
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15.3 mg/dL
STANDARD_DEVIATION 1.15 • n=5 Participants
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Fasting Apolipoprotein A-1 (ApoA-1)
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94.7 mg/dL
STANDARD_DEVIATION 7.51 • n=5 Participants
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Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C)
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272.67 mg/dL
STANDARD_DEVIATION 89.326 • n=5 Participants
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Fasting Low Density Lipoprotein Cholesterol (LDL-C)
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28.50 mg/dL
STANDARD_DEVIATION 6.946 • n=5 Participants
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Maximum Postprandial Triglycerides
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2454.81 mg/dL
STANDARD_DEVIATION 1019.963 • n=5 Participants
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PRIMARY outcome
Timeframe: Baseline to Month 3Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG)
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-550.00 mg/dL
Standard Deviation 431.471
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PRIMARY outcome
Timeframe: Baseline to Month 3Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)
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-32.83 percent change
Standard Deviation 31.994
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SECONDARY outcome
Timeframe: Baseline to Month 3Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3)
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-31.983 ng/mL
Standard Deviation 5.4773
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SECONDARY outcome
Timeframe: Baseline to Month 3Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3)
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-51.249 percent change
Standard Deviation 4.9093
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SECONDARY outcome
Timeframe: Month 3Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Fasting lipid and lipoprotein measurements included non-HDL-C, ApoB, HDL-C, ApoA-1, VLDL-C and LDL-C. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Fasting Lipid and Lipoprotein Measurements at Month 3
Non-HDL-C
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217.33 mg/dL
Standard Deviation 119.618
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Fasting Lipid and Lipoprotein Measurements at Month 3
ApoB
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64.53 mg/dL
Standard Deviation 4.899
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Fasting Lipid and Lipoprotein Measurements at Month 3
HDL-C
|
13.0 mg/dL
Standard Deviation 1.00
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Fasting Lipid and Lipoprotein Measurements at Month 3
ApoA-1
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77.3 mg/dL
Standard Deviation 6.03
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Fasting Lipid and Lipoprotein Measurements at Month 3
VLDL-C
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190.17 mg/dL
Standard Deviation 128.861
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Fasting Lipid and Lipoprotein Measurements at Month 3
LDL-C
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27.17 mg/dL
Standard Deviation 10.324
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SECONDARY outcome
Timeframe: Baseline to Month 3Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Other fasting lipid measurements included total cholesterol (TC), non-HDL-C, ApoB, HDL-C, ApoA-1, VLDL-C, and LDL-C. Baseline was defined as average of Day 1 predose fasting assessment and last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Absolute Change From Baseline to Month 3 in TC
|
-86.17 mg/dL
Standard Deviation 48.581
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Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Absolute Change From Baseline to Month 3:Non-HDL-C
|
-83.83 mg/dL
Standard Deviation 48.235
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Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Absolute Change From Baseline to Month 3 in ApoB
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-8.12 mg/dL
Standard Deviation 5.352
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Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Absolute Change From Baseline to Month 3 in HDL-C
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-2.3 mg/dL
Standard Deviation 0.58
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Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Absolute Change From Baseline to Month 3 in ApoA-1
|
-17.3 mg/dL
Standard Deviation 11.93
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Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Absolute Change From Baseline to Month 3 in VLDL-C
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-82.50 mg/dL
Standard Deviation 51.215
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Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Absolute Change From Baseline to Month 3 in LDL-C
|
-1.33 mg/dL
Standard Deviation 3.753
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SECONDARY outcome
Timeframe: Baseline to Month 3Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Other fasting lipid measurements included TC, non-HDL-C, ApoB, HDL-C, ApoA-1, VLDL-C, and LDL-C. Baseline was defined as average of Day 1 predose fasting assessment and last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
% Change From Baseline to Month 3 in TC
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-30.39 percent change
Standard Deviation 20.436
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Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
% Change From Baseline to Month 3 in Non-HDL-C
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-31.49 percent change
Standard Deviation 21.832
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Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
% Change From Baseline to Month 3 in ApoB
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-10.73 percent change
Standard Deviation 6.021
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Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
% Change From Baseline to Month 3 in HDL-C
|
-15.2 percent change
Standard Deviation 3.22
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Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
% Change From Baseline to Month 3 in ApoA-1
|
-17.8 percent change
Standard Deviation 10.97
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Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
% Change From Baseline to Month 3 in VLDL-C
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-36.03 percent change
Standard Deviation 28.044
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Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
% Change From Baseline to Month 3 in LDL-C
|
-6.47 percent change
Standard Deviation 13.426
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SECONDARY outcome
Timeframe: Baseline to Day 92Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
Participants consumed standardized pre-cooked meals (lunches and dinners and instructions for breakfasts and snacks) for 2 days prior to the postprandial assessments. Change from Baseline to Day 92 in maximum postprandial TG was assessed.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=2 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG)
|
-338.0 mg/dL
Standard Deviation 38.22
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SECONDARY outcome
Timeframe: Days 1, 29, 57 and 92Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Number of Participants Who Experienced Abdominal Pain During the Treatment Period
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1 Participants
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SECONDARY outcome
Timeframe: From time of informed consent to end of follow-up period (Up to Week 26)Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
An adverse event (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 is considered related to the investigational drug product. A TEAE was defined as any AE starting on or after the first dose of the study drug.
Outcome measures
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 Participants
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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|---|---|
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Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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3 Participants
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Adverse Events
AKCEA-ANGPTL3-LRx 20 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AKCEA-ANGPTL3-LRx 20 mg
n=3 participants at risk
Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26.
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General disorders
Asthenia
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33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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General disorders
Influenza like illness
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33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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Musculoskeletal and connective tissue disorders
Back pain
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33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
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33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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Nervous system disorders
Headache
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66.7%
2/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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Ear and labyrinth disorders
Vertigo positional
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33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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Infections and infestations
Influenza
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33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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Metabolism and nutrition disorders
Hyperlipidaemia
|
33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
|
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Psychiatric disorders
Loss of libido
|
33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
|
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Psychiatric disorders
Mood swings
|
33.3%
1/3 • From time of informed consent to end of follow-up period (Up to Week 26).
Safety set included all participants who were enrolled and received at least 1 dose of study drug.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60