Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

NCT01623115 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC12492U1111-1121-42752011-005109-56
• Study Type: interventional
• Target: 486
• Locations: 14 countries
• Sites: 91

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

Hypercholesterolemia

Keywords

PCSK9

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 (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

PLACEBO COMPARATOR

Placebo for alirocumab every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.

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

Alirocumab 75 mg/Up to 150 mg Q2W

EXPERIMENTAL

Alirocumab 75 mg Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥ 70 mg/dL (1.81 mmol/L) at Week 8.

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 75 mg/Up to 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

Lipid Modifying Therapy (LMT) DRUG

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

Alirocumab 75 mg/Up to 150 mg Q2W; Placebo

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 or legal age of adulthood, whichever is greater
• LDL-C \< 70 mg/dL (1.81 mmol/L) and with cardiovascular disease
• LDL-C \< 100 mg/dL (2.59 mmol/L) and without cardiovascular disease
• Fasting serum triglycerides \> 400 mg/dL (4.52 mmol/L)
• 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 (91)

Investigational Site Number 840417

Bell Gardens, California, 90201, United States

Location

Investigational Site Number 840429

Long Beach, California, 90801, United States

Location

Investigational Site Number 840419

Los Angeles, California, 90048, United States

Location

Investigational Site Number 840421

Mission Viejo, California, 92691, United States

Location

Investigational Site Number 840412

Newport Beach, California, 92660, United States

Location

Investigational Site Number 840428

Newport Beach, California, United States

Location

Investigational Site Number 840461

Northridge, California, 91324, United States

Location

Investigational Site Number 840452

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

Location

Investigational Site Number 840456

Miami, Florida, 33165, United States

Location

Investigational Site Number 840418

Ponte Vedra, Florida, 32081, United States

Location

Investigational Site Number 840455

Evanston, Illinois, 60201, United States

Location

Investigational Site Number 840415

Kansas City, Kansas, 66160-7321, United States

Location

Investigational Site Number 840425

Auburn, Maine, 04210, United States

Location

Investigational Site Number 840411

Boston, Massachusetts, 02114, United States

Location

Investigational Site Number 840409

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840407

Morristown, New Jersey, 07962, United States

Location

Investigational Site Number 840408

New York, New York, 10032, United States

Location

Investigational Site Number 840401

Charlotte, North Carolina, 28207, United States

Location

Investigational Site Number 840410

Durham, North Carolina, 27710, United States

Location

Investigational Site Number 840430

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840424

Portland, Oregon, 97201-3098, United States

Location

Investigational Site Number 840404

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 840426

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 840406

Nashville, Tennessee, 37232, United States

Location

Investigational Site Number 840460

Dallas, Texas, 75216, United States

Location

Investigational Site Number 840422

Bountiful, Utah, 84010, United States

Location

Investigational Site Number 040403

Graz, 8036, Austria

Location

Investigational Site Number 040402

Vienna, 1130, Austria

Location

Investigational Site Number 040405

Vienna, Austria

Location

Investigational Site Number 124404

Chicoutimi, G7H 5H6, Canada

Location

Investigational Site Number 124401

Montreal, H2W 1R7, Canada

Location

Investigational Site Number 124403

Québec, G1V 4M6, Canada

Location

Investigational Site Number 124406

Sherbrooke, J1H 5N4, Canada

Location

Investigational Site Number 124407

Toronto, M5C 2T2, Canada

Location

Investigational Site Number 203401

Prague, 140 00, Czechia

Location

Investigational Site Number 203403

Prague, 180 00, Czechia

Location

Investigational Site Number 203405

Uherské Hradiště, Czechia

Location

Investigational Site Number 203402

Zlín, 760 00, Czechia

Location

Investigational Site Number 208401

Copenhagen, Denmark

Location

Investigational Site Number 208403

Esbjerg, 6700, Denmark

Location

Investigational Site Number 250403

Dijon, 21000, France

Location

Investigational Site Number 250401

Paris, 75651, France

Location

Investigational Site Number 250402

Saint-Herblain, 44093, France

Location

Investigational Site Number 376402

Holon, 76100, Israel

Location

Investigational Site Number 376405

Jerusalem, Israel

Location

Investigational Site Number 376404

Safed, 13100, Israel

Location

Investigational Site Number 376401

Tel Litwinsky, 52621, Israel

Location

Investigational Site Number 528406

Amsterdam, 1105 AZ, Netherlands

Location

Investigational Site Number 528410

Amsterdam, Netherlands

Location

Investigational Site Number 528408

Den Helder, 1782 GZ, Netherlands

Location

Investigational Site Number 528402

Groningen, 9728 NT, Netherlands

Location

Investigational Site Number 528411

Leiden, 2333 ZA, Netherlands

Location

Investigational Site Number 528416

Maastricht, 6229 HX, Netherlands

Location

Investigational Site Number 528409

Nieuwegein, 3435 CM, Netherlands

Location

Investigational Site Number 528412

Sliedrecht, Netherlands

Location

Investigational Site Number 578401

Bodø, 8092, Norway

Location

Investigational Site Number 643402

Arkhangelsk, 163000, Russia

Location

Investigational Site Number 643407

Kazan', 420012, Russia

Location

Investigational Site Number 643409

Moscow, 111539, Russia

Location

Investigational Site Number 643413

Moscow, 121552, Russia

Location

Investigational Site Number 643401

Moscow, 129301, Russia

Location

Investigational Site Number 643412

Novisibirsk, Russia

Location

Investigational Site Number 643408

Saint Petersburg, 193079, Russia

Location

Investigational Site Number 643406

Saint Petersburg, 194291, Russia

Location

Investigational Site Number 643404

Saint Petersburg, 197341, Russia

Location

Investigational Site Number 643410

Yaroslavl, 150062, Russia

Location

Investigational Site Number 710401

Bloemfontein, South Africa

Location

Investigational Site Number 710405

Bloemfontein, South Africa

Location

Investigational Site Number 710406

Cap Town, 7530, South Africa

Location

Investigational Site Number 710402

Cape Town, 7708, South Africa

Location

Investigational Site Number 710407

Parktown, 2193, South Africa

Location

Investigational Site Number 710403

Parow, 7500, South Africa

Location

Investigational Site Number 710408

Pretoria, South Africa

Location

Investigational Site Number 710404

Rondebosch, South Africa

Location

Investigational Site Number 710409

Somerset West, 7130, South Africa

Location

Investigational Site Number 724403

A Coruña, 15006, Spain

Location

Investigational Site Number 724408

Barcelona, 08036, Spain

Location

Investigational Site Number 724406

Córdoba, 14004, Spain

Location

Investigational Site Number 724407

L'Hospitalet de Llobregat, 08907, Spain

Location

Investigational Site Number 724409

Madrid, 28029, Spain

Location

Investigational Site Number 724401

Madrid, 28040, Spain

Location

Investigational Site Number 724405

Madrid, 28040, Spain

Location

Investigational Site Number 724404

Reus, 43201, Spain

Location

Investigational Site Number 724402

Zaragoza, 50009, Spain

Location

Investigational Site Number 752404

Gothenburg, 41345, Sweden

Location

Investigational Site Number 752401

Stockholm, 111 35, Sweden

Location

Investigational Site Number 826402

London, United Kingdom

Location

Investigational Site Number 826403

London, United Kingdom

Location

Investigational Site Number 826408

London, United Kingdom

Location

Investigational Site Number 826409

London, United Kingdom

Location

Investigational Site Number 826405

Manchester, M23 9LT, United Kingdom

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

• Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, Zhao J, Pordy R, Baccara-Dinet MT, Gipe DA, Geiger MJ, Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015 Nov 14;36(43):2996-3003. doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.

  PMID: 26330422 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 15, 2012
• First Posted: June 19, 2012
• Study Start: July 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 8, 2016
• Results First Posted: November 4, 2015

Record last verified: 2016-01

Locations

SE (2); CZ (4); AU (3); CA (5); DK (2); IL (4); NL (8); US (26); FR (3); NO (1); RU (10); ES (9); GB (5); ZA (9)