Clinical trial NCT07001800: A Study to Investigate Ataciguat for Slowing the Progression of Moderate Calcific Aortic Valve Stenosis
Official title: A Phase 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 type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Moderate Aortic Valve Stenosis
Keywords: Ataciguat
sGC activator
sGC stimulator
Aortic valve stenosis
Moderate aortic valve stenosis
Calcific aortic valve stenosis
CAVS
Moderate Calcific Aortic Valve Stenosis
Aortic Stenosis (AS)
Lead sponsor: Kardigan, Inc.
Sponsor class: INDUSTRY
First posted: 2025-06-03
Enrollment: 1410
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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

Primary outcomes:
measure: (Part A) Change in Aortic Valve Calcium (AVC) from baseline to Week 24.
timeFrame: Week 24
measure: (Part B Dual-Primary) Percent change in AVA as measured by echocardiogram from baseline to Week 48
timeFrame: Week 48
measure: (Part B Dual-Primary) Change in peak VO2 from baseline to Week 48
timeFrame: Week 48
Secondary outcomes:
measure: (Part A) Correlation in the change in AVC and the change in peak VO2 at Week 48
timeFrame: Week 48
measure: (Part A) Change in Peak VO2 from baseline to Week 48
timeFrame: Week 48
measure: (Part A) Change in Left Ventricular Mass Index (LVMI) from baseline to Week 48 as measured by echocardiogram.
timeFrame: Week 48
measure: (Part A) Change in Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) from baseline to Week 48.
timeFrame: Week 48
measure: (Part B) Change in Aortic Valve Calcium (AVC) from baseline to Week 48.
timeFrame: Week 48
measure: (Part B) Time to decision to proceed with TAVR/SAVR or all-cause death
timeFrame: Week 158
measure: (Part B) Percentage of participants with progression to AVA <1.0cm2 at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
Study officials:
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