Cardiovascular Diseases, Heart Diseases, Heart Failure, Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
PDE9, PED9 Inhibitor, Heart Failure, CRD-750, Tovinontrine, HFrEF
Brief summary
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.
Interventions
Tablets administered orally
DRUGPlacebo
Tablets administered orally
Sponsors
Cardurion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in biomarkers from Baseline to Week 12 - NT-proBNP by treatment group | Baseline to Week 12 | The percent change in plasma NT-proBNP from Baseline to Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in biomarkers at Week 12 - NT-proBNP | Baseline to Week 12 | The percent change in plasma NT-proBNP will be calculated from Baseline to Week 12. The correlation of plasma concentration with percent change in plasma NT-proBNP will be evaluated. |
| Change in biomarkers at week 12 by treatment group - cGMP | Baseline to Week 12 | The percent change in urine and plasma cGMP from Baseline to Week 12. |
| Change in biomarkers at week 12 by treatment group - BNP | Baseline to Week 12 | The percent change in BNP from Baseline to Week 12. |
| Change in the biomarker ratio at Week 12 - NT-proBNP | Baseline to Week 12 | The percent change in the urine and plasma cGMP to NT-proBNP ratio at week 12 |
| Change in the biomarker ratio at Week 12 - BNP | Baseline to Week 12 | The percent change in the urine and plasma cGMP to BNP ratio from Baseline to Week 12 |
| The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23-Clinical Summary Score | Baseline to Week 12 | Scaled 0 to 100 where lower scores represent worse health status than higher scores |
| The change from baseline in the Kansas City Cardiomyopathy Questionnaire 23- Overall Summary Score | Baseline to Week 12 | Scaled 0 to 100 where lower scores represent worse health status than higher scores |
| The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23-CSS - Categorical | Week 12 | The proportion of patients with \>=5, 10 and 20-point improvement in the KCCQ-23-CSS. |
| Treatment Emergent Adverse Events (TEAEs) | Baseline to Week 12 | The number of participants with TEAEs including drug related AEs, serious AEs (SAEs), and AEs leading to study drug discontinuation. |
| New York Heart Association Classification | Week 12 | Class I to IV are possible with a higher classification representing worsening heart failure status. |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, Georgia, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, New Zealand, Poland, Slovakia, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORGail Berman
Senior VP Head, Clinical Development Cardurion
Outcome results
None listed