A clinical trial in which the effects of dalcetrapib on heart and blood vessel risks will be compared against placebo in people who have specific genetic patterns and who have had a recent history of sudden, reduced blood flow to the heart: the dal-GenE trial

Phase 1

• Conditions: This study is investigating the cardiovascular morbidity and mortality (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction (MI) and non-fatal stroke) in subjects with a documented recent ACS and the AA genotype at variant rs1967309 in the ADCY9 gene.; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; MedDRA version: 20.0Level: PTClassification code 10051592Term: Acute coronary syndromeSystem Organ Class: 10007541 - Cardiac disorders

• Registration Number: EUCTR2015-003895-65-BG
• Lead Sponsor: DalCor Pharma UK Ltd, Leatherhead, Swiss Branch Zug

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-06-20
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 6000

Inclusion Criteria

Subjects with the appropriate genetic background and recently hospitalized for ACS (between 1 and 3 months following the index event), will be enrolled in this trial. ACS is defined as the occurrence of at least one of the following events:

Myocardial Infarction (MI)

Spontaneous MI

A diagnosis of a qualifying MI event will be defined by a rise and/or fall of cardiac biomarkers (preferably cardiac troponin) with at least one determination greater than the 99th percentile upper reference limit (URL) plus at least one of the following described below:

•Symptoms of myocardial ischemia, or
•New or presumed new significant ST-segment-T wave (ST-T) changes or new left bundle branch block, or
•Development of pathological Q waves in the ECG, or
•Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, or
•Identification of an intracoronary thrombus by angiography

Procedure-Related MI after Percutaneous Coronary Intervention (PCI)

A procedure-related MI after PCI is defined as an increase of cardiac troponin values with at least one determination greater than 5 times the 99th percentile URL in patients with normal baseline values (less than or equal to 99th percentile URL) or a rise of cardiac troponin values > 20% if the baseline values are elevated and are stable or falling; plus at least one of the following described below:

•Symptoms suggestive of myocardial ischemia
•New ischemic ECG changes
•Imaging demonstration of new loss of viable myocardium or new regional wall motion abnormality
•Angiographic findings consistent with a procedural complication

Hospitalization for ACS (ECG Abnormalities without Biomarkers):

A diagnosis of a qualifying ACS event without increases in cardiac biomarkers will require admission to hospital or emergency room (exceeding 23 hrs) with symptoms presumed to be caused by myocardial ischemia with an accelerating tempo in the prior 48 hrs and/or prolonged (at least 20 min) rest chest discomfort and new ECG findings (or presumed new if no prior ECG available) as described below and at least one of the following:

•at least 50% stenosis of an epicardial coronary artery
•positive exercise or pharmacologic stress indicating reversible ischemia
•presence of pathologic Q-waves on ECG

Examples of New ECG findings include:
•New or presumed new ST depression of at least 0.5mm in at least 2 contiguous leads or T wave inversion of at least 1mm in leads with predominant R wave or R/S >1 in at least 2 contiguous leads
•New or presumed new ST elevation at the J point in = 2 contiguous leads with the following cut-off points: = 0.2mV in men or = 0.15mV in women in leads V2-V3 and/or =0.1 mV in other leads or new or presumed new left bundle branch block (LBBB)
•New tall R wave of at least 40ms in V1 and/or V2 and R/S = 1 in V1 with concordant positive T-wave in the absence of a conduction defect
•New Q waves = 30 ms wide and at least 1mm deep in any 2 leads of a contiguous lead grouping or Q wave >20ms or QS complex in leads V2 and V3 (these criteria also apply to silent MI detected during a routine follow-up visit)

In addition, the following inclusion criteria apply:

1. Both male and female subjects age 45 years and over at screening visit (V1)
2. Signed informed consent (approved by Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
3. AA genotype at variant rs 1967309 in the A

Exclusion Criteria

1. Females who are pregnant (negative pregnancy test required for all women of child-bearing potential at Visit 2, Day 0) or breast-feeding
2. 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 method of contraception.
3. New York Heart Association (NYHA) Class III or IV heart failure
4. Last known hemoglobin <10 g/dL
5. Index ACS event presumed due to uncontrolled hypertension
6. Systolic blood pressure (BP) >180 mmHg and/or diastolic blood pressure >110 mmHg by the time of randomization despite anti-hypertensive therapy
7. Last known serum triglyceride level > 500 mg/dL (> 5.65 mmol/L) as assessed within 6 months prior to randomization
8. Last known hemoglobin A1c (HbA1c) >10% as assessed within 6 months prior to randomization
9. Subjects with clinically apparent liver disease, eg, jaundice, cholestasis, hepatic synthetic impairment, or active hepatitis
10. Last known ALT or AST level > 3 times the upper limit of normal (ULN) or last known alkaline phosphatase level > 2 times the ULN as assessed within 6 months prior to randomization (excluding index event)
11. History of persistent and unexplained creatine phosphokinase (CPK) levels > 3 times the ULN as assessed within 6 months prior to randomization (excluding index event)
12. Last known serum creatinine > 2.2 mg/dL (195 µmol/l) as assessed within 6 months prior to randomization
13. Previous exposure to anacetrapib or evacetrapib or documented allergic reaction to any CETP inhibitor
14. History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 1 year prior to the screening
15. Any clinically significant medical condition that according to the investigator could interfere with the conduct of the study
16. Subjects whose life expectancy is shorter than 3 years
17. 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
18. Current alcohol or drug abuse or history thereof within 2 years prior to screening that would likely interfere with compliance, based on investigator assessment
19. 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
20. Subjects unable or unwilling to comply with protocol requirements, or deemed by the investigator to be unfit for the study
21. Subjects who have undergone coronary artery bypass graft (CABG) surgery between the index event and randomization

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified