Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)

NCT ID: NCT01709513

Last Updated: 2020-06-23

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

314 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2017-05-31

Brief Summary

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This is a randomized, double-blind, double-dummy, active-controlled, parallel-group, multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe in participants with primary hypercholesterolemia and moderate, high, or very high CV risk, who are intolerant to statins. An atorvastatin arm is added to determine that the population selected in the study is a truly statin intolerant population by assessing skeletal muscle-related adverse events.

Detailed Description

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Conditions

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Hypercholesterolemia

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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Atorvastatin (statin rechallenge arm)

Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable lipid-modifying therapy (LMT).

Group Type OTHER

Atorvastatin

Intervention Type DRUG

Atorvastatin over-encapsulated tablets.

Placebo

Intervention Type DRUG

Placebo for alirocumab, ezitimibe and atorvastatin.

Ezetimibe

Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.

Group Type ACTIVE_COMPARATOR

Ezetimibe

Intervention Type DRUG

Ezetimibe over-encapsulated tablet.

Placebo

Intervention Type DRUG

Placebo for alirocumab, ezitimibe and atorvastatin.

Alirocumab 75 mg/ up to 150 mg

Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.

Group Type EXPERIMENTAL

Alirocumab

Intervention Type DRUG

Alirocumab SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Placebo

Intervention Type DRUG

Placebo for alirocumab, ezitimibe and atorvastatin.

Interventions

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Atorvastatin

Atorvastatin over-encapsulated tablets.

Intervention Type DRUG

Ezetimibe

Ezetimibe over-encapsulated tablet.

Intervention Type DRUG

Alirocumab

Alirocumab SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Intervention Type DRUG

Placebo

Placebo for alirocumab, ezitimibe and atorvastatin.

Intervention Type DRUG

Other Intervention Names

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Zetia REGN727/SAR236553

Eligibility Criteria

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Inclusion Criteria

1. Patients with primary hypercholesterolemia \[Heterozygous Familial Hypercholesterolemia (heFH) or non-FH\] with moderate, high or very high CV risk and a history of statin intolerance
2. Provide signed informed consent

Exclusion:

1. Calculated serum LDL-C \<70 mg/dL (1.81 mmol/L) and very high CV risk at the screening visit
2. Calculated serum LDL-C \<100 mg/dL (2.59 mmol/L) and high or moderate CV risk at the screening visit
3. A 10-year fatal cardiovascular disease risk score \<1% at the screening visit
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Anaheim, California, United States

Site Status

Beverly Hills, California, United States

Site Status

Mission Viejo, California, United States

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Newport Beach, California, United States

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Northridge, California, United States

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Thousand Oaks, California, United States

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Hartford, Connecticut, United States

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Boynton Beach, Florida, United States

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Jacksonville, Florida, United States

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Lakeland, Florida, United States

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Pembroke Pines, Florida, United States

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Sarasota, Florida, United States

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Tampa, Florida, United States

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Trinity, Florida, United States

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Addison, Illinois, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Kansas City, Kansas, United States

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Auburn, Maine, United States

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Boston, Massachusetts, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Clifton, New Jersey, United States

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New York, New York, United States

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Poughkeepsie, New York, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Marion, Ohio, United States

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Danville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Port Matilda, Pennsylvania, United States

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Scranton, Pennsylvania, United States

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Wilkes-Barre, Pennsylvania, United States

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Summerville, South Carolina, United States

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Kingsport, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Salt Lake City, Utah, United States

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Richmond, Virginia, United States

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Feldkirch, , Austria

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Graz, , Austria

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Innsbruck, , Austria

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Chicoutimi, Quebec, Canada

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Montreal (2 Locations), Quebec, Canada

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Sainte-Foy, Quebec, Canada

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Bron, , France

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Dijon, , France

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Lille, , France

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Paris, , France

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Saint-Herblain, , France

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Vénissieux, , France

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Holon, , Israel

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Jerusalem, , Israel

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Ofakim, , Israel

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Safed, , Israel

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Tel Litwinsky, , Israel

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Cinisello Balsamo, , Italy

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Napoli, , Italy

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Palermo, , Italy

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Roma, , Italy

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Oslo (2 Locations), , Norway

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Burton-on-Trent, , United Kingdom

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Chesterfield, , United Kingdom

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Isle of White, , United Kingdom

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Londonderry/N. Ireland, , United Kingdom

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Peterborough, , United Kingdom

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Salford, , United Kingdom

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Stevenage, , United Kingdom

Site Status

Countries

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United States Austria Canada France Israel Italy Norway United Kingdom

References

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Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol. 2014 Nov-Dec;8(6):554-561. doi: 10.1016/j.jacl.2014.09.007. Epub 2014 Sep 19.

Reference Type BACKGROUND
PMID: 25499937 (View on PubMed)

Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, Bruckert E, Jacobson TA, Kopecky SL, Baccara-Dinet MT, Du Y, Pordy R, Gipe DA; ODYSSEY ALTERNATIVE Investigators. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol. 2015 Nov-Dec;9(6):758-769. doi: 10.1016/j.jacl.2015.08.006. Epub 2015 Aug 29.

Reference Type RESULT
PMID: 26687696 (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)

Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, Bruckert E, Jacobson TA, Baccara-Dinet MT, Zhao J, Donahue S, Ali S, Manvelian G, Pordy R. Efficacy and safety of alirocumab in statin-intolerant patients over 3 years: open-label treatment period of the ODYSSEY ALTERNATIVE trial. J Clin Lipidol. 2020 Jan-Feb;14(1):88-97.e2. doi: 10.1016/j.jacl.2020.01.001. Epub 2020 Jan 13.

Reference Type DERIVED
PMID: 32192644 (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)

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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R727-CL-1119

Identifier Type: -

Identifier Source: org_study_id

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