Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia

NCT01644474 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC11716U1111-1124-11672011-001424-38
• Study Type: interventional
• Target: 103
• Locations: 4 countries
• Sites: 8

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 demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia. Secondary Objectives:

• To evaluate the effect of alirocumab in comparison with ezetimibe 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 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

  From Baseline to Week 24

Secondary Outcomes (17)

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

  From Baseline to Week 24

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

  From Baseline to Week 24

• Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Apo B at Week 12 - ITT Analysis

  From Baseline to Week 24

Study Arms (2)

Ezetimibe 10 mg

ACTIVE COMPARATOR

Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks.

Drug: Ezetimibe; Drug: Placebo (for Alirocumab)

Alirocumab 75/Up to 150 mg Q2W

EXPERIMENTAL

SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 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: Placebo (for Ezetimibe)

Interventions

Alirocumab DRUG

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using the autoinjector.

Also known as: SAR236553, REGN727

Alirocumab 75/Up to 150 mg Q2W

Ezetimibe DRUG

One over-encapsulated tablet orally once daily at approximately the same time of the day with or without food.

Ezetimibe 10 mg

Placebo (for Alirocumab) DRUG

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self--injection or by another designated person using the autoinjector.

Ezetimibe 10 mg

Placebo (for Ezetimibe) DRUG

One capsule orally once daily at approximately the same time of the day with or without food..

Alirocumab 75/Up to 150 mg 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

You may not qualify if:

• Age \< 18 or legal age of adulthood, whichever was greater
• LDL-C \< 100 mg/dL (\< 2.59 mmol/L) or \> 190 mg/dL (\> 4.9 mmol/L)
• Fasting serum triglycerides (TG) \> 400 mg/dL (\> 4.52 mmol/L)
• Known history of homozygous or heterozygous familial hypercholesterolemia
• The above information was 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 (8)

Investigational Site Number 840603

Overland Park, Kansas, 66212, United States

Location

Investigational Site Number 840601

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840602

Richmond, Virginia, 23227, United States

Location

Investigational Site Number 056601

Antwerp, 2060, Belgium

Location

Investigational Site Number 246601

Helsinki, 00290, Finland

Location

Investigational Site Number 528602

Groningen, 9711 SG, Netherlands

Location

Investigational Site Number 528601

Rotterdam, 3021 HC, Netherlands

Location

Investigational Site Number 528603

Velp, 6883 ES, Netherlands

Location

Related Publications (5)

• Roth EM, Taskinen MR, Ginsberg HN, Kastelein JJ, Colhoun HM, Robinson JG, Merlet L, Pordy R, Baccara-Dinet MT. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int J Cardiol. 2014 Sep;176(1):55-61. doi: 10.1016/j.ijcard.2014.06.049. Epub 2014 Jul 2.

  PMID: 25037695 RESULT

• Roth EM, McKenney JM. ODYSSEY MONO: effect of alirocumab 75 mg subcutaneously every 2 weeks as monotherapy versus ezetimibe over 24 weeks. Future Cardiol. 2015;11(1):27-37. doi: 10.2217/fca.14.82.

  PMID: 25606700 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; Ezetimibe

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to administrative error in the automated process (which was detected after database lock), planned dose up-titration criteria for LDL-C levels was changed from ≥100 mg/dL to ≥70 mg/dL.

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 17, 2012
• First Posted: July 19, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: November 6, 2015
• Results First Posted: November 6, 2015

Record last verified: 2015-10

Locations

US (3); BE (1); NL (3); FI (1)