A Study to Investigate Ataciguat for Slowing the Progression of Moderate Calcific Aortic Valve Stenosis

Phase 3

Recruiting

• Conditions: Moderate Aortic Valve Stenosis
• Interventions: Drug: Ataciguat; Drug: Placebo

• Registration Number: NCT07001800
• Lead Sponsor: Kardigan, Inc.

Brief 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 and whether the change in AVC effects peak oxygen consumption (pVO2) in adults with moderate calcific aortic valve stenosis (CAVS). The safety, tolerability, and pharmacokinetics of ataciguat will also be evaluated. The purpose of Part B is to evaluate the effect of ataciguat on peak VO2 and to investigate whether ataciguat reduces the rate of aortic valve area (AVA) in participants with moderate CAVS. The safety and tolerability of ataciguat will also be evaluated.

Study Timeline

• Study First Submitted: 2025-05-13
• Study First Submitted QC: 2025-05-23
• Study First Posted: 2025-06-03
• Study Start: 2025-06-27
• Status Verified: 2025-07
• Last Update Submitted: 2025-09-04
• Last Update Posted: 2025-09-11
• Primary Completion: 2028-08-31
• Study Completion: 2030-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1410

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 cm2 to ≤1.50 cm2
   2. An AVC score between ≥600 to 1200 Agatston units (AU) for women and between ≥600 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 Core Laboratory

4. Can perform Cardiopulmonary Exercise Testing (CPET)

Key

Exclusion Criteria

1. Has had a prior aortic valve replacement, repair, surgery, or intervention
2. Has moderate, moderate-to-severe, or severe (Grade 2 or higher) mitral stenosis, mitral regurgitation, and/or aortic regurgitation
3. Has known congenital aortic valve disease including bicuspid aortic valve
4. New York Heart Association (NYHA) Class III or Class IV
5. Has heart failure such as cardiomyopathy, congenital heart disease, myocarditis
6. Has coronary artery disease or anticipating coronary stenting surgery
7. Abnormal electrocardiogram (ECG) results or long-standing persistent or permanent atrial fibrillation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ataciguat	Ataciguat	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
(Part B Dual-Primary) Change in peak VO2 from baseline to Week 48	Week 48
(Part A) Change in Aortic Valve Calcium (AVC) from baseline to Week 24	Week 24
(Part B Dual-Primary) Percent change in AVA as measured by echocardiogram from baseline to Week 48	Week 48

Secondary Outcome Measures

Name	Time	Method
(Part A) Change in Left Ventricular Mass Index (LVMI) from baseline to Week 48 as measured by echocardiogram	Week 48
(Part A) Change in Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) from baseline to Week 48	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.
(Part A) Correlation in the change in AVC and the change in peak VO2 at Week 48	Week 48
(Part A) Change in Peak VO2 from baseline to Week 48	Week 48
(Part B) Change in Aortic Valve Calcium (AVC) from baseline to Week 48	Week 48
(Part B) Time to decision to proceed with TAVR/SAVR or all-cause death	Week 158
(Part B) Percentage of participants with progression to AVA <1.0cm2 at Week 48	Week 48

Trial Locations

Locations (47)

University of Alabama at Birmingham (UAB) - Medical Center; 🇺🇸 Birmingham, Alabama, United States

Heart Center Research LLC; 🇺🇸 Huntsville, Alabama, United States

National Heart Institute; 🇺🇸 Beverly Hills, California, United States

Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

Profound Research LLC at Southern California Heart Specialists; 🇺🇸 Pasadena, California, United States

University of California, San Francisco (UCSF) - Medical Center; 🇺🇸 San Francisco, California, United States

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center; 🇺🇸 Torrance, California, United States

HCA Florida - JFK Hospital; 🇺🇸 Atlantis, Florida, United States

New Generation of Medical Research; 🇺🇸 Hialeah, Florida, United States

New Generation of Medical Research - Naples; 🇺🇸 Naples, Florida, United States

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