A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF)

Cardurion Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Cardiovascular Diseases; Heart Failure With Reduced Ejection Fraction; Heart Failure; Heart Diseases

Treatments: Drug: Tovinontrine (CRD-750); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06215911

CRD-750-201

2023-508736-62 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and effectiveness of tovinontrine compared to placebo to lower NT-proBNP in patients with chronic heart failure with reduced ejection fraction.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is an adult male or female patient 18 years of age

• Has evidence in the medical history supporting a diagnosis of clinical HF syndrome, NYHA functional class II to III, with the duration of at least 6 months prior to the time of Screening. The HF syndrome is defined by documentation of 1 or more of the following:

  • At least 1 of the typical symptoms due to HF such as dyspnea and/or fatigue limiting exercise capacity;
  • At least 1 of the typical signs of HF such as peripheral edema, elevated jugular venous pressure, pulmonary crackles; or
  • Hospitalization, emergency department visit, or outpatient visit for HF requiring intravenous (IV) or subcutaneous (SQ) diuresis within the past 12 months.

• Has ejection fraction (EF) ≤ 40% by transthoracic echocardiogram (TTE) performed and interpreted locally at the time of Screening;

• Has NT-proBNP level ≥ 600 pg/mL at the time of Screening. Patients with atrial fibrillation or flutter at the time of Screening are required to have an NT-proBNP level of ≥ 1000 pg/mL at the time of Screening;

• Is on stable optimized doses of guideline-directed HF therapy, per Investigator's clinical judgement, for a minimum of 4 weeks prior to the time of Screening and during Screening, with no planned changes after randomization.

• Has had no addition of new guideline-directed HF therapy within the 3 months prior to the time of Screening or during the Screening Period;

Exclusion criteria

• Has a documented EF >40% by TTE within 6 months of the time of Screening or during the Screening Period;
• Has evidence of recent HF exacerbation defined by hospitalization or requirement for IV or SQ diuretics within 60 days of the time of Screening or during the Screening Period;
• Has a requirement for routine, scheduled outpatient IV infusions for HF (ie, inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration;
• Has elective interventions (eg, percutaneous coronary intervention, device implantations, percutaneous structural heart disease interventions, cardiac and non-cardiac surgery) planned to occur during involvement in this study;
• Has acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, or carotid angioplasty within 60 days of the time of Screening or during the Screening Period;
• Has had a prior or planned orthotopic heart transplantation;
• Has presence of or plan for mechanical circulatory support;

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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400 participants in 4 patient groups, including a placebo group

Tovinontrine (CRD-750) - low dose

Experimental group

Treatment:

Drug: Tovinontrine (CRD-750)

Tovinontrine (CRD-750) - medium dose

Experimental group

Treatment:

Drug: Tovinontrine (CRD-750)

Tovinontrine (CRD-750) - high dose

Experimental group

Treatment:

Drug: Tovinontrine (CRD-750)

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo