Moderate Aortic Valve Stenosis
Conditions
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)
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 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.
Interventions
DRUGAtaciguat
Ataciguat will be administrated daily for up to 156 weeks
DRUGPlacebo
Placebo will be administrated daily for up to 156 weeks
Sponsors
Kardigan, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion 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 ≥1.0 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| (Part A) Change in Aortic Valve Calcium (AVC) score as assessed by non-contrast CT from baseline to Week 24 | Week 24 |
| (Part B Dual-Primary) Percent change in Aortic Valve Area (AVA) as measured by echocardiogram from baseline to Week 48 | Week 48 |
| (Part B Dual-Primary) Change in peak VO2 by CPET from baseline to Week 48 | Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| (Part A) Correlation in the change in AVC as assessed by non-contrast CT and change in VO2 at Week 48 | Week 48 | — |
| (Part A) Change in VO2 from baseline to Week 48 | Week 48 | — |
| Change in left ventricular diastolic function as assessed by E/e' from baseline to Week 48 | Week 48 | — |
| (Part A) Change in Left Ventricular Mass Index (LVMI) from baseline to Week 48 | 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 B) Change in AVC score as assessed by non-contrast CT 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 | — |
Countries
Canada, United States
Contacts
CONTACTKardigan Clinical Trial Information Team
Outcome results
None listed