Clinical trial NCT01709513: Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)
Official title: A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study to Evaluate the Efficacy and Safety of REGN727/SAR236553 in Patients With Primary Hypercholesterolemia Who Are Intolerant to Statins
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2012-10-18
Enrollment: 314
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: This is a randomized, double-blind, double-dummy, active-controlled, parallel-group, multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe in participants with primary hypercholesterolemia and moderate, high, or very high CV risk, who are intolerant to statins. An atorvastatin arm is added to determine that the population selected in the study is a truly statin intolerant population by assessing skeletal muscle-related adverse events.


Eligibility criteria: Inclusion:

1. Patients with primary hypercholesterolemia \[Heterozygous Familial Hypercholesterolemia (heFH) or non-FH\] with moderate, high or very high CV risk and a history of statin intolerance
2. Provide signed informed consent

Exclusion:

1. Calculated serum LDL-C \<70 mg/dL (1.81 mmol/L) and very high CV risk at the screening visit
2. Calculated serum LDL-C \<100 mg/dL (2.59 mmol/L) and high or moderate CV risk at the screening visit
3. A 10-year fatal cardiovascular disease risk score \<1% at the screening visit

(The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this 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 24 - On--Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24 -- On--Treatment 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 Non--HDL-C at Week 24 -- On--Treatment 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 12
measure: Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
timeFrame: Up to Week 24
measure: Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment 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 Fasting Triglycerides at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A-1 at Week 24 - 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 12
measure: Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis
timeFrame: From Baseline to Week 12
Other outcomes:
measure: Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)
timeFrame: From Baseline up to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis
timeFrame: From Baseline up to Week 24
Locations:
city: Anaheim
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Mission Viejo
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Northridge
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Hartford
country: United States
state: Connecticut
city: Boynton Beach
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Lakeland
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Trinity
country: United States
state: Florida
city: Addison
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Kansas City
country: United States
state: Kansas
city: Auburn
country: United States
state: Maine
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Clifton
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Poughkeepsie
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Danville
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Port Matilda
country: United States
state: Pennsylvania
city: Scranton
country: United States
state: Pennsylvania
city: Wilkes-Barre
country: United States
state: Pennsylvania
city: Summerville
country: United States
state: South Carolina
city: Kingsport
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Feldkirch
country: Austria
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Chicoutimi
country: Canada
state: Quebec
city: Montreal (2 locations)
country: Canada
state: Quebec
city: Sainte-Foy
country: Canada
state: Quebec
city: Bron
country: France
city: Dijon
country: France
city: Lille
country: France
city: Paris
country: France
city: Saint-Herblain
country: France
city: Venissieux
country: France
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Ofakim
country: Israel
city: Safed
country: Israel
city: Tel-Hashomer
country: Israel
city: Cinisello Balsamo
country: Italy
city: Napoli
country: Italy
city: Palermo
country: Italy
city: Roma
country: Italy
city: Oslo (2 Locations)
country: Norway
city: Burton-on-Trent
country: United Kingdom
city: Chesterfield
country: United Kingdom
city: Isle Of White
country: United Kingdom
city: Londonderry/N. Ireland
country: United Kingdom
city: Peterborough
country: United Kingdom
city: Salford
country: United Kingdom
city: Stevenage
country: United Kingdom
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol. 2014 Nov-Dec;8(6):554-561. doi: 10.1016/j.jacl.2014.09.007. Epub 2014 Sep 19.
citation: Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, Bruckert E, Jacobson TA, Kopecky SL, Baccara-Dinet MT, Du Y, Pordy R, Gipe DA; ODYSSEY ALTERNATIVE Investigators. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol. 2015 Nov-Dec;9(6):758-769. doi: 10.1016/j.jacl.2015.08.006. Epub 2015 Aug 29.
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: Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, Bruckert E, Jacobson TA, Baccara-Dinet MT, Zhao J, Donahue S, Ali S, Manvelian G, Pordy R. Efficacy and safety of alirocumab in statin-intolerant patients over 3 years: open-label treatment period of the ODYSSEY ALTERNATIVE trial. J Clin Lipidol. 2020 Jan-Feb;14(1):88-97.e2. doi: 10.1016/j.jacl.2020.01.001. Epub 2020 Jan 13.
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: 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.
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.