Clinical trial NCT01730053: Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II)
Official title: A Randomized, Double-Blind Study of the Efficacy and Safety of REGN727 Added-on to Rosuvastatin Versus Ezetimibe Added-on to Rosuvastatin Versus Rosuvastatin Dose Increase in Patients Who Are Not Controlled on Rosuvastatin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2012-11-21
Enrollment: 305
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: To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab (REGN727/SAR236553) as an add-on therapy to other LMT in patients with hypercholesterolemia at high cardiovascular (CV) risk.


Eligibility criteria: Inclusion Criteria:

1. Patients with LDL-C greater than or equal to 70 mg/dL at the screening visit and who are not adequately controlled with a stable daily dose of rosuvastatin, with or without other LMT.

   OR
2. Patients with screening LDL-C greater than or equal to 100 mg/dL who are not adequately controlled with a stable daily dose of rosuvastatin before the screening visit, with or without other LMT.

Exclusion Criteria:

1. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented cardiovascular disease (CVD)
2. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented coronary heart disease (CHD) or non-CHD CVD, but with other risk factors
3. Homozygous familial hypercholesterolemia (FH) (clinically or previous genotyping)
4. Recent (within 3 months prior to the screening visit) myocardial infarction (MI), unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
5. Newly diagnosed (within 3 months prior to randomization visit) or poorly controlled diabetes
6. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins

(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 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 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 From Baseline in HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Fasting Triglycerides at 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:
Locations:
city: Chandler
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Fair Oaks
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Northridge
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Milford
country: United States
state: Connecticut
city: Atlantis
country: United States
state: Florida
city: Bradenton
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Lakeland
country: United States
state: Florida
city: Miami
country: United States
facility: (2 Locations)
state: Florida
city: Oviedo
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Morton
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Newton
country: United States
state: Kansas
city: Overland Park
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Auburn
country: United States
state: Maine
city: Bethesda
country: United States
state: Maryland
city: Edina
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Olive Branch
country: United States
state: Mississippi
city: Port Gibson
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Butte
country: United States
state: Montana
city: Williamsville
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Warwick
country: United States
state: Rhode Island
city: Greer
country: United States
state: South Carolina
city: Summerville
country: United States
state: South Carolina
city: Kingsport
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Herston
country: Australia
city: New Lambton Heights
country: Australia
city: Perth
country: Australia
city: Sherwood
country: Australia
city: Woolloongabba
country: Australia
city: Brampton
country: Canada
state: Ontario
city: Burlington
country: Canada
state: Ontario
city: Etobicoke
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Thornhill
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Chicoutimi
country: Canada
state: Quebec
city: Dijon
country: France
city: Lille
country: France
city: Bad Oeynhausen
country: Germany
city: Berlin
country: Germany
city: Koeln
country: Germany
city: Regensburg
country: Germany
city: Ulm
country: Germany
city: Chieti
country: Italy
city: Genova
country: Italy
city: Napoli
country: Italy
city: Palermo
country: Italy
city: Roma
country: Italy
facility: (2 Locations)
city: Baja California
country: Mexico
city: Distrito Federal
country: Mexico
city: Guadalajara
country: Mexico
facility: (3 Locations)
city: Monterrey
country: Mexico
city: Zapopan Jalisco
country: Mexico
city: Barcelona
country: Spain
facility: (2 Locations)
city: Madrid
country: Spain
city: Santiago
country: Spain
city: Sevilla
country: Spain
city: West Bromwich
country: United Kingdom
state: West Midlands
city: Chester
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: 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.
citation: Farnier M, Jones P, Severance R, Averna M, Steinhagen-Thiessen E, Colhoun HM, Du Y, Hanotin C, Donahue S. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial. Atherosclerosis. 2016 Jan;244:138-46. doi: 10.1016/j.atherosclerosis.2015.11.010. Epub 2015 Nov 14.
citation: Robinson JG, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, Donahue S. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014 Oct;37(10):597-604. doi: 10.1002/clc.22327. Epub 2014 Sep 30.