CompletedNCT03156621ODYSSEY HoFHUpdated Jun 29, 2021Results posted

Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

A Phase 3 interventional study of Alirocumab and Placebo in Homozygous Familial Hypercholesterolemia, sponsored by Regeneron Pharmaceuticals. Completed at 28 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-29.

Sponsored by Regeneron Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 69
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

The primary objective of the study is to demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) with alirocumab subcutaneous (SC) every 2 weeks (Q2W) in comparison to placebo after 12 weeks of treatment.

The secondary objectives of the study are:

To evaluate the effect of alirocumab Q2W on other lipid parameters (ie, apolipoprotein [Apo] A-1 and B, non-high-density lipoprotein cholesterol [non-HDL-C], total-cholesterol [TC], proportion of participants with 15%, 30%, and 50% LDL-C reductions, Lp(a), HDL-C, triglycerides [TG]) in participants with HoFH
To evaluate the safety and tolerability of alirocumab SC Q2W in participants with HoFH
To assess the pharmacokinetics of alirocumab SC Q2W in participants with HoFH
To assess the potential development of anti-drug (alirocumab) antibodies

Conditions studied

Homozygous Familial Hypercholesterolemia

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In context

Hyperlipoproteinemia Type II

245 studies on the registry are indexed under Hyperlipoproteinemia Type II; 52 are open to participants now.

This study's enrollment of 69 is below the median of 86 across 170 interventional studies indexed under Hyperlipoproteinemia Type II.

Browse Hyperlipoproteinemia Type II studies →

Lead sponsor

Regeneron Pharmaceuticals is the lead sponsor of 400 studies on the registry; 91 are open to participants now.

Of its 120 completed or terminated interventional studies of FDA-regulated products, 77 (64%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Note: The information listed below is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial, therefore not all inclusion/exclusion criteria are listed.

Key Inclusion Criteria

Diagnosis of HoFH by at least 1 of the following genotype or clinical criteria (all patients on LDL apheresis must be diagnosed based on genotype):
1. Documented homozygous or compound heterozygous mutations in both low-density lipoprotein receptor (LDLR) alleles
2. Presence of homozygous or compound heterozygous mutations in Apo B, PCSK9 or LDL receptor adaptor protein 1 (LDLRAP1)
3. Presence of double heterozygous mutations, i.e, mutations on different genes in the LDLR, Apo B or PCSK9 alleles
4. Untreated TC >500 mg/dL (12.93 mmol/L) and TG \<300 mg/dL (3.39 mmol/L) AND Both parents with history of TC >250 mg/dL (6.46 mmol/L) OR cutaneous or tendinous xanthoma before age 10
Receiving a stable dose of a statin at the screening visit (documentation if statin ineffective or patient unable to tolerate statin)
If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly (every 7 days) or every other week (every 14 days) schedule or stable settings for at least 8 weeks

Key Exclusion Criteria:

Documented evidence of a null mutation in both LDLR alleles
Use of a PCSK9 inhibitor within 10 weeks from screening visit
Background medical lipid modifying therapy (LMT) that has not been stable for at least 4 weeks (6 weeks for fibrates, 24 weeks for mipomersen, 12 weeks for maximum tolerated dose of lomitapide) before the screening visit.
LDL apheresis schedule/apheresis settings that have not been stable for at least 8 weeks before the screening visit or an apheresis schedule/settings that is not anticipated to be stable over the next 24 weeks.
Use of nutraceuticals or over-the-counter (OTC) therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit or between the screening and randomization visits.
Chronic use of systemic corticosteroids, unless on a stable regimen of 10 mg daily prednisone equivalent or less for at least 6 weeks prior to randomization. Note: topical, intra-articular, nasal, inhaled and ophthalmic steroid therapies are not considered as 'systemic' and are allowed
Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at the screening visit (1 repeat measurement is allowed).
LDL-C level \<70 mg/dL (1.81 mmol/L) at the screening visit
History of a myocardial infarction (MI), unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention , uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 69 participants (actual)

Study arms

Experimental
Alirocumab SC Q2W
Alirocumab 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, participants will receive open-label alirocumab SC Q2W
Drug: Alirocumab
Experimental
Placebo SC Q2W
Matching placebo SC Q2W from baseline through week 10 during the double-blind treatment period Starting at week 12, and continuing through week 22, participants will receive open-label alirocumab SC Q2W
Drug: Alirocumab · Drug: Placebo

Interventions

DrugAlirocumab
Alirocumab SC Q2W
Also known as: PRALUENT®, REGN727, SAR236553
DrugPlacebo
Matching placebo SC Q2W

What researchers measure

Primary outcomes

Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)
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.
Time frame: Baseline to Week 12

Secondary outcomes

Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From 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.
Time frame: Baseline to Week 12
Percent Change in Total Cholesterol (TC) From 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.
Time frame: Baseline to Week 12
Percentage of Participants With ≥15% Reduction in LDL-C at Week 12
ITT estimand
Time frame: At Week 12
Percentage of Participants With ≥30% Reduction in LDL-C at Week 12
ITT estimand
Time frame: At Week 12
Percent Change in Lipoprotein(a) [Lp(a)] From 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.
Time frame: Baseline to Week 12
Percentage of Participants With ≥50% Reduction in LDL-C at Week 12
ITT estimand
Time frame: At Week 12
Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis
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.
Time frame: Baseline to Week 12
Percent Change in Fasting Triglycerides (TG) From 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.
Time frame: Baseline to Week 12
Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis
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.
Time frame: Baseline to Week 12
Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in TC From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand)
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.
Time frame: Baseline to Week 12
Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand)
Time frame: At Week 12
Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand)
Ratio of Apo B/Apo A1 at week 12 minus ratio of Apo B/Apo A1 at baseline
Time frame: Baseline to Week 12
Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time
Time frame: 26 weeks
Number of Participants With Adverse Events (AEs)
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.
Time frame: Baseline to week 32 (End of Study)

Results

Posted Jun 29, 2021

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).

Double-Blind Treatment Period (DBTP)

Participant flow — Double-Blind Treatment Period (DBTP)
Milestone	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Started	24	45
Completed	24	45
Not completed	0	0

Open-Label Treatment Period (OLTP)

Participant flow — Open-Label Treatment Period (OLTP)
Milestone	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Started	24	45
Completed	24	42
Not completed	0	3
Withdrew: Adverse event	0	2
Withdrew: Withdrawal by subject	0	1

Outcome measures

PrimaryPercent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)	8.6 ± 6.3	-26.9 ± 4.6

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · MMRM · p = <0.0001 (P-value taken from MMRM (mixed-effect model with repeated measures) analysis) · Least squares (ls) mean difference: -35.6 · 95% CI -51.2 to -19.9p-value vs Placebo

SecondaryPercent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand)	7.2 ± 5.0	-22.5 ± 3.7

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · MMRM · p = < 0.0001 (p-value taken from MMRM (mixed-effect model with repeated measures) analysis) · Least squares (ls) mean difference: -29.8 · 95% CI -42.3 to -17.3

SecondaryPercent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From 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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12	8.0 ± 5.9	-24.8 ± 4.3

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · MMRM · p = < 0.0001 (P-value taken from MMRM (mixed-effect model with repeated measures) analysis) · Least squares (ls) mean difference: -32.9 · 95% CI -47.6 to -18.2

SecondaryPercent Change in Total Cholesterol (TC) From 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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Total Cholesterol (TC) From Baseline to Week 12
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Total Cholesterol (TC) From Baseline to Week 12	6.6 ± 5.0	-19.8 ± 3.7

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · MMRM · p = < 0.0001 (P-value taken from MMRM (mixed-effect model with repeated measures) analysis.) · Least squares (ls) mean difference: -26.5 · 95% CI -38.9 to -14.0

SecondaryPercentage of Participants With ≥15% Reduction in LDL-C at Week 12

ITT estimand

Time frame:: At Week 12
Reported as:: Number · Percentage of participants

Percentage of Participants With ≥15% Reduction in LDL-C at Week 12
Percentage of participants	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percentage of Participants With ≥15% Reduction in LDL-C at Week 12	12.5	61.9

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Regression, Logistic · p = = 0.0004 · Odds ratio, log: 12.2 · 95% CI 3.1 to 48.8

SecondaryPercentage of Participants With ≥30% Reduction in LDL-C at Week 12

ITT estimand

Time frame:: At Week 12
Reported as:: Number · Percentage of participants

Percentage of Participants With ≥30% Reduction in LDL-C at Week 12
Percentage of participants	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percentage of Participants With ≥30% Reduction in LDL-C at Week 12	4.2	57.1

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Regression, Logistic · p = = 0.0010 · Odds ratio, log: 36.5 · 95% CI 4.3 to 308.9

SecondaryPercent Change in Lipoprotein(a) [Lp(a)] From 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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12	8.8 ± 5.4	-19.6 ± 4.0

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Regression model · p = < 0.0001 · Mean difference (final values): -28.4 · 95% CI -41.5 to -15.2

SecondaryPercentage of Participants With ≥50% Reduction in LDL-C at Week 12

ITT estimand

Time frame:: At Week 12
Reported as:: Number · Percentage of participants

Percentage of Participants With ≥50% Reduction in LDL-C at Week 12
Percentage of participants	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percentage of Participants With ≥50% Reduction in LDL-C at Week 12	0	26.7

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Exact Conditional Logistic Regression · p = = 0.0017 · Odds ratio (or): 17.7

SecondaryPercent Change in HDL-C From Baseline to Week 12 - ITT Analysis

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis	2.7 ± 3.1	6.3 ± 2.3

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · MMRM · p = = 0.3541 (P-value taken from MMRM (mixed-effect model with repeated measures) analysis.) · Least squares (ls) mean difference: 3.6 · 95% CI -4.1 to 11.3

SecondaryPercent Change in Fasting Triglycerides (TG) From 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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12	3.9 ± 5.7	-7.4 ± 4.2

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Mean difference (final values): -11.3 · 95% CI -25.2 to 2.6

SecondaryPercent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis	1.4 ± 2.9	5.0 ± 2.1

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: 3.6 · 95% CI -3.6 to 10.7

SecondaryPercent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)	8.6 ± 6.3	-26.9 ± 4.6

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: -35.6 · 95% CI -51.2 to -19.9

SecondaryPercent Change in Apo B From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand)	7.2 ± 5.0	-22.5 ± 3.7

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: -29.8 · 95% CI -43.3 to -17.3

SecondaryPercent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand)	8.0 ± 5.9	-24.8 ± 4.3

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: -32.9 · 95% CI -47.6 to -18.2

SecondaryPercent Change in TC From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in TC From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in TC From Baseline to Week 12 (On-treatment Estimand)	6.6 ± 5.0	-19.8 ± 3.7

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: -26.5 · 95% CI -28.9 to -14.0

SecondaryPercent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)	8.8 ± 5.4	-19.6 ± 4.0

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Mean difference (final values): -28.4 · 95% CI -41.5 to -15.2

SecondaryPercent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)	2.7 ± 3.1	6.3 ± 2.3

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: 3.6 · 95% CI -4.1 to 11.3

SecondaryPercent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)	3.9 ± 5.7	-7.4 ± 4.2

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Mean difference (final values): -11.3 · 95% CI -25.2 to 2.6

SecondaryPercent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand)

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.

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Percentage of change

Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand)
Percentage of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand)	1.4 ± 2.9	5.0 ± 2.1

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: 3.6 · 95% CI -3.6 to 10.7

SecondaryPercentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand)

Time frame:: At Week 12
Reported as:: Number · Percentage of participants

Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand)
Percentage of participants	Placebo in DBTP	Alirocumab 150 mg SC Q2W
≥ 15%	12.5	61.9
≥ 30%	4.2	57.1
≥ 50%	0	26.7

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Odds ratio (or): 12.2 · 95% CI 3.1 to 48.8
Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Odds ratio (or): 36.5 · 95% CI 4.3 to 308.9
Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Odds ratio (or): 17.7

SecondaryAbsolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand)

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

Time frame:: Baseline to Week 12
Reported as:: Least squares mean · Ratio of change

Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand)
Ratio of change	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand)	0.0 ± 0.1	-0.3 ± 0.1

Statistical analysis

Placebo in DBTP vs Alirocumab 150 mg SC Q2W · Least squares (ls) mean difference: -0.3 · 95% CI -0.6 to -0.1

SecondaryNumber of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time

Time frame:: 26 weeks
Reported as:: Number · Participants

Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time
Participants	Placebo in DBTP	Alirocumab 150 mg SC Q2W
Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time	1	1

SecondaryNumber of Participants With Adverse Events (AEs)

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.

Time frame:: Baseline to week 32 (End of Study)
Reported as:: Number · Participants

Number of Participants With Adverse Events (AEs)
Participants	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Alirocumab 150 mg SC Q2W in OLTP
Participants with any TEAE	12	20	24
Participants with TEAE Serious Adverse Event (SAE)	0	0	1

Adverse events

Collected over Baseline (Day 1) to end of study (Day 225). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
DB Placebo (DBTP)	0/24 (0%)	0/24 (0%)	4/24 (16.7%)
DB Alirocumab 150 Q2W (DBTP)	0/45 (0%)	0/45 (0%)	8/45 (17.8%)
DB Placebo (OLTP)	0/24 (0%)	0/24 (0%)	2/24 (8.3%)
DB Alirocumab 150 Q2W (OLTP)	0/45 (0%)	1/45 (2.2%)	4/45 (8.9%)

Most frequent serious events

Most frequent serious events
Event	DB Placebo (DBTP)	DB Alirocumab 150 Q2W (DBTP)	DB Placebo (OLTP)	DB Alirocumab 150 Q2W (OLTP)
ArthralgiaMusculoskeletal and connective tissue disorders	0/24	0/45	0/24	1/45

Most frequent other events

Most frequent other events
Event	DB Placebo (DBTP)	DB Alirocumab 150 Q2W (DBTP)	DB Placebo (OLTP)	DB Alirocumab 150 Q2W (OLTP)
Upper respiratory tract infectionInfections and infestations	2/24	2/45	0/24	0/45
HeadacheNervous system disorders	2/24	2/45	1/24	1/45
DiarrhoeaGastrointestinal disorders	0/24	3/45	0/24	1/45
NasopharyngitisInfections and infestations	0/24	2/45	1/24	3/45

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
Mean	45.4 ± 15.80	42.3 ± 14.13	43.4 ± 14.69

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
Female	11	24	35
Male	13	21	34

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
Hispanic or Latino	0	2	2
Not Hispanic or Latino	24	43	67
Unknown or Not Reported	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
White	18	36	54
Black or African American	0	2	2
Asian	5	7	12
American Indian or Alaska Native	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Other	1	0	1

Low-density lipoprotein cholesterol (LDL-C)
Low-density lipoprotein cholesterol (LDL-C)(milligram/deciLiter (mg/dL))	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
Mean	259.6 ± 175.75	295.0 ± 154.59	282.7 ± 161.86

Non-high-density lipoprotein cholesterol (Non-HDL-C)
Non-high-density lipoprotein cholesterol (Non-HDL-C)(mg/dL)	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
Mean	282.0 ± 177.41	320.5 ± 160.36	307.1 ± 166.22

Total-cholesterol (Total-C)
Total-cholesterol (Total-C)(mg/dL)	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
Mean	325.1 ± 171.57	364.3 ± 157.30	350.7 ± 162.24

High-density lipoprotein cholesterol (HDL-C)
High-density lipoprotein cholesterol (HDL-C)(mg/dL)	Placebo in DBTP	Alirocumab 150 mg SC Q2W	Total
Mean	43.2 ± 11.96	43.8 ± 14.78	43.6 ± 13.78

5 further baseline measures are reported on the registry.

Study locations

28 sites

Regeneron Research Site
Boca Raton, Florida 33434, United States
Regeneron Research Site
New York, New York 10029, United States
Regeneron Research Site
Cincinnati, Ohio 45227, United States
Regeneron Study Site
Dallas, Texas 78226, United States
Regeneron Research Site
Innsbruck, Tirol 6020, Austria
Regeneron Research Site
Chicoutimi, Quebec G7H 7K9, Canada
Regeneron Research Site
Québec, Quebec GIV 4W2, Canada
Regeneron Research Site
Praha, 128 08, Czechia
Regeneron Research Site
Marseille, 13285, France
Regeneron Research Site
Paris, 75651, France
Regeneron Research Site
Berlin, 12200, Germany
Regeneron Research Site
Athens, 17674, Greece
Regeneron Research Site
Ioánnina, 45500, Greece
Regeneron Research Site
Napoli, 80131, Italy
Regeneron Research Site
Roma, 00161, Italy
Regeneron Research Site
Nishinomiya, Hyogo 662-0918, Japan
Regeneron Research Site
Kanazawa, Ishikawa 920-8641, Japan
Regeneron Research Site
Suita, Osaka 565-8565, Japan
Regeneron Research Site
Parktown, Johannesburg 2000, South Africa
Regeneron Research Site
Cape Town, Western Cape 7925, South Africa
Regeneron Study Site
Taipei, 11217, Taiwan
Regeneron Research Site
Besevler, Ankara 06500, Turkey
Regeneron Research Site
İzmir, Bornova 35040, Turkey
Regeneron Research Site
Ivano-Frankivs'k, 76005, Ukraine
Regeneron Research Site
Kharkiv, 61039, Ukraine
Regeneron Research Site
Kharkiv, 61176, Ukraine
Regeneron Research Site
Kyiv, 02166, Ukraine
Regeneron Research Site
Kyiv, 03680, Ukraine

References and documents

Publications

Blom DJ, Harada-Shiba M, Rubba P, Gaudet D, Kastelein JJP, Charng MJ, Pordy R, Donahue S, Ali S, Dong Y, Khilla N, Banerjee P, Baccara-Dinet M, Rosenson RS. Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial. J Am Coll Cardiol. 2020 Jul 14;76(2):131-142. doi: 10.1016/j.jacc.2020.05.027. PubMed 32646561 ↗

Study documents

Study protocol · Jan 4, 2019
Statistical analysis plan · Aug 7, 2019

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 29, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03156621
Lead sponsor: Regeneron Pharmaceuticals
Collaborators: Sanofi
Responsible party: Sponsor
First posted: May 17, 2017
Start date: Oct 3, 2017
Primary completion: Sep 27, 2019
Completion: Feb 13, 2020
Results posted: Jun 29, 2021
Last update: Jun 29, 2021

Study contacts

Clinical Trial Management

study director · Regeneron Pharmaceuticals

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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