Ataciguat for Slowing the Progression of Moderate Calcific Aortic Valve Stenosis: A Randomized, Placebo Controlled Study (KATALYST-AV)

Kardigan, Inc.

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Moderate Aortic Valve Stenosis

Treatments: Drug: Placebo; Drug: Ataciguat

Study type: Interventional

Funder types: Industry

Identifiers

NCT07001800

ATA-301

Details and patient eligibility

About

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

Full 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.

Enrollment: 1,276 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 ≥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 Imaging Core Laboratory

4. For participants 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 III or Class IV
6. Has a primary etiology for heart failure other than aortic valve disease
7. Has coronary artery disease or anticipating coronary stenting surgery
8. Abnormal electrocardiogram (ECG) results or long-standing persistent or permanent atrial fibrillation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,276 participants in 2 patient groups, including a placebo group

Ataciguat

Experimental group

Treatment:

Drug: Ataciguat

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo