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)

NCT01926782 | Completed Phase 3 Results DMC

• 1 other identifier: R727-CL-1308
• Study Type: interventional
• Target: 803
• Locations: 8 countries
• Sites: 83

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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis

  Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

  From Baseline to Week 24

• Percent Change From Baseline in Calculated LDL-C in Participants Receiving Concomitant Statin Therapy - Intent-to-Treat (ITT Analysis)

  Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model 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 this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.

  From Baseline to Week 24

Secondary Outcomes (46)

• Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Not Receiving Concomitant Statin Therapy - On-Treatment Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Calculated LDL-C at Week 24 in Participants Receiving Concomitant Statin Therapy - On-Treatment Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis

  From Baseline to Week 12

• Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Receiving Concomitant Statin Therapy - ITT Analysis

  From Baseline to Week 12

• Percent Change From Baseline in Calculated LDL-C at Week 12 in Participants Not Receiving Concomitant Statin Therapy - On-treatment Analysis

  From Baseline to Week 12

Study Arms (3)

Placebo Q2W

PLACEBO COMPARATOR

Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks.

Drug: Placebo (for alirocumab); Drug: Statin

Alirocumab 75 mg/ Up 150 mg Q2W

EXPERIMENTAL

One SC injection of each Alirocumab 75 mg and placebo Q2W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.

Drug: Placebo (for alirocumab); Drug: Alirocumab; Drug: Statin

Alirocumab 300 mg/ Up 150 mg Q4W

EXPERIMENTAL

Two SC injections of Alirocumab 150 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8.

Drug: Placebo (for alirocumab); Drug: Alirocumab; Drug: Statin

Interventions

Placebo (for alirocumab) DRUG

Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Alirocumab 300 mg/ Up 150 mg Q4W; Alirocumab 75 mg/ Up 150 mg Q2W; Placebo Q2W

Alirocumab DRUG

Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.

Also known as: SAR236553, REGN727, Praluent

Alirocumab 300 mg/ Up 150 mg Q4W; Alirocumab 75 mg/ Up 150 mg Q2W

Statin DRUG

Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy

Alirocumab 300 mg/ Up 150 mg Q4W; Alirocumab 75 mg/ Up 150 mg Q2W; Placebo Q2W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• Known history of positive test for human immunodeficiency virus (HIV)
• 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.
• 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.
• Certain laboratory findings obtained during the screening period

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (83)

Unknown Facility

Chandler, Arizona, United States

Location

Unknown Facility

Goodyear, Arizona, United States

Location

Unknown Facility

Carmichael, California, United States

Location

Unknown Facility

Fresno, California, United States

Location

Unknown Facility

West Hills, California, United States

Location

Unknown Facility

Wildomar, California, United States

Location

Unknown Facility

Colorado Springs, Colorado, United States

Location

Unknown Facility

Golden, Colorado, United States

Location

Unknown Facility

Boynton Beach, Florida, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Safety Harbor, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Boise, Idaho, United States

Location

Unknown Facility

Meridian, Idaho, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Gurnee, Illinois, United States

Location

Unknown Facility

Evansville, Indiana, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Iowa City, Iowa, United States

Location

Unknown Facility

Kansas City, Kansas, United States

Location

Unknown Facility

Louisville, Kentucky, United States

Location

Unknown Facility

Monroe, Louisiana, United States

Location

Unknown Facility

Auburn, Maine, United States

Location

Unknown Facility

Methuen, Massachusetts, United States

Location

Unknown Facility

Minneapolis, Minnesota, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Rochester, New York, United States

Location

Unknown Facility

Farmville, North Carolina, United States

Location

Unknown Facility

Greensboro, North Carolina, United States

Location

Unknown Facility

Greenville, North Carolina, United States

Location

Unknown Facility

Raleigh, North Carolina, United States

Location

Unknown Facility

Wilson, North Carolina, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Marion, Ohio, United States

Location

Unknown Facility

Tulsa, Oklahoma, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Wyomissing, Pennsylvania, United States

Location

Unknown Facility

Knoxville, Tennessee, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Orem, Utah, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

South Jordan, Utah, United States

Location

Unknown Facility

Norfolk, Virginia, United States

Location

Unknown Facility

Richmond, Virginia, United States

Location

Unknown Facility

Spokane, Washington, United States

Location

Unknown Facility

Tacoma, Washington, United States

Location

Unknown Facility

Kenosha, Wisconsin, United States

Location

Unknown Facility

Varna, Varna, Bulgaria

Location

Unknown Facility

Sofia, Bulgaria

Location

Unknown Facility

Victoria, British Columbia, Canada

Location

Unknown Facility

Oshawa, Ontario, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

Woodstock, Ontario, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Unknown Facility

Québec, Quebec, Canada

Location

Unknown Facility

Trois-Rivières, Quebec, Canada

Location

Unknown Facility

Budapest, Becsi Ut, Hungary

Location

Unknown Facility

Debrecen, HBM, Hungary

Location

Unknown Facility

Nyíregyháza, Sz-sz-b_m, Hungary

Location

Unknown Facility

Ajka, Veszprém, Hungary

Location

Unknown Facility

Nagykanizsa, Zala County, Hungary

Location

Unknown Facility

Zalaegerszeg, Zala County, Hungary

Location

Unknown Facility

Tel Litwinsky, IL, Israel

Location

Unknown Facility

Safed, ISR, Israel

Location

Unknown Facility

Ofakim, South, Israel

Location

Unknown Facility

Holon, Israel

Location

Unknown Facility

Tel Litwinsky, Israel

Location

Unknown Facility

Skedsmokorset, Akershus, Norway

Location

Unknown Facility

Oslo, Norway

Location

Unknown Facility

Svidník, Presov, Slovakia

Location

Unknown Facility

Bratislava, SK, Slovakia

Location

Unknown Facility

Bratislava, SR, Slovakia

Location

Unknown Facility

Lučenec, Slovakia

Location

Unknown Facility

Považská Bystrica, Slovakia

Location

Unknown Facility

Worton Grange, Reading, Berkshire, United Kingdom

Location

Unknown Facility

Edgbaston, Birmingham, United Kingdom

Location

Unknown Facility

Llanishen, Cardiff, United Kingdom

Location

Unknown Facility

Choley, Lancashire, United Kingdom

Location

Unknown Facility

Waterloo, Liverpool, United Kingdom

Location

Unknown Facility

Lloyd Street North, Manchester, United Kingdom

Location

Unknown Facility

Glasgow, Scotland, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 32928709 DERIVED

• 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.

  PMID: 31166599 DERIVED

• 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.

  PMID: 27639753 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Results Point of Contact

• Title: Clinical Trial Management
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  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

Model Details: 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.

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: August 21, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: April 1, 2015
• Last Updated: March 21, 2017
• Results First Posted: March 21, 2017

Record last verified: 2017-01

Locations

US (49); CA (7); IL (5); SL (5); BU (2); HU (6); NO (2); GB (7)