Clinical trial NCT01644474: Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia
Official title: A Randomized, Double-Blind, Active-Controlled, Parallel-Group Study to Evaluate the Efficacy And Safety of SAR236553/REGN727 Over 24 Weeks in Patients With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2012-07-19
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: The maximum study duration was 34 weeks per participant, including a 24-week randomized treatment period.

Eligibility criteria: Inclusion criteria:

* Participants with hypercholesterolemia

Exclusion criteria:

* 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.

Primary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
timeFrame: Up to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Investigational Site Number 840603
state: Kansas
city: Cincinnati
country: United States
facility: Investigational Site Number 840601
state: Ohio
city: Richmond
country: United States
facility: Investigational Site Number 840602
state: Virginia
city: Antwerpen
country: Belgium
facility: Investigational Site Number 056601
city: Helsinki
country: Finland
facility: Investigational Site Number 246601
city: Groningen
country: Netherlands
facility: Investigational Site Number 528602
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528601
city: Velp
country: Netherlands
facility: Investigational Site Number 528603
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.