Evaluation of Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia

NCT ID: NCT02984982

Last Updated: 2019-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-15
• Study Completion Date: 2018-07-27

Brief Summary

Primary Objective:

To compare the efficacy of alirocumab (Praluent®) with standard of care (SoC) on coronary atheroma progression (percent change in normalized total atheroma volume [TAV]) after 9 months of treatment in participants who had acute coronary syndrome (ACS) within 4 weeks prior to randomization, with hypercholesterolemia treated with statin.

Secondary Objectives:

• To compare the efficacy of alirocumab (Praluent®) with SoC on secondary endpoints including absolute change in percent atheroma volume and normalized TAV after 9 months of treatment.
• To evaluate the efficacy of alirocumab (Praluent®) on low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, triglycerides, non-high-density lipoprotein cholesterol and lipoprotein (a) after 9 months treatment.
• To evaluate the safety of alirocumab (Praluent®) including the occurrence of cardiovascular events (coronary heart disease death, non-fatal myocardial infarction, fatal and non-fatal ischemic stroke, unstable angina requiring hospitalization) throughout the study.

Detailed Description

The duration of study per participant was 9 months.

Conditions

Hypercholesterolemia; Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of Care

Statin therapy (atorvastatin or rosuvastatin) will be administered with or without non-statin lipid modifying therapies (LMTs). Non-statin LMTs will be adjusted by physicians to achieve the LDL-C target level \<100 milligrams per deciliter (mg/dL).

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Rosuvastatin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Fenofibrate

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Bezafibrate

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Ezetimibe

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Antiplatelets

Intervention Type: DRUG

Pharmaceutical form: tablet or capsule

Route of administration: oral

Anticoagulants

Intervention Type: DRUG

Pharmaceutical form: tablet or capsule

Route of administration: oral

Alirocumab

Alirocumab will be given subcutaneously every 2 weeks on top of stable dose statin therapy (atorvastatin or rosuvastatin) with or without stable dose non-statin LMTs.

Group Type: EXPERIMENTAL

Alirocumab SAR236553

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Atorvastatin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Rosuvastatin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Fenofibrate

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Bezafibrate

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Ezetimibe

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Antiplatelets

Intervention Type: DRUG

Pharmaceutical form: tablet or capsule

Route of administration: oral

Anticoagulants

Intervention Type: DRUG

Pharmaceutical form: tablet or capsule

Route of administration: oral

Interventions

Alirocumab SAR236553

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Intervention Type: DRUG

Atorvastatin

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Rosuvastatin

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Fenofibrate

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Bezafibrate

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Ezetimibe

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Antiplatelets

Pharmaceutical form: tablet or capsule

Route of administration: oral

Intervention Type: DRUG

Anticoagulants

Pharmaceutical form: tablet or capsule

Route of administration: oral

Intervention Type: DRUG

Other Intervention Names

Praluent

Eligibility Criteria

Inclusion Criteria

• Participants hospitalized for ACS (Acute ST-segment elevation myocardial infarction [STEMI], Acute non-ST-segment elevation myocardial infarction [NSTEMI], and unstable angina.
• LDL-C >=100 mg/dL at ACS diagnosis.
• Participants who has stenosis with at least >50% stenosis angiographically within 1 week after the ACS onset, and has analyzable coronary intravascular Ultrasound image.
• Participants aged >=20 years old at ACS diagnosis.
• Negative Hepatitis B surface antigen, negative Hepatitis B core antibody, and negative Hepatitis C antibody. Or, negative Hepatitis B surface antigen, positive Hepatitis B core antibody, negative Hepatitis B deoxyribonucleic acid, and negative Hepatitis C antibody.
• Written informed consent.

Exclusion Criteria

• Participants who had previously treated with at least one dose of any anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody.
• Uncontrolled hypertension (multiple reading with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) between ACS diagnosis and randomization visit.
• Known history of hemorrhagic stroke.
• Currently under treatment for cancer.
• Participants on LDL apheresis.
• Any clinically significant abnormality identified that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, participants with short life expectancy.
• Considered by the Investigator or any sub-Investigator as inappropriate for this study for any reason, including:

• Unable to meet specific protocol requirements, such as scheduled visits;
• Investigator or any sub-Investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc;
• Presence of any other conditions (eg, geographic, social, etc.) actual or anticipated, that the Investigator feels would restrict or limit the participant's participation for the duration of the study.
• Laboratory findings measured within 4 weeks after the ACS diagnosis (positive serum or urine pregnancy test in females of childbearing potential).

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

• Minimum Eligible Age: 20 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 392026

Bunkyō City, , Japan

Investigational Site Number 392022

Chiyoda-ku, , Japan

Investigational Site Number 392032

Fujisawa-shi, , Japan

Investigational Site Number 392004

Fukui-shi, , Japan

Investigational Site Number 392007

Fukuoka, , Japan

Investigational Site Number 392048

Fukuoka, , Japan

Investigational Site Number 392008

Gifu, , Japan

Investigational Site Number 392039

Hiroshima, , Japan

Investigational Site Number 392028

Isehara-shi, , Japan

Investigational Site Number 392036

Itabashi-ku, , Japan

Investigational Site Number 392037

Itabashi-ku, , Japan

Investigational Site Number 392024

Izumisano, , Japan

Investigational Site Number 392013

Izunokuni-shi, , Japan

Investigational Site Number 392020

Kawaguchi-shi, , Japan

Investigational Site Number 392009

Kitakyushu-shi, , Japan

Investigational Site Number 392034

Kitakyushu-shi, , Japan

Investigational Site Number 392044

Kochi, , Japan

Investigational Site Number 392002

Kumamoto, , Japan

Investigational Site Number 392011

Kumamoto, , Japan

Investigational Site Number 392003

Kurashiki-shi, , Japan

Investigational Site Number 392018

Matsuyama, , Japan

Investigational Site Number 392021

Morioka, , Japan

Investigational Site Number 392017

Nagakute-shi, , Japan

Investigational Site Number 392047

Nagaoka-shi, , Japan

Investigational Site Number 392033

Okayama, , Japan

Investigational Site Number 392006

Osaka, , Japan

Investigational Site Number 392010

Osaka, , Japan

Investigational Site Number 392045

Osaka, , Japan

Investigational Site Number 392046

Osaka, , Japan

Investigational Site Number 392015

Sagamihara-shi, , Japan

Investigational Site Number 392019

Sakaishi, , Japan

Investigational Site Number 392035

Sapporo, , Japan

Investigational Site Number 392001

Tenri-shi, , Japan

Investigational Site Number 392016

Toyoake-shi, , Japan

Investigational Site Number 392025

Tsukuba, , Japan

Investigational Site Number 392040

Tsukuba, , Japan

Investigational Site Number 392005

Wakayama, , Japan

Investigational Site Number 392027

Yokohama, , Japan

Investigational Site Number 392043

Yokohama, , Japan

Countries

Japan

References

Ako J, Hibi K, Tsujita K, Hiro T, Morino Y, Kozuma K, Shinke T, Otake H, Uno K, Louie MJ, Takagi Y, Miyauchi K. Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients With Acute Coronary Syndrome - The ODYSSEY J-IVUS Trial. Circ J. 2019 Sep 25;83(10):2025-2033. doi: 10.1253/circj.CJ-19-0412. Epub 2019 Aug 20.

Reference Type: DERIVED

PMID: 31434809 (View on PubMed)

Ako J, Hibi K, Kozuma K, Miyauchi K, Morino Y, Shinke T, Tsujita K, Uno K, Kawabata Y, Hiro T. Effect of alirocumab on coronary atheroma volume in Japanese patients with acute coronary syndromes and hypercholesterolemia not adequately controlled with statins: ODYSSEY J-IVUS rationale and design. J Cardiol. 2018 Jun;71(6):583-589. doi: 10.1016/j.jjcc.2017.11.013. Epub 2018 Mar 30.

Reference Type: DERIVED

PMID: 29606415 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1184-8764

Identifier Type: OTHER

Identifier Source: secondary_id

ALIROL08069

Identifier Type: -

Identifier Source: org_study_id