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

June 7, 2021 updated by: Regeneron Pharmaceuticals

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
69

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Alirocumab SC Q2W
Other Names:
  • SAR236553
  • REGN727
  • PRALUENT®
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
Alirocumab SC Q2W
Other Names:
  • SAR236553
  • REGN727
  • PRALUENT®
Drug: Placebo
Matching placebo SC Q2W

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline to Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline to Week 12
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.
Baseline to Week 12
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.
Baseline to Week 12
Percentage of Participants With ≥15% Reduction in LDL-C at Week 12
Time Frame: At Week 12
ITT estimand
At Week 12
Percentage of Participants With ≥30% Reduction in LDL-C at Week 12
Time Frame: At Week 12
ITT estimand
At Week 12
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.
Baseline to Week 12
Percentage of Participants With ≥50% Reduction in LDL-C at Week 12
Time Frame: At Week 12
ITT estimand
At Week 12
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.
Baseline to Week 12
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.
Baseline to Week 12
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.
Baseline to Week 12
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.
Baseline to Week 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.
Baseline to Week 12
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.
Baseline to Week 12
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.
Baseline to Week 12
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.
Baseline to Week 12
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.
Baseline to Week 12
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.
Baseline to Week 12
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.
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
At Week 12
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
Baseline to Week 12
Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time
Time Frame: 26 weeks
26 weeks
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.
Baseline to week 32 (End of Study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Regeneron Pharmaceuticals

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 3, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 27, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 13, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 15, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 17, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 29, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R727-CL-1628
  • 2017-000351-95 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Homozygous Familial Hypercholesterolemia

Clinical Trials on Alirocumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings