Overview
This is a placebo-controlled, randomized, double-blind, parallel group, phase 3 multicenter study in subjects recently hospitalized for ACS and with the appropriate genetic profile. Subjects will provide informed consent before any study-specific procedures are performed. A separate informed consent will be allowed for an initial pre-screening genetic testing. Subjects meeting the AA genotype will then consent to the full study and confirmatory genetic testing as required. Subject enrollment may begin in the hospital and will continue following release from the hospital or may begin following release from hospital. Screening procedures may be performed at the time of the index ACS event or anytime thereafter, with the condition that randomization must occur within the mandated window (up to12 weeks after the index event). Subjects will be assessed based on their medical history. Those who are likely to qualify will undergo Genotype Assay testing to evaluate genetic determination for the presence of AA genotype.
Description
This is an event-driven study and will last until approximately 200 subjects have experienced a primary event, unless the study is stopped at the planned interim analysis. Visits after randomization will be performed as virtual visits where permissible every 3 months or as clinic visits until the study is stopped. For any subject prematurely discontinuing study medication, assessments will be conducted every 3 months for the collection of study endpoints.
Those who are likely to qualify will undergo Genotype Assay Testing to evaluate genetic determination or the presence of the AA genotype at variant rs 1967309 in the ADCY9 gene as determined by the investigational use only version of the cobas ADCY9 Genotype Test, conducted at a designated investigational testing site.
Eligibility
Inclusion Criteria:
- Subjects with the appropriate genetic background and recently hospitalized for ACS (up to 3 months following the index event), will be enrolled in this trial.
- Both male and female subjects age 45 years and over at screening visit (V1)
- AA genotype at variant gene as determined by Genotype Assay Test, conducted at a designated investigational testing site (ITS)
- Clinically stable, ie, free of ischemic symptoms at rest or with minimal exertion for at least 1 week prior to randomization
- Prior to randomization, subjects must have evidence of guidelines-based management of LDL-C, at a minimum to include medical and dietary treatment.
- Randomization within 3 months of the index ACS event
Exclusion Criteria:
- Females who are pregnant (negative urine pregnancy test required for all women of child-bearing potential at Visit 2, Day 0) or breast-feeding
- Women of childbearing potential (women who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using at least one highly effective method of contraception.
- New York Heart Association (NYHA) Class III or IV heart failure
- Index ACS event presumed due to uncontrolled hypertension
- Systolic blood pressure (BP) >180 mmHg and/or diastolic blood pressure >110 mmHg at the time of randomization despite anti-hypertensive therapy
- Subjects with clinically apparent liver disease, eg, jaundice, cholestasis, hepatic synthetic impairment, active hepatitis or last known ALT or AST level >3 x ULN within 6 months prior to randomization (excluding index event)
- History of persistent and unexplained creatine phosphokinase (CPK) levels > 5 times the ULN as assessed within 6 months prior to randomization (excluding index event)
- Last known eGFR < 30 mL/min/1.73m2 as assessed within 6 months prior to randomization
- History of malignancy or any other significant comorbidity, the prognosis or management of which is likely to interfere with study conduct or subjects with a life expectancy of less than 3 years.
- Presence of any last known laboratory value as evaluated prior to randomization that is considered by the investigator to potentially limit the patient's successful participation in the study
- Subjects who have received any investigational drug within 1 month of randomization, or who expect to participate in any other investigational drug or device study during the conduct of this trial
- Subjects who have undergone coronary artery bypass graft (CABG) surgery between the index event and randomization