Clinical trial NCT01926782: Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1)
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab in Patients With Primary Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2013-08-21
Enrollment: 803
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study was conducted in 2 separate populations concurrently: subjects receiving concomitant statin therapy and subjects not receiving concomitant statin therapy. Subjects receiving concomitant statin were to receive stable daily doses of rosuvastatin, atorvastatin, or simvastatin for at least 4 weeks. Background treatment with other lipid-modifying therapy (LMT) was allowed for all patients, provided they had been on a stable dose for at least 4 weeks (6 weeks for fenofibrate) prior to study entry.
Primary purpose: TREATMENT

Brief summary: To determine the efficacy, long-term safety, and tolerability of alirocumab 300 mg every 4 weeks (Q4W), in comparison with placebo, as well as its potential as a starting regimen. The dose regimen of 75 mg every 2 weeks (Q2W), as used in other studies, was added as a calibrator.


Eligibility criteria: Inclusion Criteria:

1. Men and women \> age 18 or legal age of majority with elevated LDL-C
2. Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD risk
3. Willing and able to comply with clinic visits and study-related procedures
4. Provided signed informed consent

Exclusion Criteria:

1. Recent (within 3 months prior to the screening visit) myocardial infarction, unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
2. Known history of positive test for human immunodeficiency virus (HIV)
3. Any clinically significant abnormality identified at the time of screening that in the judgment of the investigator or any sub-investigator would preclude safe completion of the study or constrain assessment of endpoints, such as major systemic diseases or participants with short life expectancy.
4. Participants considered by the investigator or any sub-investigator to be inappropriate for this study (e.g, geographic or social), actual or anticipated, that the investigator felt would restrict or limit the participant's participation for the duration of the study.
5. Certain laboratory findings obtained during the screening period

The information listed above is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial and not all inclusion/ exclusion criteria are listed.

Primary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C in Participants Receiving Concomitant Statin Therapy - 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 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - On-treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - On-treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24 in Participants Receiving Concomitant Statin Therapy - 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 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total-C at Week 24 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apo B at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Non-HDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Total-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Total-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percentage of Very High CV Risk Participants Reaching Calculated LDL-C<70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C<100 mg/dL (Without Concomitant Statin Therapy) at Week 24 - ITT Analysis
timeFrame: Up to Week 24
measure: Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (With Concomitant Statin Therapy) 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) (Without Concomitant Statin Therapy) at Week 24 - On-Treatment 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) (With Concomitant Statin Therapy) at Week 24 - On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants (Without Concomitant Statin Therapy) 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 (With Concomitant Statin Therapy) 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 (Without Concomitant Statin Therapy) Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants (With Concomitant Statin Therapy) 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) in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Lipoprotein (a) in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in HDL-C in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Fasting Triglycerides in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A1 in Participants Not Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apo A1 in Participants Receiving Concomitant Statin Therapy at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
Other outcomes:
Locations:
city: Chandler
country: United States
state: Arizona
city: Goodyear
country: United States
state: Arizona
city: Carmichael
country: United States
state: California
city: Fresno
country: United States
state: California
city: West Hills
country: United States
state: California
city: Wildomar
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Golden
country: United States
state: Colorado
city: Boynton Beach
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Safety Harbor
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Gurnee
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Monroe
country: United States
state: Louisiana
city: Auburn
country: United States
state: Maine
city: Methuen
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: St. Louis
country: United States
state: Missouri
city: Rochester
country: United States
state: New York
city: Farmville
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Wilson
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Knoxville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Orem
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: South Jordan
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Kenosha
country: United States
state: Wisconsin
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Victoria
country: Canada
state: British Columbia
city: Oshawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Woodstock
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Trois-Rivieres
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Budapest
country: Hungary
state: Becsi ut
city: Debrecen
country: Hungary
state: HBM
city: Nyiregyhaza
country: Hungary
state: Sz-sz-b_m
city: Ajka
country: Hungary
state: VeszprÃ©m
city: Nagykanizsa
country: Hungary
state: Zala
city: Zalaegerszeg
country: Hungary
state: Zala
city: Tel Hashomer
country: Israel
state: IL
city: Safed
country: Israel
state: ISR
city: Ofakim
country: Israel
state: South
city: Holon
country: Israel
city: Tel Hashomer
country: Israel
city: Skedsmokorset
country: Norway
state: Akershus
city: Oslo
country: Norway
city: Svidnik
country: Slovakia
state: Presov
city: Bratislava
country: Slovakia
state: SK
city: Bratislava
country: Slovakia
state: SR
city: Lucenec
country: Slovakia
city: PovaÅ¾skÃ¡ Bystrica
country: Slovakia
city: Worton Grange, Reading
country: United Kingdom
state: Berkshire
city: Edgbaston
country: United Kingdom
state: Birmingham
city: Llanishen
country: United Kingdom
state: Cardiff
city: Choley
country: United Kingdom
state: Lancashire
city: Waterloo
country: United Kingdom
state: Liverpool
city: Lloyd Street North
country: United Kingdom
state: Manchester
city: Glasgow
country: United Kingdom
state: Scotland
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Roth EM, Kastelein JJP, Cannon CP, Farnier M, McKenney JM, DiCioccio AT, Brunet A, Manvelian G, Sasiela WJ, Baccara-Dinet MT, Zhao J, Robinson JG. Pharmacodynamic relationship between PCSK9, alirocumab, and LDL-C lowering in the ODYSSEY CHOICE I trial. J Clin Lipidol. 2020 Sep-Oct;14(5):707-719. doi: 10.1016/j.jacl.2020.07.009. Epub 2020 Jul 25.
citation: Muller-Wieland D, Rader DJ, Moriarty PM, Bergeron J, Langslet G, Ray KK, Manvelian G, Thompson D, Bujas-Bobanovic M, Roth EM. Efficacy and Safety of Alirocumab 300 mg Every 4 Weeks in Individuals With Type 2 Diabetes on Maximally Tolerated Statin. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5253-5262. doi: 10.1210/jc.2018-02703.
citation: Roth EM, Moriarty PM, Bergeron J, Langslet G, Manvelian G, Zhao J, Baccara-Dinet MT, Rader DJ; ODYSSEY CHOICE I investigators. A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis. 2016 Nov;254:254-262. doi: 10.1016/j.atherosclerosis.2016.08.043. Epub 2016 Aug 31.