A Phase 2 Dose-Finding Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Reduced Ejection Fraction

Trial details

Who runs it

Cardurion Pharmaceuticals Inc.

Trial code

EU 2023-508736-62-00

Record updated

2025. június 11.

Original description

To evaluate the effect of the 2 highest doses (twice daily [BID]) of tovinontrine on N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks compared to placebo in adult patients with HFrEFRead full original descriptionShow less

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Finding Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Reduced Ejection Fraction

To evaluate the effect of the 2 highest doses (twice daily [BID]) of tovinontrine on N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks compared to placebo in adult patients with HFrEF

Inclusion: Is an adult male or female patient ≥18 years of age, or adult age as per country guidelines, at the time of Screening; Has a 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; 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 ≥1000 pg/mL at the time of Screening; Is on stable optimized doses of guideline-directed HF therapy, per Investigator’s clinical judgment; Has had no addition of new guideline-directed HF therapy (with the exception of diuretics) within the 3 months prior to the time of Screening or during the Screening Period and is on stable optimized doses of all HF therapies, including diuretics, for a minimum of 4 weeks prior to the time of Screening and during the Screening Period, with no planned changes after randomization; Other protocol-defined criteria apply.

Exclusion: Has elective interventions (eg, percutaneous coronary intervention, de novo device implantations, percutaneous structural heart disease interventions, or major cardiac or non-cardiac surgery) planned to occur during study participation or has undergone this elective procedure <12 weeks prior to Screening; Has had prior or planned orthotopic heart transplantation; Has known bleeding diathesis; Has any clinically significant abnormal findings on physical examination as judged by the Investigator (or designee), AND/OR vital signs recorded at Screening of the following: o Average systolic blood pressure after a triplicate recording of <90 mmHg or ≥180 mmHg; o Average diastolic blood pressure after a triplicate recording of ≥90 mmHg; or o Heart rate <45 or >90 beats per minute; 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 clinical suspicion of infiltrative cardiomyopathy (eg, amyloid, sarcoid), hypertrophic cardiomyopathy (obstructive or non-obstructive), or HF secondary to severe valvular disease, active myocarditis, active pericarditis, or clinically significant congenital heart disease; Has any of the following findings at Screening: o A clinically significant abnormal finding on ECG considered by the Investigator to pose a risk to the safety of the patient; AND/OR o A QTcF interval of >500 msec AND/OR o A family history of Long QT Syndrome AND/OR o Utilization of concomitant therapies known to increase the risk of torsade de pointes; Has documented EF ≥40% by TTE within 6 months of the time of Screening or during the Screening Period; Has the presence of or plan for mechanical circulatory support; Other protocol-defined criteria apply; 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, IV iron, or diuretics) or routinely scheduled ultrafiltration.

EU CTIS 2023-508736-62-00