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NCT07001800PHASE2, PHASE3Recruiting

Ataciguat for Slowing the Progression of Moderate Calcific Aortic Valve Stenosis: A Randomized, Placebo Controlled Study

Kardigan, Inc.

Start Date

6/27/2025

Completion Date

9/30/2030

Summary

The purpose of this study is to evaluate if ataciguat slows the progression of moderate calcific aortic valve stenosis in adults.

Detailed Description

This study will be conducted in two parts: Part A and Part B. The purpose of Part A is to investigate whether ataciguat slows the progression of aortic valve calcium (AVC) deposition in adults with moderate calcific aortic valve stenosis (CAVS). The safety, tolerability, and pharmacokinetics of ataciguat will also be evaluated. Approximately 132 participants will be enrolled in Part A. Enrollment in Part B will begin once enrollment in Part A is complete. The purpose of Part B is to investigate whether ataciguat slows the rate of aortic valve area (AVA) loss and to evaluate the effect of ataciguat on peak oxygen consumption (VO2) in participants with moderate CAVS. The safety and tolerability of ataciguat will also be evaluated. Approximately 1144 participants will be enrolled in Part B.

Eligibility Criteria

Age Range: 50 years to No maximum

Key Inclusion Criteria: 1. Adult male or female at least 50 years of age 2. Has moderate CAVS as defined by: 1. An AVA of ≥1.0 cm2 to ≤1.50 cm2 2. An AVC score between \>300 to 1200 Agatston units (AU) for women and between \>300 to 2000 AU for men 3. Has a left ventricular ejection fraction (EF) of ≥45% at the time of Screening as determined by the echocardiography Imaging Core Laboratory 4. For participants in CPET sub-study in Part A and all participants in Part B: If on beta blockade, the dose must be stable for at least 90 days prior to the Screening Visit with no anticipated changes during the study Key Exclusion Criteria: 1. For participants in the CPET sub-study in Part A and all participants in Part B: Has any medical or physical condition that, in the Investigator's opinion, could lead to an inability to complete Protocol-required CPET procedures (eg, pulmonary disease, joint, leg, hip, back conditions that limit physical activity, or other absolute contraindications for CPET) 2. Anticipated or planned prior aortic valve replacement, repair, surgery, or intervention in the next 6 months 3. Has moderate, moderate-to-severe, or severe (Grade 2 or higher) mitral stenosis, mitral regurgitation, and/or aortic regurgitation 4. Has suspected or known congenital aortic valve disease including bicuspid aortic valve 5. New York Heart Association (NYHA) Class IV heart failure symptoms and/or requires continuous inotropes 6. Has history of hypertrophic, genetic/familial cardiomyopathy or cardiomyopathy related to amyloid or sarcoid 7. Has untreated obstructive coronary artery disease or anticipating coronary stenting surgery 8. Abnormal electrocardiogram (ECG) results or long-standing persistent or permanent atrial fibrillation

Interventions

DRUG

Ataciguat

DRUG

Placebo

Interested in This Trial?

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Conditions

Moderate Aortic Valve Stenosis

Locations

University of Alabama at Birmingham (UAB) - Medical Center

Birmingham, Alabama 35233

United States

Heart Center Research LLC

Huntsville, Alabama 35801

United States

Mayo Clinic - Phoenix

Phoenix, Arizona 85259

United States

National Heart Institute

Beverly Hills, California 90211

United States

UCLA Ronald Reagan Medical Center

Los Angeles, California 90095

United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California 92663

United States

Profound Research LLC at Southern California Heart Specialists

Pasadena, California 91105

United States

University of California, San Francisco (UCSF) - Medical Center

San Francisco, California 94143

United States

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center

Torrance, California 90502

United States

HCA Florida - JFK Hospital

Atlantis, Florida 33462

United States

New Generation of Medical Research

Hialeah, Florida 33016

United States

Memorial Healthcare System

Hollywood, Florida 33021

United States

Jacksonville Center for Clinical Research

Jacksonville, Florida 32216

United States

University of Miami

Miami, Florida 33136

United States

New Generation of Medical Research - Naples

Naples, Florida 34116

United States

Flourish Research - St. Augustine

Saint Augustine, Florida 32086

United States

Sarasota Memorial Hospital

Sarasota, Florida 34239

United States

University of South Florida

Tampa, Florida 33606

United States

Wellstar Kennestone Hospital

Marietta, Georgia 30060

United States

Northwestern University The Feinberg School of Medicine

Chicago, Illinois 60611

United States

Ascension Heart and Vascular/Alexian Brothers Heart & Vascular Institute

Elk Grove Village, Illinois 60007

United States

NorthShore University Health System

Glenview, Illinois 60026

United States

Riverside Medical Center - Illinois

Kankakee, Illinois 60901

United States

Cardiovascular Medicine

Moline, Illinois 61265

United States

Midwest Cardiovascular Institute

Naperville, Illinois 60540

United States

Methodist Medical Center of Illinois

Peoria, Illinois 61636

United States

Midwest Cardiovascular Research and Education Foundation

Elkhart, Indiana 46514

United States

The Heart Hospital at Deaconess Gateway

Newburgh, Indiana 47630

United States

University of Louisville Health

Louisville, Kentucky 40202

United States

University of Maryland Medical Center

Baltimore, Maryland 21201

United States

Johns Hopkins University School of Medicine

Baltimore, Maryland 21287

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Corewell Health

Royal Oak, Michigan 48073

United States

Henry Ford Hospital

West Bloomfield, Michigan 48322

United States

M Health Fairview St. John's Hospital

Maplewood, Minnesota 55109

United States

Mayo Clinic - Rochester

Rochester, Minnesota 55905

United States

Washington University

St Louis, Missouri 63110

United States

Missouri Baptist Medical Center

St Louis, Missouri 63131

United States

Deborah Heart and Lung Center

Browns Mills, New Jersey 08015

United States

Virtua Our Lady of Lourdes Hospital

Camden, New Jersey 08103

United States

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey 85831

United States

Inspira Medical Centers

Mullica Hill, New Jersey 08062

United States

Inspira Medical Center of Vineland

Vineland, New Jersey 08302

United States

Albany Medical Center

Albany, New York 12208

United States

University of Buffalo

Buffalo, New York 14203

United States

Montefiore Medical Center

The Bronx, New York 10467

United States

Duke University School of Medicine

Durham, North Carolina 27710

United States

Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health

Greensboro, North Carolina 27401

United States

Sanford Fargo

Fargo, North Dakota 58122

United States

The Lindner Center for Research and Education at The Christ Hospital

Cincinnati, Ohio 45219

United States

Bethesda North Hospital, TriHealth, Inc

Cincinnati, Ohio 45242

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

ProMedica Toledo Hospital

Toledo, Ohio 43606

United States

Ascension St. John Hospital

Tulsa, Oklahoma 74104

United States

Providence St. Vincent Medical Center

Portland, Oregon 97225

United States

Penn Medicine Lancaster General Hospital

Lancaster, Pennsylvania 17602

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania 15213

United States

OnSite Clinical Solutions, LLC - Rock Hill

Rock Hill, South Carolina 29732

United States

TriStar Centennial Medical Center

Nashville, Tennessee 37203

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

St. David's Heart and Vascular dba Austin Heart - Main Office

Austin, Texas 78705

United States

Methodist Dallas Medical Center

Dallas, Texas 75203

United States

Houston Methodist Hospital

Houston, Texas 77030

United States

University of Texas Medical Branch - Galveston

Houston, Texas 77555

United States

Baylor Scott and White - The Heart Hospital Baylor Plano

Plano, Texas 75093

United States

Methodist Hospital - San Antonio

San Antonio, Texas 78229

United States

Houston Methodist Sugar Land Hospital

Sugar Land, Texas 77479

United States

University of Utah Hospital & Clinics

Salt Lake City, Utah 84112

United States

St. Boniface Hospital

Winnipeg, Mantioba R2H 2A6

Canada

Montreal Heart Institute - Institut de Cardiologie de Montreal

Montreal, Quebec H1T 1C8

Canada

Centre Hospitalier de l Universite de Montreal (CHUM)

Montreal, Quebec H2X 0C1

Canada

Institut Universitaire de Cardiologie et de Pneumologie De Quebec

Québec, Quebec GIV 4G5

Canada