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Completed

NCT Number: NCT03156621

Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

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

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Regeneron Research Site, Innsbruck, Tyrol, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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):
  • 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

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.

Treatment and study plan

Alirocumab

Drug

Alirocumab SC Q2W

Other names: PRALUENT®, REGN727, SAR236553

Placebo

Drug

Matching placebo SC Q2W

Primary outcomes

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

    Time frame: Baseline to Week 12

    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.

Secondary outcomes

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: At Week 12

    ITT estimand

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

    Time frame: At Week 12

    ITT estimand

  6. Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12

    Time frame: 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.

  7. Percentage of Participants With ≥50% Reduction in LDL-C at Week 12

    Time frame: At Week 12

    ITT estimand

  8. Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis

    Time frame: 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.

  9. Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12

    Time frame: 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.

  10. Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis

    Time frame: 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.

  11. Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

  14. Percent Change in TC From Baseline to Week 12 (On-treatment Estimand)

    Time frame: 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.

  15. Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)

    Time frame: 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.

  16. Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)

    Time frame: 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.

  17. Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)

    Time frame: 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.

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

    Time frame: 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.

  19. 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

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

    Time frame: Baseline to Week 12

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

  21. Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time

    Time frame: 26 weeks

  22. Number of Participants With Adverse Events (AEs)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Collaborators

  • Sanofi

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Alirocumab in Patients With Homozygous Familial Hypercholesterolemia

Acronym: ODYSSEY HoFH

Important dates

Study start
2017
Primary completion
2019
Study completion
2020
First posted
May 17, 2017
Registry last updated
Jun 29, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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