Ataciguat for Aortic Valve Stenosis

(KATALYST-AV Trial)

Recruiting at 48 trial locations

Overseen By Kardigan Clinical Trial Information Team

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kardigan, Inc.

Disqualifiers: Heart failure, Coronary artery disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

1410 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug ataciguat can slow the progression of aortic valve stenosis, a condition where the heart valve narrows, hindering blood flow. Participants will receive either ataciguat or a placebo (a harmless pill with no effect) for comparison. The trial seeks adults with moderate aortic valve stenosis, a specific level of heart valve narrowing, who can still engage in activities like exercise. As a Phase 3 trial, this is the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ataciguat is likely to be safe for humans?

Research has shown that ataciguat is generally safe for people. Studies found that patients with calcific aortic valve stenosis, a narrowing of the heart valve, experienced few side effects when taking ataciguat. In one trial, ataciguat slowed the progression of this condition over six months. Other studies are examining its safety for people with mild to moderate valve issues. So far, results suggest that the treatment does not cause major problems for most patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aortic valve stenosis?

Most treatments for aortic valve stenosis, like valve replacement surgeries or balloon valvuloplasty, are invasive and come with significant recovery times. But Ataciguat is unique because it works by targeting a specific enzyme pathway to potentially reduce the calcification of the aortic valve, offering a non-surgical approach. Researchers are excited about this treatment because it could provide a less invasive option that directly addresses the underlying cause of the condition, rather than just managing symptoms or replacing the affected valve. This novel mechanism of action could lead to a breakthrough in treating aortic valve stenosis more effectively and with fewer risks.

What evidence suggests that ataciguat might be an effective treatment for aortic valve stenosis?

In this trial, participants will receive either ataciguat or a placebo. Studies have shown that ataciguat can slow the progression of aortic valve stenosis, a condition where the heart valve narrows due to calcium buildup. In a previous study, patients who took ataciguat for six months experienced slower valve calcification compared to those on a placebo. Ataciguat reactivates an enzyme in the heart that reduces calcium buildup in the valve. Early research also suggests that ataciguat might delay the need for surgery by maintaining valve flexibility longer. This suggests that ataciguat could be a promising option for managing aortic valve stenosis. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with moderate calcific aortic valve stenosis, which is a heart valve disease. Participants should not have other conditions that could interfere with the study or pose additional risks.

Inclusion Criteria

Can perform Cardiopulmonary Exercise Testing (CPET)

Has a left ventricular ejection fraction (EF) of ≥45% at the time of Screening as determined by the echocardiography Core Laboratory

I am 50 years old or older.

Exclusion Criteria

I have had surgery or a procedure on my aortic valve before.

I have an irregular heartbeat or long-term atrial fibrillation.

I have a heart condition like cardiomyopathy or congenital heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive ataciguat or placebo to investigate the effect on aortic valve calcium deposition and peak oxygen consumption

48 weeks

Treatment Part B

Evaluation of ataciguat's effect on peak VO2 and aortic valve area reduction

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ataciguat

Trial Overview The study aims to determine if ataciguat can slow down the worsening of moderate calcific aortic valve stenosis compared to a placebo. It's essentially testing whether this drug can help manage heart valve disease better than no treatment.

How Is the Trial Designed?

Group I: Ataciguat Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Kardigan, Inc.

Lead Sponsor

Trials

1

Recruited

700+

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.066523

Reactivation of Oxidized Soluble Guanylate Cyclase as a ... A phase II randomized, placebo-controlled trial showed that treatment with ataciguat for 6 months slowed progression of aortic valve ...

2. tctmd.com tctmd.com/news/ataciguat-shows-potential-curbing-progression-aortic-stenosis

Ataciguat Shows Potential for Curbing Progression of ... Ataciguat, a novel anthranilic acid derivative, may safely slow progression of valve calcification and potentially delay the need for intervention.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07001800

NCT07001800 | A Study to Investigate Ataciguat for ... The purpose of this study is to evaluate if ataciguat slows the progression of moderate calcific aortic valve stenosis in adults. Detailed Description. This ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39989354/

Reactivation of Oxidized Soluble Guanylate Cyclase as a ... In vitro, ataciguat increased sGC signaling and reduced BMP2 (bone morphogenetic protein 2) signaling in aortic valve interstitial cells. In mice with ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20146640

A Study Evaluating the Effects of Ataciguat (HMR1766) on ... The primary objective of the current study is to determine whether Ataciguat (HMR1766) slows progression of valve calcification in patients with moderate ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02049203

Safety of Ataciguat in Patients With Moderate Calcific Aortic ... The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20144066

Safety of Ataciguat in Patients with Moderate Calcific Aortic ... This study will determine whether Ataciguat (HMR1766) is well-tolerated in patients with mild to moderate calcific aortic valve stenosis.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8647810/

Evaluating Medical Therapy for Calcific Aortic Stenosis Preclinical studies demonstrate that ataciguat reduces aortic valve calcification and slows progression of valve dysfunction; early stage clinical studies ( ...