Trial Outcomes & Findings for Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (NCT NCT03156621)

NCT ID: NCT03156621

Last Updated: 2021-06-29

Results Overview

The percent change in LDL-C from baseline to week 12 is defined as: 100x (LDL-C value at week 12 - LDL-C value at baseline) / LDL-C value at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 69 participants
• Primary outcome timeframe: Baseline to Week 12
• Results posted on: 2021-06-29

Participant Flow

Participants were recruited from 27 centers in 13 countries around Europe, Asia, South Africa, and North America. A total of 85 participants were screened. Of those,16 were considered screen failures (mainly due to violations of inclusion/exclusion criteria).

Sixty-nine of the 85 participants were eligible and randomized in a 2:1 ratio to receive either alirocumab 150 mg SC Q2W or matching placebo. Randomization was stratified by LDL apheresis treatment status (on vs off treatment).

Participant milestones

Measure	Placebo in DBTP Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W
Double-Blind Treatment Period (DBTP) STARTED	24	45
Double-Blind Treatment Period (DBTP) COMPLETED	24	45
Double-Blind Treatment Period (DBTP) NOT COMPLETED	0	0
Open-Label Treatment Period (OLTP) STARTED	24	45
Open-Label Treatment Period (OLTP) COMPLETED	24	42
Open-Label Treatment Period (OLTP) NOT COMPLETED	0	3

Reasons for withdrawal

Measure	Placebo in DBTP Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W
Open-Label Treatment Period (OLTP) Adverse Event	0	2
Open-Label Treatment Period (OLTP) Withdrawal by Subject	0	1

Baseline Characteristics

Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

Baseline characteristics by cohort

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Total n=69 Participants Total of all reporting groups
Age, Continuous	45.4 Years STANDARD_DEVIATION 15.80 • n=5 Participants	42.3 Years STANDARD_DEVIATION 14.13 • n=7 Participants	43.4 Years STANDARD_DEVIATION 14.69 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	24 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	21 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	43 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants	36 Participants n=7 Participants	54 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Low-density lipoprotein cholesterol (LDL-C)	259.6 milligram/deciLiter (mg/dL) STANDARD_DEVIATION 175.75 • n=5 Participants	295.0 milligram/deciLiter (mg/dL) STANDARD_DEVIATION 154.59 • n=7 Participants	282.7 milligram/deciLiter (mg/dL) STANDARD_DEVIATION 161.86 • n=5 Participants
Non-high-density lipoprotein cholesterol (Non-HDL-C)	282.0 mg/dL STANDARD_DEVIATION 177.41 • n=5 Participants	320.5 mg/dL STANDARD_DEVIATION 160.36 • n=7 Participants	307.1 mg/dL STANDARD_DEVIATION 166.22 • n=5 Participants
Total-cholesterol (Total-C)	325.1 mg/dL STANDARD_DEVIATION 171.57 • n=5 Participants	364.3 mg/dL STANDARD_DEVIATION 157.30 • n=7 Participants	350.7 mg/dL STANDARD_DEVIATION 162.24 • n=5 Participants
High-density lipoprotein cholesterol (HDL-C)	43.2 mg/dL STANDARD_DEVIATION 11.96 • n=5 Participants	43.8 mg/dL STANDARD_DEVIATION 14.78 • n=7 Participants	43.6 mg/dL STANDARD_DEVIATION 13.78 • n=5 Participants
Fasting triglycerides (TG)	111.7 mg/dL STANDARD_DEVIATION 77.97 • n=5 Participants	128.0 mg/dL STANDARD_DEVIATION 74.34 • n=7 Participants	122.3 mg/dL STANDARD_DEVIATION 75.45 • n=5 Participants
Lipoprotein(a) [Lp(a)]	40.0 mg/dL STANDARD_DEVIATION 36.41 • n=5 Participants	42.9 mg/dL STANDARD_DEVIATION 36.34 • n=7 Participants	41.9 mg/dL STANDARD_DEVIATION 36.12 • n=5 Participants
Apolipoprotein-B (Apo-B)	175.0 mg/dL STANDARD_DEVIATION 95.12 • n=5 Participants	193.3 mg/dL STANDARD_DEVIATION 87.59 • n=7 Participants	186.9 mg/dL STANDARD_DEVIATION 90.01 • n=5 Participants
Apolipoprotein-A1 (Apo-A1)	124.8 mg/dL STANDARD_DEVIATION 24.59 • n=5 Participants	125.6 mg/dL STANDARD_DEVIATION 28.57 • n=7 Participants	125.3 mg/dL STANDARD_DEVIATION 27.07 • n=5 Participants
Apo-B/Apo-A1	1.590 ratio STANDARD_DEVIATION 1.4746 • n=5 Participants	1.635 ratio STANDARD_DEVIATION 0.8693 • n=7 Participants	1.619 ratio STANDARD_DEVIATION 1.1067 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: ITT estimand (All randomized participants who had at least 1 measurement value for LDL-C before the first dose of double blind investigational study drug)

The percent change in LDL-C from baseline to week 12 is defined as: 100x (LDL-C value at week 12 - LDL-C value at baseline) / LDL-C value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)	8.6 Percentage of change Standard Error 6.3	-26.9 Percentage of change Standard Error 4.6	—

SECONDARY outcome

Timeframe: Baseline to Week 12

ITT estimand; The percent change in Apo B from baseline to week 12 is defined as: 100x (Apo B value at week 12 - Apo B value at baseline) / Apo B value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand)	7.2 Percentage of change Standard Error 5.0	-22.5 Percentage of change Standard Error 3.7	—

SECONDARY outcome

Timeframe: Baseline to Week 12

ITT estimand; The percent change in non-HDL-C from baseline to week 12 is defined as: 100x (non-HDL-C value at week 12 - non-HDL-C value at baseline) / non-HDL-C value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12	8.0 Percentage of change Standard Error 5.9	-24.8 Percentage of change Standard Error 4.3	—

SECONDARY outcome

Timeframe: Baseline to Week 12

ITT estimand; The percent change in TC from baseline to week 12 is defined as: 100x (TC value at week 12 - TC value at baseline) / TC value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Total Cholesterol (TC) From Baseline to Week 12	6.6 Percentage of change Standard Error 5.0	-19.8 Percentage of change Standard Error 3.7	—

SECONDARY outcome

Timeframe: At Week 12

ITT estimand

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percentage of Participants With ≥15% Reduction in LDL-C at Week 12	12.5 Percentage of participants	61.9 Percentage of participants	—

SECONDARY outcome

Timeframe: At Week 12

ITT estimand

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percentage of Participants With ≥30% Reduction in LDL-C at Week 12	4.2 Percentage of participants	57.1 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Week 12

ITT estimand; The percent change in Lp(a) from baseline to week 12 is defined as: 100x (Lp(a) value at week 12 - Lp(a) value at baseline) / Lp(a) value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12	8.8 Percentage of change Standard Error 5.4	-19.6 Percentage of change Standard Error 4.0	—

SECONDARY outcome

Timeframe: At Week 12

ITT estimand

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percentage of Participants With ≥50% Reduction in LDL-C at Week 12	0 Percentage of participants	26.7 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Week 12

ITT estimand; The percent change in HDL-C from baseline to week 12 is defined as: 100x (HDL-C value at week 12 - HDL-C value at baseline) / HDL-C value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis	2.7 Percentage of change Standard Error 3.1	6.3 Percentage of change Standard Error 2.3	—

SECONDARY outcome

Timeframe: Baseline to Week 12

ITT estimand; The percent change in TG from baseline to week 12 is defined as: 100x (TG value at week 12 - TG value at baseline) / TG value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12	3.9 Percentage of change Standard Error 5.7	-7.4 Percentage of change Standard Error 4.2	—

SECONDARY outcome

Timeframe: Baseline to Week 12

ITT estimand; The percent change in Apo A-1 from baseline to week 12 is defined as: 100x (Apo A-1 value at week 12 - Apo A-1 value at baseline) / Apo A-1 value at baseline.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis	1.4 Percentage of change Standard Error 2.9	5.0 Percentage of change Standard Error 2.1	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for LDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)	8.6 Percentage of change Standard Error 6.3	-26.9 Percentage of change Standard Error 4.6	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for Apo B from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label nvestigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand)	7.2 Percentage of change Standard Error 5.0	-22.5 Percentage of change Standard Error 3.7	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for non-HDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand)	8.0 Percentage of change Standard Error 5.9	-24.8 Percentage of change Standard Error 4.3	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for TC from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in TC From Baseline to Week 12 (On-treatment Estimand)	6.6 Percentage of change Standard Error 5.0	-19.8 Percentage of change Standard Error 3.7	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for LP(a) from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)	8.8 Percentage of change Standard Error 5.4	-19.6 Percentage of change Standard Error 4.0	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for HDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)	2.7 Percentage of change Standard Error 3.1	6.3 Percentage of change Standard Error 2.3	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for fasting TG from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)	3.9 Percentage of change Standard Error 5.7	-7.4 Percentage of change Standard Error 4.2	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Percent change for Apo A-1 from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand)	1.4 Percentage of change Standard Error 2.9	5.0 Percentage of change Standard Error 2.1	—

SECONDARY outcome

Timeframe: At Week 12

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) ≥ 15%	12.5 Percentage of participants	61.9 Percentage of participants	—
Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) ≥ 30%	4.2 Percentage of participants	57.1 Percentage of participants	—
Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) ≥ 50%	0 Percentage of participants	26.7 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Ratio of Apo B/Apo A1 at week 12 minus ratio of Apo B/Apo A1 at baseline

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand)	0.0 Ratio of change Standard Error 0.1	-0.3 Ratio of change Standard Error 0.1	—

SECONDARY outcome

Timeframe: 26 weeks

Population: Here 'n' = number of evaluable participants at this time point

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=44 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time	1 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Baseline to week 32 (End of Study)

All AEs will be recorded from time of informed consent to end of study. Only treatment-emergent adverse events (TEAE) will be reported. Double-blind TEAE observation period is defined as time from first dose of double-blind study drug to last dose of double-blind study drug +70 days, or up to day before first dose of open-label study drug administration, whichever is earlier. Open-label TEAE observation period is defined as time from first open-label study treatment administration to last open-label study treatment administration +70 days.

Outcome measures

Measure	Placebo in DBTP n=24 Participants Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W n=45 Participants Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	Alirocumab 150 mg SC Q2W in OLTP n=69 Participants Participants who received at least 1 dose or part of a dose of open-label investigational study drug alirocumab in OLTP
Number of Participants With Adverse Events (AEs) Participants with any TEAE	12 Participants	20 Participants	24 Participants
Number of Participants With Adverse Events (AEs) Participants with TEAE Serious Adverse Event (SAE)	0 Participants	0 Participants	1 Participants

Adverse Events

DB Placebo (DBTP)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

DB Alirocumab 150 Q2W (DBTP)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

DB Placebo (OLTP)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

DB Alirocumab 150 Q2W (OLTP)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	DB Placebo (DBTP) n=24 participants at risk Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period.	DB Alirocumab 150 Q2W (DBTP) n=45 participants at risk Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period.	DB Placebo (OLTP) n=24 participants at risk Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	DB Alirocumab 150 Q2W (OLTP) n=45 participants at risk Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/24 • Baseline (Day 1) to end of study (Day 225)	0.00% 0/45 • Baseline (Day 1) to end of study (Day 225)	0.00% 0/24 • Baseline (Day 1) to end of study (Day 225)	2.2% 1/45 • Number of events 1 • Baseline (Day 1) to end of study (Day 225)

Other adverse events

Measure	DB Placebo (DBTP) n=24 participants at risk Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period.	DB Alirocumab 150 Q2W (DBTP) n=45 participants at risk Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period.	DB Placebo (OLTP) n=24 participants at risk Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W	DB Alirocumab 150 Q2W (OLTP) n=45 participants at risk Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W
Gastrointestinal disorders Diarrhoea	0.00% 0/24 • Baseline (Day 1) to end of study (Day 225)	6.7% 3/45 • Number of events 3 • Baseline (Day 1) to end of study (Day 225)	0.00% 0/24 • Baseline (Day 1) to end of study (Day 225)	2.2% 1/45 • Number of events 1 • Baseline (Day 1) to end of study (Day 225)
Infections and infestations Nasopharyngitis	0.00% 0/24 • Baseline (Day 1) to end of study (Day 225)	4.4% 2/45 • Number of events 3 • Baseline (Day 1) to end of study (Day 225)	4.2% 1/24 • Number of events 1 • Baseline (Day 1) to end of study (Day 225)	6.7% 3/45 • Number of events 4 • Baseline (Day 1) to end of study (Day 225)
Infections and infestations Upper respiratory tract infection	8.3% 2/24 • Number of events 3 • Baseline (Day 1) to end of study (Day 225)	4.4% 2/45 • Number of events 2 • Baseline (Day 1) to end of study (Day 225)	0.00% 0/24 • Baseline (Day 1) to end of study (Day 225)	0.00% 0/45 • Baseline (Day 1) to end of study (Day 225)
Nervous system disorders Headache	8.3% 2/24 • Number of events 8 • Baseline (Day 1) to end of study (Day 225)	4.4% 2/45 • Number of events 2 • Baseline (Day 1) to end of study (Day 225)	4.2% 1/24 • Number of events 2 • Baseline (Day 1) to end of study (Day 225)	2.2% 1/45 • Number of events 1 • Baseline (Day 1) to end of study (Day 225)

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844 734 6643

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER