Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

NCT ID: NCT03156621

Last Updated: 2021-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-03
• Study Completion Date: 2020-02-13

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Alirocumab SC Q2W

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

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Alirocumab SC Q2W

Placebo

Intervention Type: DRUG

Matching placebo SC Q2W

Interventions

Alirocumab

Alirocumab SC Q2W

Intervention Type: DRUG

Placebo

Matching placebo SC Q2W

Intervention Type: DRUG

Other Intervention Names

PRALUENT®; REGN727; SAR236553

Eligibility Criteria

Inclusion Criteria

1. 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

2. Receiving a stable dose of a statin at the screening visit (documentation if statin ineffective or patient unable to tolerate statin)

3. 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

Exclusion Criteria

1. Documented evidence of a null mutation in both LDLR alleles

2. Use of a PCSK9 inhibitor within 10 weeks from screening visit

3. 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.

4. 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.

5. 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.

6. 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

7. Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at the screening visit (1 repeat measurement is allowed).

8. LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit

9. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

Regeneron Research Site

Boca Raton, Florida, United States

Regeneron Research Site

New York, New York, United States

Regeneron Research Site

Cincinnati, Ohio, United States

Regeneron Study Site

Dallas, Texas, United States

Regeneron Research Site

Innsbruck, Tyrol, Austria

Regeneron Research Site

Chicoutimi, Quebec, Canada

Regeneron Research Site

Québec, Quebec, Canada

Regeneron Research Site

Prague, , Czechia

Regeneron Research Site

Marseille, , France

Regeneron Research Site

Paris, , France

Regeneron Research Site

Berlin, , Germany

Regeneron Research Site

Athens, , Greece

Regeneron Research Site

Ioannina, , Greece

Regeneron Research Site

Napoli, , Italy

Regeneron Research Site

Roma, , Italy

Regeneron Research Site

Nishinomiya, Hyōgo, Japan

Regeneron Research Site

Kanazawa, Ishikawa-ken, Japan

Regeneron Research Site

Suita, Osaka, Japan

Regeneron Research Site

Parktown, Johannesburg, South Africa

Regeneron Research Site

Cape Town, Western Cape, South Africa

Regeneron Study Site

Taipei, , Taiwan

Regeneron Research Site

Beşevler, Ankara, Turkey (Türkiye)

Regeneron Research Site

Izmir, Bornova, Turkey (Türkiye)

Regeneron Research Site

Ivano-Frankivsk, , Ukraine

Regeneron Research Site

Kharkiv, , Ukraine

Regeneron Research Site

Kharkiv, , Ukraine

Regeneron Research Site

Kyiv, , Ukraine

Regeneron Research Site

Kyiv, , Ukraine

Countries

United States; Austria; Canada; Czechia; France; Germany; Greece; Italy; Japan; South Africa; Taiwan; Turkey (Türkiye); Ukraine

References

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.

Reference Type: DERIVED

PMID: 32646561 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000351-95

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R727-CL-1628

Identifier Type: -

Identifier Source: org_study_id