Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (ODYSSEY HoFH)

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Homozygous Familial Hypercholesterolemia

Treatments: Drug: Placebo; Drug: Alirocumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03156621

R727-CL-1628

2017-000351-95 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 69 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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69 participants in 2 patient groups

Alirocumab SC Q2W

Experimental group

Description:

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

Treatment:

Drug: Alirocumab

Placebo SC Q2W

Experimental group

Description:

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

Treatment:

Drug: Alirocumab

Drug: Placebo