Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)

NCT01644175 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC11568U1111-1121-4356
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 76

Brief Summary

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9). Primary Objective of the study:

• To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular (CV) risk participants with hypercholesterolemia Secondary Objectives:
• To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
• To evaluate the effect of alirocumab on other lipid parameters
• To evaluate the safety and tolerability of alirocumab

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis

  Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).

  From Baseline to Week 52

Secondary Outcomes (22)

• Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

  From Baseline to Week 52

• Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

  From Baseline to Week 52

• Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

  From Baseline to Week 52

• Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis

  From baseline to Week 52

• Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis

  From Baseline to Week 52

Study Arms (2)

Placebo Q2W

PLACEBO COMPARATOR

Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 52 weeks.

Drug: Placebo (for alirocumab); Drug: Lipid-Modifying Therapy (LMT)

Alirocumab

EXPERIMENTAL

Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.

Drug: Alirocumab; Drug: Lipid-Modifying Therapy (LMT)

Interventions

Placebo (for alirocumab) DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector (also known as pre-filled pen).

Placebo Q2W

Alirocumab DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector (also known as pre-filled pen).

Also known as: SAR236553, REGN727

Alirocumab

Lipid-Modifying Therapy (LMT) DRUG

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

Alirocumab; Placebo Q2W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin with or without other LMT, both at stable dose for at least 4 weeks to 6 weeks prior to screening (Week -2)

You may not qualify if:

• Age \<18 or legal age of adulthood, whichever was greater
• Participants without established CHD or CHD risk equivalent
• LDL-C \<70 mg/dL (\<1.81 mmol/L) and participants with a history of documented cardiovascular disease
• LDL-C \<100 mg/dL (\<2.59 mmol/L) and participants without a history of documented cardiovascular disease
• Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit (Week -2) and from screening to randomization
• Fasting serum triglycerides \> 400 mg/dL (\>4.52 mmol/L)
• The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (76)

Investigational Site Number 840857

Birmingham, Alabama, 35209, United States

Location

Investigational Site Number 840891

Mobile, Alabama, 36693, United States

Location

Investigational Site Number 840876

Montgomery, Alabama, 36109, United States

Location

Investigational Site Number 840865

Glendale, Arizona, 85306, United States

Location

Investigational Site Number 840826

Jonesboro, Arkansas, 72401, United States

Location

Investigational Site Number 840870

Burbank, California, 91505, United States

Location

Investigational Site Number 840851

Los Angeles, California, 90057, United States

Location

Investigational Site Number 840845

Los Gatos, California, 95032, United States

Location

Investigational Site Number 840844

Sacramento, California, 95823, United States

Location

Investigational Site Number 840801

San Jose, California, 95116, United States

Location

Investigational Site Number 840886

Tarzana, California, 91356, United States

Location

Investigational Site Number 840862

Torrance, California, 90505, United States

Location

Investigational Site Number 840893

Vista, California, 92083, United States

Location

Investigational Site Number 840867

Boca Raton, Florida, 33432, United States

Location

Investigational Site Number 840884

Boynton Beach, Florida, 33472, United States

Location

Investigational Site Number 840836

Clearwater, Florida, 33761, United States

Location

Investigational Site Number 840866

Coral Gables, Florida, 33134, United States

Location

Investigational Site Number 840895

Fort Lauderdale, Florida, 33308-4311, United States

Location

Investigational Site Number 840820

Hialeah, Florida, United States

Location

Investigational Site Number 840805

Miami, Florida, 33143, United States

Location

Investigational Site Number 840811

Oviedo, Florida, 32765, United States

Location

Investigational Site Number 840881

Port Orange, Florida, 32127, United States

Location

Investigational Site Number 840816

West Palm Beach, Florida, United States

Location

Investigational Site Number 840850

Columbus, Georgia, 31904, United States

Location

Investigational Site Number 840840

Eagle, Idaho, United States

Location

Investigational Site Number 840842

Chicago, Illinois, 60611, United States

Location

Investigational Site Number 840898

Evanston, Illinois, 60201, United States

Location

Investigational Site Number 840847

Morton, Illinois, 61550, United States

Location

Investigational Site Number 840896

Indianapolis, Indiana, 46260, United States

Location

Investigational Site Number 840894

Michigan City, Indiana, 46360, United States

Location

Investigational Site Number 840838

Mishawaka, Indiana, 46545, United States

Location

Investigational Site Number 840823

Paducah, Kentucky, 42003, United States

Location

Investigational Site Number 840858

Eunice, Louisiana, 70535, United States

Location

Investigational Site Number 840802

New Orleans, Louisiana, 70119, United States

Location

Investigational Site Number 840855

Salisbury, Massachusetts, 01952, United States

Location

Investigational Site Number 840890

Battle Creek, Michigan, 49015, United States

Location

Investigational Site Number 840832

Southfield, Michigan, 48034, United States

Location

Investigational Site Number 840839

Edina, Minnesota, 55435, United States

Location

Investigational Site Number 840888

Minneapolis, Minnesota, 55455, United States

Location

Investigational Site Number 840837

Port Gibson, Mississippi, 39150, United States

Location

Investigational Site Number 840814

Jefferson City, Missouri, 65109, United States

Location

Investigational Site Number 840833

Sparks, Nevada, United States

Location

Investigational Site Number 840817

Newington, New Hampshire, 3801, United States

Location

Investigational Site Number 840853

New Windsor, New York, 12553, United States

Location

Investigational Site Number 840822

Rochester, New York, 14609, United States

Location

Investigational Site Number 840824

Cary, North Carolina, United States

Location

Investigational Site Number 840880

Smithfield, North Carolina, United States

Location

Investigational Site Number 840502

Winston-Salem, North Carolina, 27103, United States

Location

Investigational Site Number 840852

Winston-Salem, North Carolina, 27103, United States

Location

Investigational Site Number 840846

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840899

Cincinnati, Ohio, 45245, United States

Location

Investigational Site Number 840831

Columbus, Ohio, 43231, United States

Location

Investigational Site Number 840860

Kettering, Ohio, 45429, United States

Location

Investigational Site Number 840809

Willoughby Hills, Ohio, 44094, United States

Location

Investigational Site Number 840818

Norman, Oklahoma, 73069, United States

Location

Investigational Site Number 840812

Eugene, Oregon, 97404, United States

Location

Investigational Site Number 840803

Downington, Pennsylvania, 19335, United States

Location

Investigational Site Number 840869

Philadelphia, Pennsylvania, 19146, United States

Location

Investigational Site Number 840825

Pittsburgh, Pennsylvania, 15206, United States

Location

Investigational Site Number 840872

Anderson, South Carolina, 29621, United States

Location

Investigational Site Number 840885

Charleston, South Carolina, 29407, United States

Location

Investigational Site Number 840813

Greer, South Carolina, 29651, United States

Location

Investigational Site Number 840827

Mt. Pleasant, South Carolina, 29464, United States

Location

Investigational Site Number 840868

Corpus Christi, Texas, 78404, United States

Location

Investigational Site Number 840877

Houston, Texas, 77070, United States

Location

Investigational Site Number 840841

Houston, Texas, 77072, United States

Location

Investigational Site Number 840830

San Antonio, Texas, 78224, United States

Location

Investigational Site Number 840854

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 840883

San Antonio, Texas, 78258, United States

Location

Investigational Site Number 840889

Tomball, Texas, 77375, United States

Location

Investigational Site Number 840878

Bountiful, Utah, 84010, United States

Location

Investigational Site Number 840819

Orem, Utah, 84058, United States

Location

Investigational Site Number 840863

Salt Lake City, Utah, 84102, United States

Location

Investigational Site Number 840804

Manassas, Virginia, 20110, United States

Location

Investigational Site Number 840882

Norfolk, Virginia, 23507, United States

Location

Investigational Site Number 840810

Weber City, Virginia, 24290, United States

Location

Related Publications (5)

• Colhoun HM, Robinson JG, Farnier M, Cariou B, Blom D, Kereiakes DJ, Lorenzato C, Pordy R, Chaudhari U. Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC Cardiovasc Disord. 2014 Sep 20;14:121. doi: 10.1186/1471-2261-14-121.

  PMID: 25240705 BACKGROUND

• Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015 Jun;169(6):906-915.e13. doi: 10.1016/j.ahj.2015.03.004. Epub 2015 Mar 13.

  PMID: 26027630 RESULT

• 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.

  PMID: 34298554 DERIVED

• 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.

  PMID: 30183102 DERIVED

• 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.

  PMID: 27777279 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact -US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: July 18, 2012
• Study Start: July 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: November 6, 2015
• Results First Posted: November 6, 2015

Record last verified: 2015-10

Locations

US (76)