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)

NCT02107898 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC13672U1111-1115-7486
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 32

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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)

  Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

  From Baseline to Week 24

Secondary Outcomes (21)

• Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis

  From baseline to Week 24

• Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis

  From Baseline to Week 24

Other Outcomes (2)

• Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis

  From Baseline to Week 52

• Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis

  From Baseline to Week 52

Study Arms (2)

Placebo Q2W

PLACEBO COMPARATOR

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

Drug: Placebo (for alirocumab); Drug: Lipid-Modifying Therapy (LMT)

Alirocumab 75 mg/Up to 150 mg Q2W

EXPERIMENTAL

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

Drug: Alirocumab; Drug: Lipid-Modifying Therapy (LMT)

Interventions

Placebo (for alirocumab) DRUG

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

Placebo Q2W

Alirocumab DRUG

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

Also known as: SAR236553, REGN727, Praluent

Alirocumab 75 mg/Up to 150 mg Q2W

Lipid-Modifying Therapy (LMT) 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; Placebo Q2W

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (32)

Investigational Site Number 392016

Adachi-Ku, Japan

Location

Investigational Site Number 392029

Adachi-Ku, Japan

Location

Investigational Site Number 392024

Aki-Gun, Japan

Location

Investigational Site Number 392012

Chūōku, Japan

Location

Investigational Site Number 392013

Chūōku, Japan

Location

Investigational Site Number 392032

Fukui-shi, Japan

Location

Investigational Site Number 392004

Hakusan-Shi, Japan

Location

Investigational Site Number 392028

Kaga-Shi, Japan

Location

Investigational Site Number 392002

Kanazawa, Japan

Location

Investigational Site Number 392005

Kanazawa, Japan

Location

Investigational Site Number 392023

Kawanishi-Shi, Japan

Location

Investigational Site Number 392009

Kisarazu-Shi, Japan

Location

Investigational Site Number 392026

Kitakyushu-Shi, Japan

Location

Investigational Site Number 392003

Komatsu-Shi, Japan

Location

Investigational Site Number 392011

Kuki-Shi, Japan

Location

Investigational Site Number 392017

Matsumoto-Shi, Japan

Location

Investigational Site Number 392007

Mito, Japan

Location

Investigational Site Number 392006

Moriya-Shi, Japan

Location

Investigational Site Number 392018

Nagoya, Japan

Location

Investigational Site Number 392014

Oota-Ku, Japan

Location

Investigational Site Number 392019

Osaka, Japan

Location

Investigational Site Number 392020

Osaka, Japan

Location

Investigational Site Number 392022

Osaka, Japan

Location

Investigational Site Number 392030

Osaka, Japan

Location

Investigational Site Number 392027

Oyabe-Shi, Japan

Location

Investigational Site Number 392010

Saitama-Shi, Japan

Location

Investigational Site Number 392015

Shinjuku-Ku, Japan

Location

Investigational Site Number 392031

Shizuoka, Japan

Location

Investigational Site Number 392021

Suita-Shi, Japan

Location

Investigational Site Number 392025

Takamatsu, Japan

Location

Investigational Site Number 392008

Tsuchiura-Shi, Japan

Location

Investigational Site Number 392001

Yamagata, Japan

Location

Related Publications (2)

• 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.

  PMID: 27452202 RESULT

• 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.

  PMID: 33078867 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2014
• First Posted: April 8, 2014
• Study Start: March 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: September 1, 2015
• Last Updated: October 4, 2016
• Results First Posted: January 29, 2016

Record last verified: 2016-09

Locations

JP (32)