Clinical trial NCT02984982: Evaluation of Effect of Alirocumab on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia
Official title: A Randomized, Open-label, Blinded Intravascular Ultrasound Analysis, Parallel Group, Multicenter Study to Evaluate the Effect of Praluent® (Alirocumab) on Coronary Atheroma Volume in Japanese Patients Hospitalized for Acute Coronary Syndrome With Hypercholesterolemia Not Adequately Controlled With Statin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypercholesterolemia
Acute Coronary Syndrome
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-12-07
Enrollment: 206
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percent Change From Baseline in Normalized Total Atheroma Volume (TAV) at Week 36
timeFrame: Baseline, Week 36
Secondary outcomes:
measure: Absolute Change From Baseline in Percent Atheroma Volume (PAV) at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Normalized Total Atheroma Volume at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in External Elastic Membrane (EEM) Volume at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in External Elastic Membrane Volume at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Lumen Volume at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in Lumen Volume at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36
timeFrame: Baseline, Week 12, Week 36
measure: Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol at Week 12 and Week 36
timeFrame: Baseline, Week 12, Week 36
measure: Absolute Change From Baseline in Apolipoprotein B (Apo B) at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in Apolipoprotein B at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Total Cholesterol (TC) at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in Total Cholesterol at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Lipoprotein (a) (Lp[a]) at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in Lipoprotein (a) at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in High-density Lipoprotein Cholesterol at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in High-density Lipoprotein Cholesterol at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Fasting Triglycerides (TGs) at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in Fasting Triglycerides at Week 36
timeFrame: Baseline, Week 36
measure: Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 36
timeFrame: Baseline, Week 36
measure: Percent Change From Baseline in Apolipoprotein A-1 at Week 36
timeFrame: Baseline, Week 36
measure: Number of Participants With Cardiovascular (CV) Adverse Events
timeFrame: Up to 36 weeks
Other outcomes:
Locations:
city: Bunkyō-Ku
country: Japan
facility: Investigational Site Number 392026
city: Chiyoda-ku
country: Japan
facility: Investigational Site Number 392022
city: Fujisawa-shi
country: Japan
facility: Investigational Site Number 392032
city: Fukui-shi
country: Japan
facility: Investigational Site Number 392004
city: Fukuoka-shi
country: Japan
facility: Investigational Site Number 392007
city: Fukuoka-shi
country: Japan
facility: Investigational Site Number 392048
city: Gifu-shi
country: Japan
facility: Investigational Site Number 392008
city: Hiroshima-shi
country: Japan
facility: Investigational Site Number 392039
city: Isehara-shi
country: Japan
facility: Investigational Site Number 392028
city: Itabashi-ku
country: Japan
facility: Investigational Site Number 392036
city: Itabashi-ku
country: Japan
facility: Investigational Site Number 392037
city: Izumisano-shi
country: Japan
facility: Investigational Site Number 392024
city: Izunokuni-shi
country: Japan
facility: Investigational Site Number 392013
city: Kawaguchi-shi
country: Japan
facility: Investigational Site Number 392020
city: Kitakyushu-shi
country: Japan
facility: Investigational Site Number 392009
city: Kitakyushu-shi
country: Japan
facility: Investigational Site Number 392034
city: Kochi-shi
country: Japan
facility: Investigational Site Number 392044
city: Kumamoto-shi
country: Japan
facility: Investigational Site Number 392002
city: Kumamoto-shi
country: Japan
facility: Investigational Site Number 392011
city: Kurashiki-shi
country: Japan
facility: Investigational Site Number 392003
city: Matsuyama-shi
country: Japan
facility: Investigational Site Number 392018
city: Morioka-shi
country: Japan
facility: Investigational Site Number 392021
city: Nagakute-shi
country: Japan
facility: Investigational Site Number 392017
city: Nagaoka-shi
country: Japan
facility: Investigational Site Number 392047
city: Okayama-shi
country: Japan
facility: Investigational Site Number 392033
city: Osaka-shi
country: Japan
facility: Investigational Site Number 392006
city: Osaka-shi
country: Japan
facility: Investigational Site Number 392010
city: Osaka-shi
country: Japan
facility: Investigational Site Number 392045
city: Osaka-shi
country: Japan
facility: Investigational Site Number 392046
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number 392015
city: Sakai-shi
country: Japan
facility: Investigational Site Number 392019
city: Sapporo-shi
country: Japan
facility: Investigational Site Number 392035
city: Tenri-shi
country: Japan
facility: Investigational Site Number 392001
city: Toyoake-shi
country: Japan
facility: Investigational Site Number 392016
city: Tsukuba-shi
country: Japan
facility: Investigational Site Number 392025
city: Tsukuba-shi
country: Japan
facility: Investigational Site Number 392040
city: Wakayama-shi
country: Japan
facility: Investigational Site Number 392005
city: Yokohama-shi
country: Japan
facility: Investigational Site Number 392027
city: Yokohama-shi
country: Japan
facility: Investigational Site Number 392043
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.