A Phase 2 Clinical Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Preserved Ejection Fraction
- Conditions
- chronic heart failure
- Interventions
- Drug: Placebo
- Registration Number
- 2023-508737-13-00
- Lead Sponsor
- Cardurion Pharmaceuticals Inc.
- Brief Summary
To evaluate the effect of tovinontrine on N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks compared to placebo in adult patients with HFpEF.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Not specified
- Target Recruitment
- 128
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 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, 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
Has documented EF ≥60% by TTE within 6 months of the time of Screening or during the Screening Period
Has had prior or planned orthotopic heart transplantation
Has the presence of or plan for mechanical circulatory support
Has any of the following findings at Screening: A clinically significant abnormal finding on electrocardiogram (ECG) considered by the Investigator to pose a risk to the safety of the patient; and/or oPersonal or family history of Long QT syndrome; and/or A QTcF interval of >500 msec; and/or oUtilization of concomitant therapies known to increase the risk of torsade de pointe
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, IV iron, or 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, 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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tovinontrine (CRD-750) Tovinontrine (CRD-750 - Placebo Placebo -
- Primary Outcome Measures
Name Time Method The percent change from baseline (pre-dose on Day 1) in plasma NT-proBNP at Week 12. The percent change from baseline (pre-dose on Day 1) in plasma NT-proBNP at Week 12.
- Secondary Outcome Measures
Name Time Method The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP at Week 12 The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP at Week 12
The percent change from baseline (pre-dose on Day 1) in BNP at Week 12 The percent change from baseline (pre-dose on Day 1) in BNP at Week 12
The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP to NT-proBNP ratio at Week 12 The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP to NT-proBNP ratio at Week 12
The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP to BNP ratio at Week 12 The percent change from baseline (pre-dose on Day 1) in urine and plasma cGMP to BNP ratio at Week 12
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 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
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 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
The post-baseline NYHA classification at Week 12 The post-baseline NYHA classification at Week 12
Related Research Topics
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Trial Locations
- Locations (50)
Edumed s.r.o.
🇨🇿Hradec Kralove, Czechia
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Prague, Czechia
Fakultni Nemocnice Brno
🇨🇿Brno, Czechia
Fakultni Nemocnice Hradec Kralove
🇨🇿Novy Hradec Kralove, Czechia
Centro Cardiologico Monzino S.p.A.
🇮🇹Milan, Italy
Humanitas Research Hospital
🇮🇹Rozzano, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
🇮🇹Bergamo, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Zentrum fuer klinische Studien Suedbrandenburg GmbH
🇩🇪Elsterwerda, Germany
Otto Von Guericke Universitaet Magdeburg
🇩🇪Magdeburg, Germany
Scroll for more (40 remaining)Edumed s.r.o.🇨🇿Hradec Kralove, CzechiaJiří VeselýSite contact+420731447001vesely.edumed@gmail.com