Efficacy and Safety Evaluation of Ninerafaxstat in Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Trial

Trial ID: 2024-515125-28-00
Protocol: IMB101-010
Sponsor: Imbria Pharmaceuticals Inc.

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Diseases & Conditions

Hypertrophic cardiomyopathy Cardiomyopathy

Objectives

The primary objective of this study is to evaluate the effect of ninerafaxstat on health status in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (5). The secondary objectives include:

Evaluation of ventilatory efficiency during exercise;
Assessment of patient-reported symptom frequency and severity;
Measurement of patient-reported physical limitation;
Analysis of health-related quality of life and overall health status;
Evaluation of exercise capacity.

The study also includes assessments regarding safety (4).

Participants

This study involves a total of 80 participants diagnosed with symptomatic non-obstructive hypertrophic cardiomyopathy. The study population includes both male and female individuals within the specified age ranges. Participants must be at least 18 years of age at the time of signing informed consent. Selection is based on a clinical diagnosis of hypertrophic cardiomyopathy consistent with current guideline definitions, characterized by unexplained left ventricular hypertrophy in the absence of other causative cardiac or systemic diseases. Additionally, subjects must possess adequate acoustic windows for echocardiography.

Plans and Procedures

This Phase 2b, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of ninerafaxstat in patients diagnosed with symptomatic non-obstructive hypertrophic cardiomyopathy. Participants will be assigned to receive either a 400 mg oral dose of ninerafaxstat in a modified-release tablet form or a placebo consisting of an identical-appearing tablet. The study protocol begins with a screening visit to confirm eligibility based on echocardiography findings and a clinical diagnosis of left ventricular hypertrophy. The primary objective is to assess changes from baseline to Week 12 in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. Secondary endpoints include assessments of ventilatory efficiency and exercise duration during cardiopulmonary exercise testing. The trial duration and participant involvement are structured around specific study visits, including follow-up assessments and an end-of-study visit.

Treatment

The experimental treatment consists of ninerafaxstat trihydrochloride monohydrate administered as a 400 mg modified-release tablet. This medication is intended for oral administration.

The control group receives a placebo, which is a tablet identical in appearance to the ninerafaxstat tablets.

Efficacy

The primary efficacy endpoint is the change from baseline to Week 12 in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Secondary endpoints include changes from baseline to Week 12 in the following parameters: KCCQ-TSS, KCCQ-PLS, and KCCQ-OSS. Additionally, changes from baseline to Week 12 in ventilatory efficiency, measured via the VE/VCO2 slope during cardiopulmonary exercise testing (CPET), and changes in exercise duration during CPET will be evaluated.

Inclusion and Exclusion Criteria

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Inclusion Criteria

All inclusion criteria can be found in the protocol (Section 5.1). 1. Informed Consent: Able to comprehend and willing to sign an informed consent form (ICF), and willing to comply with all trial procedures and restrictions for the duration specified in the Schedule of Events. Understands the risks involved.
Age: Individual ≥18 years of age at the time of signing informed consent.
Echocardiography: Has adequate acoustic windows for echocardiography.
Clinical Diagnosis: Has a clinical diagnosis of hypertrophic cardiomyopathy (HCM) consistent with current American College of Cardiology/American Heart Association and European Society of Cardiology Guideline definition, with unexplained left ventricular hypertrophy (LVH) in the absence of other cardiac or systemic diseases that can produce the magnitude of hypertrophy observed.

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Exclusion Criteria

All exclusion criteria can be found in the protocol (Section 5.2). 1. Informed Consent: Inability or unwillingness to provide informed consent or comply with trial procedures.
Cardiovascular Conditions: • History of obstructive hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract (LVOT) gradient ≥30 mmHg at rest or with provocation. • History of major adverse cardiovascular events (MACE) within 6 months prior to screening, including myocardial infarction, stroke, or cardiac surgery.
Medical Conditions: • Significant comorbidities that may impact the ability to complete the trial or the interpretation of results, such as uncontrolled diabetes, severe renal impairment, or active infection. • Known history of hepatitis B or C infection, or HIV infection.
Medications: • Use of disallowed medications that may interfere with the trial, such as other investigational drugs within 30 days prior to screening. • Requirement for treatment with drugs that may affect the study outcomes, such as certain antiarrhythmic or antihypertensive medications.
Substance Abuse: History of alcohol or substance abuse within the past year.
Pregnancy and Lactation: • Pregnant or breastfeeding women. • Women of childbearing potential not willing to use effective contraception during the study and for a specified period after the last dose.
Other Exclusions: • Participation in another clinical trial within 30 days prior to screening. • Any condition that, in the opinion of the investigator, would make participation in the trial unsafe or otherwise not in the best interest of the participant.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Recruiting	01 Feb 2026	3
Belgium	Recruiting	01 Feb 2026	3
France	Recruiting	01 Feb 2026	15
Germany	Recruiting	01 Feb 2026	12
Italy	Recruiting	01 Feb 2026	18
The Netherlands	Recruiting	01 Feb 2026	—
Poland	Recruiting	01 Feb 2026	10
Portugal	Recruiting	01 Feb 2026	12
Spain	Recruiting	01 Feb 2026	45
Netherlands	—	—	12