Effect of Dalcetrapib on CV Risk in a Genetically Defined Population With a Recent ACS

Acute Coronary Syndrome Clinical Trial

— dal-GenE-2  

Official title:

Phase III, Double-blind, Randomized Placebo-controlled Study to Evaluate the Effects of Dalcetrapib on Cardiovascular (CV) Risk in a Genetically Defined Population With a Recent Acute Coronary Syndrome (ACS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05918861
• Other study ID #: DAL-302
• Status: Recruiting
• Phase: Phase 3
• Start date: October 3, 2023
• Est. completion date: August 2027

Study information

• Verified date: May 2024
• Source: DalCor Pharmaceuticals
• Contact: David Kallend, MBBS
• Phone: +41 79 174 1830
• Email: dkallend[@]dalcorpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: August 2027
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

Drug:
• Dalcetrapib
Cholesterol Ester Transfer Protein Inhibitor, 300 mg tablets
• Placebo
matching placebo tablets

Locations

Country	Name	City	State
Canada	Research Site	Abbotsford	British Columbia
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Burnaby	British Columbia
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Cambridge	Ontario
Canada	Research Site	Cambridge	Ontario
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Granby	Quebec
Canada	Research Site	Greenfield Park	Quebec City
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Kamloops	British Columbia
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Laval	Quebec
Canada	Research Site	Lévis	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Montréal	Quebec
Canada	Research Site	Montréal	Quebec
Canada	Research Site	Montréal	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	North Vancouver	British Columbia
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Québec	Quebec
Canada	Research Site	Québec	Quebec
Canada	Research Site	Rimouski	Quebec
Canada	Research Site	Saint Charles Borromee	Quebec
Canada	Research Site	Saint John's	New Foundland
Canada	Research Site	Saint-Jérôme	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Scarborough	Ontario
Canada	Research Site	Scarborough	Ontario
Canada	Research Site	Sherbrooke	Quebec City
Canada	Research Site	St-Hubert	Quebec
Canada	Research Site	Terrebonne	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-Rivières	Quebec
Canada	Research Site	Valleyfield	Quebec City
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Victoria	British Columbia
Canada	Research Site	Winnipeg	Manitoba
Puerto Rico	Research Site	Caguas
Puerto Rico	Research Site	Carolina
United States	Research Site	Acworth	Georgia
United States	Research Site	Alexander City	Alabama
United States	Research Site	Amarillo	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bangor	Maine
United States	Research Site	Beaumont	Texas
United States	Research Site	Bethesda	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boca Raton	Florida
United States	Research Site	Boca Raton	Florida
United States	Research Site	Bowie	Maryland
United States	Research Site	Bridgewater	New Jersey
United States	Research Site	Canton	Ohio
United States	Research Site	Chambersburg	Pennsylvania
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Coon Rapids	Minnesota
United States	Research Site	Cypress	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Dearborn	Michigan
United States	Research Site	Detroit	Michigan
United States	Research Site	Doral	Florida
United States	Research Site	Duluth	Minnesota
United States	Research Site	Fairhope	Alabama
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Garden Grove	California
United States	Research Site	Golden	Colorado
United States	Research Site	Greeneville	Tennessee
United States	Research Site	Hammond	Louisiana
United States	Research Site	Hazel Crest	Illinois
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Hialeah	Florida
United States	Research Site	Homestead	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntsville	Alabama
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jefferson City	Tennessee
United States	Research Site	Johnson City	New York
United States	Research Site	Jonesboro	Arkansas
United States	Research Site	Kingwood	Texas
United States	Research Site	Kissimmee	Florida
United States	Research Site	Largo	Florida
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lexington	Kentucky
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Loveland	Colorado
United States	Research Site	Mandeville	Louisiana
United States	Research Site	McKinney	Texas
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Midland	Michigan
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mobile	Alabama
United States	Research Site	Newburgh	Indiana
United States	Research Site	Norfolk	Virginia
United States	Research Site	North Little Rock	Arkansas
United States	Research Site	North Miami Beach	Florida
United States	Research Site	Nottingham	Maryland
United States	Research Site	Oak Ridge	Tennessee
United States	Research Site	Ocala	Florida
United States	Research Site	Park Ridge	Illinois
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Pensacola	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pinehurst	North Carolina
United States	Research Site	Pomona	New Jersey
United States	Research Site	Port Arthur	Texas
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Poughkeepsie	New York
United States	Research Site	Powell	Tennessee
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Indiana
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Rocky Mount	North Carolina
United States	Research Site	Safety Harbor	Florida
United States	Research Site	Saint Cloud	Minnesota
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Springfield	Ohio
United States	Research Site	Tallahassee	Florida
United States	Research Site	Toledo	Ohio
United States	Research Site	Torrance	California
United States	Research Site	Tucson	Arizona
United States	Research Site	Waco	Texas
United States	Research Site	West Des Moines	Iowa
United States	Research Site	West Hills	California
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Haven	Florida
United States	Research Site	Wyomissing	Pennsylvania
United States	Research Site	Ypsilanti	Michigan
United States	Research Site	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
DalCor Pharmaceuticals	The Montreal Health Innovations Coordinating Center (MHICC)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first occurrence of any fatal or non-fatal myocardial infarction (MI)	Time to patients experiencing major cardiovascular events	Average of 30 months from randomization
Secondary	The composite of all-cause death, resuscitated cardiac arrest, non-fatal MI and non-fatal stroke	Time to patients experiencing major cardiovascular events	Average of 30 months from randomization
Secondary	Composite of all-cause death, resuscitated cardiac arrest, non-fatal MI and non-fatal stroke	Time to patients experiencing first and recurrent occurrences	Average of 30 months from randomization
Secondary	Fatal and non-fatal MI	Time to patients experiencing first and recurrent occurrences	Average of 30 months from randomization