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

NCT01617655 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC12732U1111-1128-54592012-001096-37
• Study Type: interventional
• Target: 107
• Locations: 5 countries
• Sites: 35

Brief Summary

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

Conditions

Hypercholesterolaemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Calculated LDL-C at Week 24 - 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 (24)

• 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 B (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

Other Outcomes (3)

• Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis

  From Baseline to Week 52

• Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis

  From Baseline to Week 78

• Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis

  From Baseline to Week 78

Study Arms (2)

Placebo Q2W

PLACEBO COMPARATOR

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

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

Alirocumab 150 mg Q2W

EXPERIMENTAL

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

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

Interventions

Alirocumab 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).

Also known as: SAR236553, REGN727, Praluent

Alirocumab 150 mg Q2W

Placebo (for alirocumab) 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).

Placebo Q2W

Lipid Modifying Therapy (LMT) DRUG

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

Alirocumab 150 mg Q2W; 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 heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (35)

Investigational Site Number 840742

Bell Gardens, California, 90201, United States

Location

Investigational Site Number 840703

Newport Beach, California, 92660, United States

Location

Investigational Site Number 840712

Newport Beach, California, 92663, United States

Location

Investigational Site Number 840743

Northridge, California, 91324, United States

Location

Investigational Site Number 840734

Washington D.C., District of Columbia, 20037, United States

Location

Investigational Site Number 840738

Miami, Florida, 33165, United States

Location

Investigational Site Number 840710

Ponte Vedra, Florida, 32081, United States

Location

Investigational Site Number 840701

New York, New York, 10032, United States

Location

Investigational Site Number 840702

Durham, North Carolina, 27710, United States

Location

Investigational Site Number 840714

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840705

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 840709

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 840713

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 840736

Dallas, Texas, 75216, United States

Location

Investigational Site Number 124704

Québec, G1V 4M6, Canada

Location

Investigational Site Number 124703

Sherbrooke, J1H 5N4, Canada

Location

Investigational Site Number 528713

Amsterdam, 1091 AC, Netherlands

Location

Investigational Site Number 528701

Amsterdam, 1105 AZ, Netherlands

Location

Investigational Site Number 528704

Groningen, 9728 NT, Netherlands

Location

Investigational Site Number 528716

Leiden, 2333 ZA, Netherlands

Location

Investigational Site Number 528709

Utrecht, 3582 KE, Netherlands

Location

Investigational Site Number 643706

Arkhangelsk, 163000, Russia

Location

Investigational Site Number 643705

Kazan', 420012, Russia

Location

Investigational Site Number 643703

Moscow, 111539, Russia

Location

Investigational Site Number 643711

Moscow, 121552, Russia

Location

Investigational Site Number 643708

Moscow, 129301, Russia

Location

Investigational Site Number 643710

Saint Petersburg, 193079, Russia

Location

Investigational Site Number 643709

Saint Petersburg, 194291, Russia

Location

Investigational Site Number 643702

Saint Petersburg, 197341, Russia

Location

Investigational Site Number 643707

Yaroslavl, 150062, Russia

Location

Investigational Site Number 710701

Bloemfontein, 9301, South Africa

Location

Investigational Site Number 710704

Bloemfontein, 9301, South Africa

Location

Investigational Site Number 710706

Cap Town, 7530, South Africa

Location

Investigational Site Number 710702

Parktown, 2193, South Africa

Location

Investigational Site Number 710703

Somerset West, 7130, South Africa

Location

Related Publications (7)

• 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.

  PMID: 24842558 BACKGROUND

• 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.

  PMID: 27618825 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

• 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.

  PMID: 28964736 DERIVED

• 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.

  PMID: 28391886 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

Limitations and Caveats

Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report form (eCRF).

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: June 8, 2012
• First Posted: June 12, 2012
• Study Start: June 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: January 1, 2015
• Last Updated: October 4, 2016
• Results First Posted: November 6, 2015

Record last verified: 2016-09

Locations

ZA (5); NL (5); CA (2); US (14); RU (9)