Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH)

NCT ID: NCT01617655

Last Updated: 2016-10-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2015-01-31

Brief Summary

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Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).

Primary Objective of the study:

To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.

Secondary Objectives:

* To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
* To evaluate the effects of alirocumab on other lipid parameters
* To evaluate the safety and tolerability of alirocumab

Detailed Description

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The maximum study duration was planned to be 89 weeks per participant including participants who successfully completed the 78-week treatment period had the possibility to join an open-label extension study (LTS13463, NCT01954394) at the end of the treatment period.

Conditions

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Hypercholesterolaemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo Q2W

Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.

Group Type PLACEBO_COMPARATOR

Placebo (for alirocumab)

Intervention Type DRUG

Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).

Lipid Modifying Therapy (LMT)

Intervention Type DRUG

Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.

Alirocumab 150 mg Q2W

Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

Group Type EXPERIMENTAL

Alirocumab

Intervention Type DRUG

Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).

Lipid Modifying Therapy (LMT)

Intervention Type DRUG

Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.

Interventions

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Alirocumab

Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).

Intervention Type DRUG

Placebo (for alirocumab)

Solution for subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre filled pen).

Intervention Type DRUG

Lipid Modifying Therapy (LMT)

Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.

Intervention Type DRUG

Other Intervention Names

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SAR236553 REGN727 Praluent

Eligibility Criteria

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Inclusion Criteria

* Participants with heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy.

Exclusion Criteria

* Age \< 18 years
* LDL-C \< 160 mg/dL (\< 4.14 mmol/L) at the screening visit (Week-3).
* Fasting serum triglycerides \> 400 mg/dL (\> 4.52 mmol/L) during the screening period.
* Known history of homozygous familial hypercholesterolemia.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 840742

Bell Gardens, California, United States

Site Status

Investigational Site Number 840703

Newport Beach, California, United States

Site Status

Investigational Site Number 840712

Newport Beach, California, United States

Site Status

Investigational Site Number 840743

Northridge, California, United States

Site Status

Investigational Site Number 840734

Washington D.C., District of Columbia, United States

Site Status

Investigational Site Number 840738

Miami, Florida, United States

Site Status

Investigational Site Number 840710

Ponte Vedra, Florida, United States

Site Status

Investigational Site Number 840701

New York, New York, United States

Site Status

Investigational Site Number 840702

Durham, North Carolina, United States

Site Status

Investigational Site Number 840714

Cincinnati, Ohio, United States

Site Status

Investigational Site Number 840705

Philadelphia, Pennsylvania, United States

Site Status

Investigational Site Number 840709

Philadelphia, Pennsylvania, United States

Site Status

Investigational Site Number 840713

Philadelphia, Pennsylvania, United States

Site Status

Investigational Site Number 840736

Dallas, Texas, United States

Site Status

Investigational Site Number 124704

Québec, , Canada

Site Status

Investigational Site Number 124703

Sherbrooke, , Canada

Site Status

Investigational Site Number 528713

Amsterdam, , Netherlands

Site Status

Investigational Site Number 528701

Amsterdam, , Netherlands

Site Status

Investigational Site Number 528704

Groningen, , Netherlands

Site Status

Investigational Site Number 528716

Leiden, , Netherlands

Site Status

Investigational Site Number 528709

Utrecht, , Netherlands

Site Status

Investigational Site Number 643706

Arkhangelsk, , Russia

Site Status

Investigational Site Number 643705

Kazan', , Russia

Site Status

Investigational Site Number 643703

Moscow, , Russia

Site Status

Investigational Site Number 643711

Moscow, , Russia

Site Status

Investigational Site Number 643708

Moscow, , Russia

Site Status

Investigational Site Number 643710

Saint Petersburg, , Russia

Site Status

Investigational Site Number 643709

Saint Petersburg, , Russia

Site Status

Investigational Site Number 643702

Saint Petersburg, , Russia

Site Status

Investigational Site Number 643707

Yaroslavl, , Russia

Site Status

Investigational Site Number 710701

Bloemfontein, , South Africa

Site Status

Investigational Site Number 710704

Bloemfontein, , South Africa

Site Status

Investigational Site Number 710706

Cap Town, , South Africa

Site Status

Investigational Site Number 710702

Parktown, , South Africa

Site Status

Investigational Site Number 710703

Somerset West, , South Africa

Site Status

Countries

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United States Canada Netherlands Russia South Africa

References

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Kastelein JJ, Robinson JG, Farnier M, Krempf M, Langslet G, Lorenzato C, Gipe DA, Baccara-Dinet MT. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther. 2014 Jun;28(3):281-9. doi: 10.1007/s10557-014-6523-z.

Reference Type BACKGROUND
PMID: 24842558 (View on PubMed)

Ginsberg HN, Rader DJ, Raal FJ, Guyton JR, Baccara-Dinet MT, Lorenzato C, Pordy R, Stroes E. Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/dl or Higher. Cardiovasc Drugs Ther. 2016 Oct;30(5):473-483. doi: 10.1007/s10557-016-6685-y.

Reference Type RESULT
PMID: 27618825 (View on PubMed)

Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.

Reference Type DERIVED
PMID: 34298554 (View on PubMed)

Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

Reference Type DERIVED
PMID: 30183102 (View on PubMed)

Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4.

Reference Type DERIVED
PMID: 28964736 (View on PubMed)

Kastelein JJ, Hovingh GK, Langslet G, Baccara-Dinet MT, Gipe DA, Chaudhari U, Zhao J, Minini P, Farnier M. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Jan-Feb;11(1):195-203.e4. doi: 10.1016/j.jacl.2016.12.004. Epub 2016 Dec 28.

Reference Type DERIVED
PMID: 28391886 (View on PubMed)

Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.

Reference Type DERIVED
PMID: 27777279 (View on PubMed)

Other Identifiers

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U1111-1128-5459

Identifier Type: OTHER

Identifier Source: secondary_id

2012-001096-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC12732

Identifier Type: -

Identifier Source: org_study_id

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