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

NCT02984982 | Completed Phase 4 Results

• 2 other identifiers: ALIROL08069U1111-1184-8764
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 39

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.

Conditions

Hypercholesterolemia; Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36

  Least-squares (LS) means and standard errors (SE) at Week 36 were obtained from analysis of covariance (ANCOVA) model including treatment arm (SoC arm, alirocumab arm) and randomization strata (statin at ACS onset \[Yes / No\]) as fixed categorical effects, and the baseline normalized TAV as continuous fixed covariate.

  Baseline, Week 36

Secondary Outcomes (23)

• Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36

  Baseline, Week 36

• Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36

  Baseline, Week 36

• Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36

  Baseline, Week 36

• Percent Change From Baseline in External Elastic Membrane Volume at Week 36

  Baseline, Week 36

• Absolute Change From Baseline in Lumen Volume at Week 36

  Baseline, Week 36

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

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).

Drug: Atorvastatin; Drug: Rosuvastatin; Drug: Fenofibrate; Drug: Bezafibrate; Drug: Ezetimibe; Drug: Antiplatelets; Drug: Anticoagulants

Alirocumab

EXPERIMENTAL

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.

Drug: Alirocumab SAR236553; Drug: Atorvastatin; Drug: Rosuvastatin; Drug: Fenofibrate; Drug: Bezafibrate; Drug: Ezetimibe; Drug: Antiplatelets; Drug: Anticoagulants

Interventions

Alirocumab SAR236553 DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Also known as: Praluent

Alirocumab

Atorvastatin DRUG

Pharmaceutical form: tablet Route of administration: oral

Alirocumab; Standard of Care

Rosuvastatin DRUG

Pharmaceutical form: tablet Route of administration: oral

Alirocumab; Standard of Care

Fenofibrate DRUG

Pharmaceutical form: tablet Route of administration: oral

Alirocumab; Standard of Care

Bezafibrate DRUG

Pharmaceutical form: tablet Route of administration: oral

Alirocumab; Standard of Care

Ezetimibe DRUG

Pharmaceutical form: tablet Route of administration: oral

Alirocumab; Standard of Care

Antiplatelets DRUG

Pharmaceutical form: tablet or capsule Route of administration: oral

Alirocumab; Standard of Care

Anticoagulants DRUG

Pharmaceutical form: tablet or capsule Route of administration: oral

Alirocumab; Standard of Care

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (39)

Investigational Site Number 392026

Bunkyō City, Japan

Location

Investigational Site Number 392022

Chiyoda-ku, Japan

Location

Investigational Site Number 392032

Fujisawa-shi, Japan

Location

Investigational Site Number 392004

Fukui-shi, Japan

Location

Investigational Site Number 392007

Fukuoka, Japan

Location

Investigational Site Number 392048

Fukuoka, Japan

Location

Investigational Site Number 392008

Gifu, Japan

Location

Investigational Site Number 392039

Hiroshima, Japan

Location

Investigational Site Number 392028

Isehara-shi, Japan

Location

Investigational Site Number 392036

Itabashi-ku, Japan

Location

Investigational Site Number 392037

Itabashi-ku, Japan

Location

Investigational Site Number 392024

Izumisano, Japan

Location

Investigational Site Number 392013

Izunokuni-shi, Japan

Location

Investigational Site Number 392020

Kawaguchi-shi, Japan

Location

Investigational Site Number 392009

Kitakyushu-shi, Japan

Location

Investigational Site Number 392034

Kitakyushu-shi, Japan

Location

Investigational Site Number 392044

Kochi, Japan

Location

Investigational Site Number 392002

Kumamoto, Japan

Location

Investigational Site Number 392011

Kumamoto, Japan

Location

Investigational Site Number 392003

Kurashiki-shi, Japan

Location

Investigational Site Number 392018

Matsuyama, Japan

Location

Investigational Site Number 392021

Morioka, Japan

Location

Investigational Site Number 392017

Nagakute-shi, Japan

Location

Investigational Site Number 392047

Nagaoka-shi, Japan

Location

Investigational Site Number 392033

Okayama, Japan

Location

Investigational Site Number 392006

Osaka, Japan

Location

Investigational Site Number 392010

Osaka, Japan

Location

Investigational Site Number 392045

Osaka, Japan

Location

Investigational Site Number 392046

Osaka, Japan

Location

Investigational Site Number 392015

Sagamihara-shi, Japan

Location

Investigational Site Number 392019

Sakaishi, Japan

Location

Investigational Site Number 392035

Sapporo, Japan

Location

Investigational Site Number 392001

Tenri-shi, Japan

Location

Investigational Site Number 392016

Toyoake-shi, Japan

Location

Investigational Site Number 392025

Tsukuba, Japan

Location

Investigational Site Number 392040

Tsukuba, Japan

Location

Investigational Site Number 392005

Wakayama, Japan

Location

Investigational Site Number 392027

Yokohama, Japan

Location

Investigational Site Number 392043

Yokohama, Japan

Location

Related Publications (2)

• 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.

  PMID: 31434809 DERIVED

• 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.

  PMID: 29606415 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Acute Coronary Syndrome

Interventions

alirocumab; Atorvastatin; Rosuvastatin Calcium; Fenofibrate; Bezafibrate; Ezetimibe; Anticoagulants

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Phenols; Ketones; Benzamides; Benzoates; Acids, Carbocyclic; Chlorobenzoates; Azetidines; Azetines; Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 7, 2016
• Study Start: November 15, 2016
• Primary Completion: July 27, 2018
• Study Completion: July 27, 2018
• Last Updated: September 9, 2019
• Results First Posted: September 9, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (39)