Clinical trial NCT02107898: 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)
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Alirocumab in Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid Modifying Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2014-04-08
Enrollment: 216
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
timeFrame: From baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - ITT Analysis
timeFrame: Up to Week 24
measure: Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - On-Treatment Analysis
timeFrame: Up to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
measure: Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis
timeFrame: From Baseline to Week 24
Other outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
timeFrame: From Baseline to Week 52
measure: Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis
timeFrame: From Baseline to Week 52
Locations:
city: Adachi-Ku
country: Japan
facility: Investigational Site Number 392016
city: Adachi-Ku
country: Japan
facility: Investigational Site Number 392029
city: Aki-Gun
country: Japan
facility: Investigational Site Number 392024
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392012
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392013
city: Fukui-Shi
country: Japan
facility: Investigational Site Number 392032
city: Hakusan-Shi
country: Japan
facility: Investigational Site Number 392004
city: Kaga-Shi
country: Japan
facility: Investigational Site Number 392028
city: Kanazawa-Shi
country: Japan
facility: Investigational Site Number 392002
city: Kanazawa-Shi
country: Japan
facility: Investigational Site Number 392005
city: Kawanishi-Shi
country: Japan
facility: Investigational Site Number 392023
city: Kisarazu-Shi
country: Japan
facility: Investigational Site Number 392009
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 392026
city: Komatsu-Shi
country: Japan
facility: Investigational Site Number 392003
city: Kuki-Shi
country: Japan
facility: Investigational Site Number 392011
city: Matsumoto-Shi
country: Japan
facility: Investigational Site Number 392017
city: Mito-Shi
country: Japan
facility: Investigational Site Number 392007
city: Moriya-Shi
country: Japan
facility: Investigational Site Number 392006
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392018
city: Oota-Ku
country: Japan
facility: Investigational Site Number 392014
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392019
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392020
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392022
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392030
city: Oyabe-Shi
country: Japan
facility: Investigational Site Number 392027
city: Saitama-Shi
country: Japan
facility: Investigational Site Number 392010
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 392015
city: Shizuoka-Shi
country: Japan
facility: Investigational Site Number 392031
city: Suita-Shi
country: Japan
facility: Investigational Site Number 392021
city: Takamatsu-Shi
country: Japan
facility: Investigational Site Number 392025
city: Tsuchiura-Shi
country: Japan
facility: Investigational Site Number 392008
city: Yamagata-Shi
country: Japan
facility: Investigational Site Number 392001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.