A Phase 2 Clinical Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Preserved Ejection Fractio
- Conditions
- chronic heart failureMedDRA version: 26.1Level: LLTClassification code: 10076396Term: Heart failure with preserved ejection fraction Class: 10007541Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- CTIS2023-508737-13-00
- Lead Sponsor
- Cardurion Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
Is an adult male or female patient 18 years of age or older, at the time of Screening, Has evidence in the medical history supporting a diagnosis of clinical heart failure (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% and left atrial enlargement by transthoracic echocardiogram (TTE) performed and interpreted locally at the time of Screening, Has NT-proBNP level =300 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 =500 pg/mL at the time of Screening, Is on stable optimized doses of guideline-directed HF therapy for a minimum of 4 weeks prior to the time of Screening, and during the Screening Period, with no planned changes after randomization, 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, Other protocol-defined criteria apply
Has documented EF =60% by TTE within 6 months of the time of Screening or during the Screening Period, Has known bleeding diathesis, 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, diuretics) or routinely scheduled ultrafiltration, 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: - Average systolic blood pressure after a triplicate recording of <90 mmHg or =180 mmHg; - Average diastolic blood pressure after a triplicate recording of >90 mmHg; or - Heart rate <45 or >90 beats per minute., Has elective interventions (eg, percutaneous coronary intervention, device implantation, 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 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 had prior or planned orthotopic heart transplantation, Has the presence of or plan for mechanical circulatory support
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of tovinontrine on N-terminal pro b-type natriuretic peptide (NT-proBNP) levels versus placebo at Week 12 in adult patients with HFpEF.;Secondary Objective: To evaluate the safety and tolerability of tovinontrine versus placebo in adult patients with HFpEF, To evaluate the effect of tovinontrine on urine and plasma cyclic guanosine monophosphate (cGMP) versus placebo at Week 12 in adult patients with HFpEF, To assess the effect of tovinontrine on b-type natriuretic peptide (BNP) compared to placebo at Week 12 in adult patients with HFpEF, To assess the effect of tovinontrine on urine and plasma cGMP to NT-proBNP ratio compared to placebo at Week 12 in adult patients with HFpEF, To assess the effect of tovinontrine on urine and plasma cGMP to BNP ratio compared to placebo at Week 12 in adult patients with HFpEF, Other protocol-defined objectives apply;Primary end point(s): The percent change from baseline (pre-dose on Day 1) in plasma NT-proBNP at Week 12.
- Secondary Outcome Measures
Name Time Method Secondary end point(s):The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP at Week 12;Secondary end point(s):The percent change from baseline (pre-dose on Day 1) in BNP at Week 12;Secondary end point(s):The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP to NT-proBNP ratio at Week 12;Secondary end point(s):The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP to BNP ratio at Week 12;Secondary end point(s):The change from baseline (pre-dose on Day 1) in the KCCQ-23-CSS, KCCQ-23-OSS, and 8 domains (physical limitation, symptom stability, symptom frequency, symptom burden, total symptom score, quality of life, self-efficacy, and social limitation) at Week 12;Secondary end point(s):The change from baseline (pre-dose on Day 1) of the proportion of patients with =5, 10, and 20-point improvement in the KCCQ-23-CSS at Week 12;Secondary end point(s):The post-baseline NYHA classification at Week 12