Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II)

NCT ID: NCT02023879

Last Updated: 2018-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 233 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-16
• Study Completion Date: 2017-06-30

Brief Summary

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by a regimen of Alirocumab including a starting dose of 150 mg every 4 weeks (Q4W) as add-on to non-statin lipid modifying background therapy or as monotherapy in comparison with placebo in participants with primary hypercholesterolemia not treated with a statin.

Secondary Objective:

• To evaluate the effects on other lipid parameters of Alirocumab 150 mg Q4W versus placebo.
• To evaluate the safety and tolerability of Alirocumab 150 mg Q4W.

Alirocumab 75 mg Q2W was added as a calibrator arm.

Detailed Description

The core study duration was approximately 35 weeks per participant (screening: 3 weeks, double-blind treatment period: 24 weeks; follow-up: 8 weeks). Participants who successfully completed the treatment period had the possibility to participate in an optional open-label treatment period with Alirocumab 150 mg Q4W until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo Q2W

Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks.

Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.

Group Type: PLACEBO_COMPARATOR

Alirocumab

Intervention Type: DRUG

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Placebo (for Alirocumab)

Intervention Type: DRUG

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Non-statin LMT

Intervention Type: DRUG

Ezetimibe or Fenofibrate at stable dose as background therapy.

Diet Alone

Intervention Type: OTHER

Stable cholesterol-lowering diet as background therapy.

Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator)

Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.

Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Group Type: OTHER

Alirocumab

Intervention Type: DRUG

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Non-statin LMT

Intervention Type: DRUG

Ezetimibe or Fenofibrate at stable dose as background therapy.

Diet Alone

Intervention Type: OTHER

Stable cholesterol-lowering diet as background therapy.

Alirocumab 150 mg Q4W/Up to 150 mg Q2W

Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or <30% LDL-C reduction from baseline.

Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Placebo (for Alirocumab)

Intervention Type: DRUG

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Non-statin LMT

Intervention Type: DRUG

Ezetimibe or Fenofibrate at stable dose as background therapy.

Diet Alone

Intervention Type: OTHER

Stable cholesterol-lowering diet as background therapy.

Interventions

Alirocumab

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Intervention Type: DRUG

Placebo (for Alirocumab)

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Intervention Type: DRUG

Non-statin LMT

Ezetimibe or Fenofibrate at stable dose as background therapy.

Intervention Type: DRUG

Diet Alone

Stable cholesterol-lowering diet as background therapy.

Intervention Type: OTHER

Other Intervention Names

SAR236553; REGN727; Praluent®

Eligibility Criteria

Inclusion Criteria

Participants with primary hypercholesterolemia (heterozygous familial hypercholesterolemia [heFH] or non-FH) not adequately controlled with their non-statin LMT (either ezetimibe or fenofibrate) or diet alone.

Exclusion Criteria

• LDL-C <70 mg/dL (1.81 mmol/L) at screening for statin intolerant participants at very high cardiovascular (CV) risk;
• LDL-C <100 mg/dL (<2.59 mmol/L) at screening for statin intolerant participants at high or moderate CV risk or, participants not fulfilling the statin intolerant definition at moderate CV risk;
• LDL-C ≥160 mg/dL (≥4.1 mmol/L) at screening for participants receiving diet only or, participants not fulfilling the statin intolerant definition at moderate CV risk and receiving a non-statin LMT.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840703

Beverly Hills, California, United States

Investigational Site Number 840704

Atlantis, Florida, United States

Investigational Site Number 840708

Jacksonville, Florida, United States

Investigational Site Number 840701

Sarasota, Florida, United States

Investigational Site Number 840706

Fall River, Massachusetts, United States

Investigational Site Number 840705

St Louis, Missouri, United States

Investigational Site Number 840707

Durham, North Carolina, United States

Investigational Site Number 840702

Summerville, South Carolina, United States

Investigational Site Number 036703

Ashford, , Australia

Investigational Site Number 036702

Perth, , Australia

Investigational Site Number 036701

Woolloongabba, , Australia

Investigational Site Number 056702

Antwerp, , Belgium

Investigational Site Number 056703

Haine-Saint-Paul, , Belgium

Investigational Site Number 056701

Leuven, , Belgium

Investigational Site Number 124703

Chicoutimi, , Canada

Investigational Site Number 124701

Québec, , Canada

Investigational Site Number 124704

Sherbrooke, , Canada

Investigational Site Number 124706

Toronto, , Canada

Investigational Site Number 124702

Vancouver, , Canada

Investigational Site Number 124705

Victoria, , Canada

Investigational Site Number 208703

Aarhus, , Denmark

Investigational Site Number 208702

Esbjerg, , Denmark

Investigational Site Number 208701

Glostrup Municipality, , Denmark

Investigational Site Number 208704

Hvidovre, , Denmark

Investigational Site Number 208705

Køge, , Denmark

Investigational Site Number 528701

Amsterdam, , Netherlands

Investigational Site Number 528708

Den Helder, , Netherlands

Investigational Site Number 528702

Hoogeveen, , Netherlands

Investigational Site Number 528703

Hoorn, , Netherlands

Investigational Site Number 528706

Rotterdam, , Netherlands

Investigational Site Number 528709

Sneek, , Netherlands

Investigational Site Number 528704

Utrecht, , Netherlands

Investigational Site Number 528707

Venlo, , Netherlands

Investigational Site Number 554702

Auckland, , New Zealand

Investigational Site Number 554701

Christchurch, , New Zealand

Investigational Site Number 724703

A Coruña, , Spain

Investigational Site Number 724707

Barcelona, , Spain

Investigational Site Number 724710

Barcelona, , Spain

Investigational Site Number 724702

Córdoba, , Spain

Investigational Site Number 724705

Granada, , Spain

Investigational Site Number 724709

Sant Joan Despí, , Spain

Investigational Site Number 724706

Santiago de Compostela, , Spain

Investigational Site Number 724701

Zaragoza, , Spain

Countries

United States; Australia; Belgium; Canada; Denmark; Netherlands; New Zealand; Spain

References

Stroes E, Guyton JR, Lepor N, Civeira F, Gaudet D, Watts GF, Baccara-Dinet MT, Lecorps G, Manvelian G, Farnier M; ODYSSEY CHOICE II Investigators. Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study. J Am Heart Assoc. 2016 Sep 13;5(9):e003421. doi: 10.1161/JAHA.116.003421.

Reference Type: RESULT

PMID: 27625344 (View on PubMed)

Other Identifiers

2013-002659-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1146-3517

Identifier Type: OTHER

Identifier Source: secondary_id

EFC13786

Identifier Type: -

Identifier Source: org_study_id