Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

NCT03156621 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: R727-CL-16282017-000351-95
• Study Type: interventional
• Target: 69
• Locations: 13 countries
• Sites: 28

Brief 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

Homozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 12

Secondary Outcomes (22)

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

  Baseline to Week 12

• Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12

  Baseline to Week 12

• Percent Change in Total Cholesterol (TC) From Baseline to Week 12

  Baseline to Week 12

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

  At Week 12

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

  At Week 12

Study Arms (2)

Alirocumab SC Q2W

EXPERIMENTAL

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

Placebo SC Q2W

EXPERIMENTAL

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

Alirocumab DRUG

Alirocumab SC Q2W

Also known as: PRALUENT®, REGN727, SAR236553

Alirocumab SC Q2W; Placebo SC Q2W

Placebo DRUG

Matching placebo SC Q2W

Placebo SC Q2W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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):
• Documented homozygous or compound heterozygous mutations in both low-density lipoprotein receptor (LDLR) alleles
• Presence of homozygous or compound heterozygous mutations in Apo B, PCSK9 or LDL receptor adaptor protein 1 (LDLRAP1)
• Presence of double heterozygous mutations, i.e, mutations on different genes in the LDLR, Apo B or PCSK9 alleles
• 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
• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (28)

Regeneron Research Site

Boca Raton, Florida, 33434, United States

Location

Regeneron Research Site

New York, New York, 10029, United States

Location

Regeneron Research Site

Cincinnati, Ohio, 45227, United States

Location

Regeneron Study Site

Dallas, Texas, 78226, United States

Location

Regeneron Research Site

Innsbruck, Tyrol, 6020, Austria

Location

Regeneron Research Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Regeneron Research Site

Québec, Quebec, GIV 4W2, Canada

Location

Regeneron Research Site

Prague, 128 08, Czechia

Location

Regeneron Research Site

Marseille, 13285, France

Location

Regeneron Research Site

Paris, 75651, France

Location

Regeneron Research Site

Berlin, 12200, Germany

Location

Regeneron Research Site

Athens, 17674, Greece

Location

Regeneron Research Site

Ioannina, 45500, Greece

Location

Regeneron Research Site

Napoli, 80131, Italy

Location

Regeneron Research Site

Roma, 00161, Italy

Location

Regeneron Research Site

Nishinomiya, Hyōgo, 662-0918, Japan

Location

Regeneron Research Site

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Regeneron Research Site

Suita, Osaka, 565-8565, Japan

Location

Regeneron Research Site

Parktown, Johannesburg, 2000, South Africa

Location

Regeneron Research Site

Cape Town, Western Cape, 7925, South Africa

Location

Regeneron Study Site

Taipei, 11217, Taiwan

Location

Regeneron Research Site

Beşevler, Ankara, 06500, Turkey (Türkiye)

Location

Regeneron Research Site

Izmir, Bornova, 35040, Turkey (Türkiye)

Location

Regeneron Research Site

Ivano-Frankivsk, 76005, Ukraine

Location

Regeneron Research Site

Kharkiv, 61039, Ukraine

Location

Regeneron Research Site

Kharkiv, 61176, Ukraine

Location

Regeneron Research Site

Kyiv, 02166, Ukraine

Location

Regeneron Research Site

Kyiv, 03680, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 32646561 DERIVED

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844 734 6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 17, 2017
• Study Start: October 3, 2017
• Primary Completion: September 27, 2019
• Study Completion: February 13, 2020
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-06

Locations

IT (2); AU (1); TW (1); UA (5); CA (2); DE (1); GR (2); TU (2); JP (3); CZ (1); US (4); FR (2); ZA (2)