Clinical trial NCT05918861: Effect of Dalcetrapib on CV Risk in a Genetically Defined Population With a Recent ACS
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Lead sponsor: DalCor Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: The Montreal Health Innovations Coordinating Center (MHICC)
First posted: 2023-06-26
Enrollment: 2000
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled, randomized, double-blind, parallel group, multi-center
Primary purpose: TREATMENT

Brief 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.

Detailed 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 criteria: 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

Primary outcomes:
measure: Time to first occurrence of any fatal or non-fatal myocardial infarction (MI)
timeFrame: Average of 30 months from randomization
Secondary outcomes:
measure: The composite of all-cause death, resuscitated cardiac arrest, non-fatal MI and non-fatal stroke
timeFrame: Average of 30 months from randomization
measure: Composite of all-cause death, resuscitated cardiac arrest, non-fatal MI and non-fatal stroke
timeFrame: Average of 30 months from randomization
measure: Fatal and non-fatal MI
timeFrame: Average of 30 months from randomization
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Fairhope
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Jonesboro
country: United States
facility: Research Site
state: Arkansas
city: North Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Garden Grove
country: United States
facility: Research Site
state: California
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: West Hills
country: United States
facility: Research Site
state: California
city: Golden
country: United States
facility: Research Site
state: Colorado
city: Hartford
country: United States
facility: Research Site
state: Connecticut
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Doral
country: United States
facility: Research Site
state: Florida
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Homestead
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Largo
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Pensacola
country: United States
facility: Research Site
state: Florida
city: Port Charlotte
country: United States
facility: Research Site
state: Florida
city: Safety Harbor
country: United States
facility: Research Site
state: Florida
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Tallahassee
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Winter Haven
country: United States
facility: Research Site
state: Florida
city: Acworth
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Gainesville
country: United States
facility: Research Site
state: Georgia
city: Bloomingdale
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Glenview
country: United States
facility: Research Site
state: Illinois
city: Hazel Crest
country: United States
facility: Research Site
state: Illinois
city: Park Ridge
country: United States
facility: Research Site
state: Illinois
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Merrillville
country: United States
facility: Research Site
state: Indiana
city: Newburgh
country: United States
facility: Research Site
state: Indiana
city: Richmond
country: United States
facility: Research Site
state: Indiana
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: West Des Moines
country: United States
facility: Research Site
state: Iowa
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Edgewood
country: United States
facility: Research Site
state: Kentucky
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Hammond
country: United States
facility: Research Site
state: Louisiana
city: Lafayette
country: United States
facility: Research Site
state: Louisiana
city: Mandeville
country: United States
facility: Research Site
state: Louisiana
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Bangor
country: United States
facility: Research Site
state: Maine
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Bowie
country: United States
facility: Research Site
state: Maryland
city: Columbia
country: United States
facility: Research Site
state: Maryland
city: Nottingham
country: United States
facility: Research Site
state: Maryland
city: Dearborn
country: United States
facility: Research Site
state: Michigan
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Midland
country: United States
facility: Research Site
state: Michigan
city: Traverse City
country: United States
facility: Research Site
state: Michigan
city: Ypsilanti
country: United States
facility: Research Site
state: Michigan
city: Coon Rapids
country: United States
facility: Research Site
state: Minnesota
city: Duluth
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Saint Cloud
country: United States
facility: Research Site
state: Minnesota
city: Tupelo
country: United States
facility: Research Site
state: Mississippi
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Springfield
country: United States
facility: Research Site
state: Missouri
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Bridgewater
country: United States
facility: Research Site
state: New Jersey
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Pomona
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Albany
country: United States
facility: Research Site
state: New York
city: Johnson City
country: United States
facility: Research Site
state: New York
city: Poughkeepsie
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Pinehurst
country: United States
facility: Research Site
state: North Carolina
city: Rocky Mount
country: United States
facility: Research Site
state: North Carolina
city: Sanford
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Springfield
country: United States
facility: Research Site
state: Ohio
city: Toledo
country: United States
facility: Research Site
state: Ohio
city: Allentown
country: United States
facility: Research Site
state: Pennsylvania
city: Chambersburg
country: United States
facility: Research Site
state: Pennsylvania
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: West Reading
country: United States
facility: Research Site
state: Pennsylvania
city: Wyomissing
country: United States
facility: Research Site
state: Pennsylvania
city: Rock Hill
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: Greeneville
country: United States
facility: Research Site
state: Tennessee
city: Jefferson City
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Oak Ridge
country: United States
facility: Research Site
state: Tennessee
city: Powell
country: United States
facility: Research Site
state: Tennessee
city: Amarillo
country: United States
facility: Research Site
state: Texas
city: Beaumont
country: United States
facility: Research Site
state: Texas
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Cypress
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Kingwood
country: United States
facility: Research Site
state: Texas
city: McKinney
country: United States
facility: Research Site
state: Texas
city: Mesquite
country: United States
facility: Research Site
state: Texas
city: Port Arthur
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Victoria
country: United States
facility: Research Site
state: Texas
city: Waco
country: United States
facility: Research Site
state: Texas
city: Newport News
country: United States
facility: Research Site
state: Virginia
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Winchester
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Abbotsford
country: Canada
facility: Research Site
state: British Columbia
city: Burnaby
country: Canada
facility: Research Site
state: British Columbia
city: Kamloops
country: Canada
facility: Research Site
state: British Columbia
city: North Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Victoria
country: Canada
facility: Research Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Moncton
country: Canada
facility: Research Site
state: New Brunswick
city: Moncton
country: Canada
facility: Research Site
state: New Brunswick
city: Saint John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Cambridge
country: Canada
facility: Research Site
state: Ontario
city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Scarborough
country: Canada
facility: Research Site
state: Ontario
city: Scarborough
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec City
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Granby
country: Canada
facility: Research Site
state: Quebec
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Laval
country: Canada
facility: Research Site
state: Quebec
city: Lévis
country: Canada
facility: Research Site
state: Quebec
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Québec
country: Canada
facility: Research Site
state: Quebec
city: Québec
country: Canada
facility: Research Site
state: Quebec
city: Rimouski
country: Canada
facility: Research Site
state: Quebec
city: Saint Charles Borromee
country: Canada
facility: Research Site
state: Quebec
city: Saint-Jérôme
country: Canada
facility: Research Site
state: Quebec
city: St-Hubert
country: Canada
facility: Research Site
state: Quebec
city: Terrebonne
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
city: Caguas
country: Puerto Rico
facility: Research Site
city: Carolina
country: Puerto Rico
facility: Research Site
Study officials:
affiliation: DalCor
name: David Kallend, MBBS
role: STUDY_DIRECTOR
References: