Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)

NCT ID: NCT02107898

Last Updated: 2016-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2015-09-30

Brief Summary

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable daily statin therapy with or without other lipid modifying therapy in comparison with placebo after 24 weeks of treatment in heterozygous familial hypercholesterolemia (HeFH) or high cardiovascular risk participants with hypercholesterolemia.

Secondary Objectives:

• To evaluate the effect of alirocumab in comparison with placebo on LDL-C after 12 weeks of treatment.
• To evaluate the effect of alirocumab on other lipid parameters.
• To evaluate the long-term effect of alirocumab in comparison with placebo on LDL-C after 52 weeks of treatment.
• To evaluate the safety and tolerability of alirocumab.
• To evaluate the development of anti-alirocumab antibodies.
• To evaluate the pharmacokinetics of alirocumab.

Detailed Description

Total duration per participant of approximately 63 weeks (14 months) (screening: 3 weeks, double-blind treatment period: 52 weeks, and follow-up period: 8 weeks).

Conditions

Hypercholesterolemia

Study Design

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

Study Groups

Placebo Q2W

Placebo (for alirocumab) every two weeks (Q2W) added to stable lipid-modifying therapy (LMT).

Group Type: PLACEBO_COMPARATOR

Placebo (for alirocumab)

Intervention Type: DRUG

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

Lipid-Modifying Therapy (LMT)

Intervention Type: DRUG

Statin (pravastatin, simvastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin) at stable dose with or without other LMT as clinically indicated.

Alirocumab 75 mg/Up to 150 mg Q2W

Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels above pre-specified threshold at Week 8 as defined in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012 i.e.

• ≥100 mg/dL (2.59 mmol/L) in heFH participants or in non-familial hypercholesterolemia (non-FH) participants who had a history of documented coronary heart disease (CHD)
• ≥120 mg/dL (3.10 mmol/L) in non-FH participants who had a history of documented diseases or other risk factors as categorized in primary prevention category III

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

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

Lipid-Modifying Therapy (LMT)

Intervention Type: DRUG

Statin (pravastatin, simvastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin) at stable dose with or without other LMT as clinically indicated.

Interventions

Placebo (for alirocumab)

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

Intervention Type: DRUG

Alirocumab

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

Intervention Type: DRUG

Lipid-Modifying Therapy (LMT)

Statin (pravastatin, simvastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin) at stable dose with or without other LMT as clinically indicated.

Intervention Type: DRUG

Other Intervention Names

SAR236553; REGN727; Praluent

Eligibility Criteria

Inclusion Criteria

Participants with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia who were not adequately controlled with a stable daily dose of statin with or without other lipid modifying therapy, at stable dose prior to the screening visit (Week -3).

Exclusion Criteria

1. LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit in participants with heterozygous familial hypercholesterolemia or in participants with non-familial hypercholesterolemia who had a history of documented coronary heart disease as described in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

2. LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit in participants with non-familial hypercholesterolemia who had a history of documented diseases or other risk factors as categorized in primary prevention category III as described in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

3. Not on a stable daily dose of lipid modifying therapy (including statin) within 4 weeks prior to the screening visit or between screening and randomization visits.

4. Age <20 years at the screening visit.

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 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 392016

Adachi-Ku, , Japan

Investigational Site Number 392029

Adachi-Ku, , Japan

Investigational Site Number 392024

Aki-Gun, , Japan

Investigational Site Number 392012

Chūōku, , Japan

Investigational Site Number 392013

Chūōku, , Japan

Investigational Site Number 392032

Fukui-shi, , Japan

Investigational Site Number 392004

Hakusan-Shi, , Japan

Investigational Site Number 392028

Kaga-Shi, , Japan

Investigational Site Number 392002

Kanazawa, , Japan

Investigational Site Number 392005

Kanazawa, , Japan

Investigational Site Number 392023

Kawanishi-Shi, , Japan

Investigational Site Number 392009

Kisarazu-Shi, , Japan

Investigational Site Number 392026

Kitakyushu-Shi, , Japan

Investigational Site Number 392003

Komatsu-Shi, , Japan

Investigational Site Number 392011

Kuki-Shi, , Japan

Investigational Site Number 392017

Matsumoto-Shi, , Japan

Investigational Site Number 392007

Mito, , Japan

Investigational Site Number 392006

Moriya-Shi, , Japan

Investigational Site Number 392018

Nagoya, , Japan

Investigational Site Number 392014

Oota-Ku, , Japan

Investigational Site Number 392019

Osaka, , Japan

Investigational Site Number 392020

Osaka, , Japan

Investigational Site Number 392022

Osaka, , Japan

Investigational Site Number 392030

Osaka, , Japan

Investigational Site Number 392027

Oyabe-Shi, , Japan

Investigational Site Number 392010

Saitama-Shi, , Japan

Investigational Site Number 392015

Shinjuku-Ku, , Japan

Investigational Site Number 392031

Shizuoka, , Japan

Investigational Site Number 392021

Suita-Shi, , Japan

Investigational Site Number 392025

Takamatsu, , Japan

Investigational Site Number 392008

Tsuchiura-Shi, , Japan

Investigational Site Number 392001

Yamagata, , Japan

Countries

Japan

References

Teramoto T, Kobayashi M, Tasaki H, Yagyu H, Higashikata T, Takagi Y, Uno K, Baccara-Dinet MT, Nohara A. Efficacy and Safety of Alirocumab in Japanese Patients With Heterozygous Familial Hypercholesterolemia or at High Cardiovascular Risk With Hypercholesterolemia Not Adequately Controlled With Statins - ODYSSEY JAPAN Randomized Controlled Trial. Circ J. 2016 Aug 25;80(9):1980-7. doi: 10.1253/circj.CJ-16-0387. Epub 2016 Jul 22.

Reference Type: RESULT

PMID: 27452202 (View on PubMed)

Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.

Reference Type: DERIVED

PMID: 33078867 (View on PubMed)

Other Identifiers

U1111-1115-7486

Identifier Type: OTHER

Identifier Source: secondary_id

EFC13672

Identifier Type: -

Identifier Source: org_study_id