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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified April 2026 by Kardigan, Inc.
Sponsor
Kardigan, Inc.
Information Provided by (Responsible Party)
Kardigan, Inc.
Clinicaltrials.gov Identifier
NCT07001800
Other Study ID Numbers:
ATA-301
First Submitted
May 12, 2025
First Posted
June 2, 2025
Last Update Posted
May 5, 2026
Last Verified
April 2026

ClinicalTrials.gov processed this data on May 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Moderate Aortic Valve Stenosis
Drug: AtaciguatDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment1276 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Phase 2b/3, Randomized, Double-Blinded, Placebo Controlled Study ChecKing the Efficacy and Safety of ATAciguat to Slow the Progression of VaLvular DYsfunction in Participants With Moderate Calcific Aortic Valve STenosis
Study Start DateJune 26, 2025
Actual Primary Completion Date2yrs 1mo from now
Actual Study Completion Date4yrs 2mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Ataciguat
Drug: Ataciguat
Ataciguat will be administrated daily for up to 156 weeks
Placebo
Drug: Placebo
Placebo will be administrated daily for up to 156 weeks

Outcome Measures

Primary Outcome Measures
  1. (Part A) Change in Aortic Valve Calcium (AVC) score as assessed by non-contrast CT from baseline to Week 24
  2. (Part B Dual-Primary) Percent change in Aortic Valve Area (AVA) as measured by echocardiogram from baseline to Week 48
  3. (Part B Dual-Primary) Change in peak VO2 by CPET from baseline to Week 48
Secondary Outcome Measures
  1. (Part A) Correlation in the change in AVC as assessed by non-contrast CT and change in VO2 at Week 48
  2. (Part A) Change in VO2 from baseline to Week 48
  3. Change in left ventricular diastolic function as assessed by E/e' from baseline to Week 48
  4. (Part A) Change in Left Ventricular Mass Index (LVMI) from baseline to Week 48
  5. (Part A) Change in Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) from baseline to Week 48
    KCCQ-23 is a patient reported outcome instrument with minimum score = 0 and maximum score = 100 where higher score indicates better health status. There are no units to the score.
  6. (Part B) Change in AVC score as assessed by non-contrast CT from baseline to Week 48
  7. (Part B) Time to decision to proceed with TAVR/SAVR or all-cause death
  8. (Part B) Percentage of participants with progression to AVA <1.0cm2 at Week 48

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsKardigan, Inc.
Locations
University of Alabama at Birmingham (UAB) - Medical Center | Birmingham Alabama, United States, 35233Heart Center Research LLC | Huntsville Alabama, United States, 35801Onyx Clinical Research - Peoria | Peoria Arizona, United States, 85381Mayo Clinic - Phoenix | Phoenix Arizona, United States, 85259National Heart Institute | Beverly Hills California, United States, 90211UCLA Ronald Reagan Medical Center | Los Angeles California, United States, 90095Hoag Memorial Hospital Presbyterian | Newport Beach California, United States, 92663Profound Research LLC at Southern California Heart Specialists | Pasadena California, United States, 91105University of California, San Francisco (UCSF) - Medical Center | San Francisco California, United States, 94143Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center | Torrance California, United States, 90502HCA Florida - JFK Hospital | Atlantis Florida, United States, 33462New Generation of Medical Research | Hialeah Florida, United States, 33016Memorial Healthcare System | Hollywood Florida, United States, 33021Jacksonville Center for Clinical Research | Jacksonville Florida, United States, 32216University of Miami | Miami Florida, United States, 33136New Generation of Medical Research - Naples | Naples Florida, United States, 34116Flourish Research - St. Augustine | Saint Augustine Florida, United States, 32086Sarasota Memorial Hospital | Sarasota Florida, United States, 34239University of South Florida | Tampa Florida, United States, 33606Wellstar Kennestone Hospital | Marietta Georgia, United States, 30060Northwestern University The Feinberg School of Medicine | Chicago Illinois, United States, 60611Ascension Heart and Vascular/Alexian Brothers Heart & Vascular Institute | Elk Grove Village Illinois, United States, 60007NorthShore University Health System | Glenview Illinois, United States, 60026Riverside Medical Center - Illinois | Kankakee Illinois, United States, 60901Midwest Cardiovascular Institute | Naperville Illinois, United States, 60540Methodist Medical Center of Illinois | Peoria Illinois, United States, 61636Midwest Cardiovascular Research and Education Foundation | Elkhart Indiana, United States, 46514University of Louisville Health | Louisville Kentucky, United States, 40202University of Maryland Medical Center | Baltimore Maryland, United States, 21201Johns Hopkins University School of Medicine | Baltimore Maryland, United States, 21287Massachusetts General Hospital | Boston Massachusetts, United States, 02114Brigham and Women's Hospital | Boston Massachusetts, United States, 02115Corewell Health | Royal Oak Michigan, United States, 48073Henry Ford Hospital | West Bloomfield Michigan, United States, 48322M Health Fairview St. John's Hospital | Maplewood Minnesota, United States, 55109Mayo Clinic - Rochester | Rochester Minnesota, United States, 55905Washington University | St Louis Missouri, United States, 63110Deborah Heart and Lung Center | Browns Mills New Jersey, United States, 08015Virtua Our Lady of Lourdes Hospital | Camden New Jersey, United States, 08103Atlantic Health System - Morristown Medical Center | Morristown New Jersey, United States, 85831Inspira Medical Centers | Mullica Hill New Jersey, United States, 08062Inspira Medical Center of Vineland | Vineland New Jersey, United States, 08302Albany Medical Center | Albany New York, United States, 12208University of Buffalo | Buffalo New York, United States, 14203Montefiore Medical Center | The Bronx New York, United States, 10467Duke University School of Medicine | Durham North Carolina, United States, 27710Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health | Greensboro North Carolina, United States, 27401Sanford Fargo | Fargo North Dakota, United States, 58122The Lindner Center for Research and Education at The Christ Hospital | Cincinnati Ohio, United States, 45219Bethesda North Hospital, TriHealth, Inc | Cincinnati Ohio, United States, 45242Cleveland Clinic | Cleveland Ohio, United States, 44195ProMedica Toledo Hospital | Toledo Ohio, United States, 43606Ascension St. John Hospital | Tulsa Oklahoma, United States, 74104University of Pennsylvania | Philadelphia Pennsylvania, United States, 19104University of Pittsburgh Medical Center | Pittsburgh Pennsylvania, United States, 15213OnSite Clinical Solutions, LLC - Rock Hill | Rock Hill South Carolina, United States, 29732TriStar Centennial Medical Center | Nashville Tennessee, United States, 37203Vanderbilt University Medical Center | Nashville Tennessee, United States, 37232St. David's Heart and Vascular dba Austin Heart - Main Office | Austin Texas, United States, 78705Methodist Dallas Medical Center | Dallas Texas, United States, 75203Houston Methodist Hospital | Houston Texas, United States, 77030University of Texas Medical Branch - Galveston | Houston Texas, United States, 77555Baylor Scott and White - The Heart Hospital Baylor Plano | Plano Texas, United States, 75093Methodist Hospital - San Antonio | San Antonio Texas, United States, 78229Houston Methodist Sugar Land Hospital | Sugar Land Texas, United States, 77479University of Utah Hospital & Clinics | Salt Lake City Utah, United States, 84112St. Boniface Hospital | Winnipeg Mantioba, Canada, R2H 2A6Montreal Heart Institute - Institut de Cardiologie de Montreal | Montreal Quebec, Canada, H1T 1C8Centre Hospitalier de l Universite de Montreal (CHUM) | Montreal Quebec, Canada, H2X 0C1Institut Universitaire de Cardiologie et de Pneumologie De Quebec | Québec Quebec, Canada, GIV 4G5