Effectiveness of CRD-740 in Heart Failure

Study Overview
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Brief Summary
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This is a two-part study evaluating the effectiveness of CRD-740 in patients with either Heart Failure with Reduced Ejection Fraction (HFrEF) or Heart Failure with Preserved Ejection Fraction (HFpEF) after 12 weeks of treatment. The primary objective in Part A is to assess the effect of CRD-740 compared to placebo in plasma cGMP at Week 4. The primary objective in Part B is to determine whether CRD-740 reduces NT-proBNP compared to placebo at Week 12.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess the Effectiveness of CRD-740 in Subjects With Chronic Heart Failure (CARDINAL-HF)

Conditions
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Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure With Preserved Ejection Fraction, Cardiovascular Diseases, Heart Diseases

Intervention / Treatment
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* Drug: CRD-740
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or Females ≥18 years of age, at screening. Diagnosis of clinical heart failure syndrome, New York Heart Association functional class II - III for at least 6 months prior to screening For Part A: Ejection Fraction ≤40% by echocardiography at screening. NT-proBNP level ≥600 pg/ml at screening. Subjects with atrial fibrillation or flutter at screening are required to have an NT-proBNP level of ≥1000 pg/mL at screening. For Part B: For subjects with EF ≤40%: Ejection Fraction ≤40% by echocardiography at screening. NT-proBNP level ≥600 pg/ml at screening. Subjects with atrial fibrillation or flutter at screening are required to have an NT-proBNP level of ≥1000 pg/mL at screening. For subjects with EF >40%: EF >40% and left atrial enlargement by echocardiography at screening. NT-proBNP level ≥300 pg/ml at screening. Subjects with atrial fibrillation or flutter at screening are required to have an NT-proBNP level of ≥500 pg/mL at screening. Stable doses of guideline-directed heart failure therapy for a minimum of 4 weeks prior to screening that has been individually optimized according to standard practice guidelines and no addition of guideline-directed heart failure therapy within 3 months of screening. Exclusion Criteria: Documented EF≥60% within 6 months of screening. Recent HF exacerbation defined by hospitalization or requirement for intravenous diuretics within 60 days of screening. Subjects with planned interventions (e.g., percutaneous coronary intervention, devices) etc. occurring during their involvement in this study. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery or carotid angioplasty within 60 days of screening. Subjects with clinical suspicion of infiltrative cardiomyopathy (e.g., 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. Prior or planned orthotopic heart transplantation. Presence of or plan for mechanical circulatory support. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRD-740<br>Part A: Participants in Part A randomly assigned to this arm will take CRD-740 twice daily at two ascending dose levels over 12 weeks. Part B: Participants in Part B randomly assigned to this arm will take CRD-740 twice daily at a single dose level over 12 weeks. | Drug: CRD-740<br>* Tablets administered orally.<br>|
| Placebo Comparator: Placebo<br>Part A: Participants in Part A randomly assigned to this arm will take placebo twice daily at two ascending dose levels over 12 weeks. Part B: Participants in Part B randomly assigned to this arm will take placebo twice daily at a single dose level over 12 weeks. | Drug: Placebo<br>* Tablets administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: The change from baseline (Day -1) in plasma cGMP at Week 4. |  | Baseline to Week 4 | 
| Part B: The change from baseline (Day 1) in NT-proBNP at Week 12. |  | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: The change from baseline (Day 1) in plasma BNP at Week 12. |  | Baseline to Week 12 | 
| Part B: The change from baseline (Day 1) in plasma cGMP at Week 12. |  | Baseline to Week 12 | 
| Part B: The change from baseline (Day 1) in the KCCQ-23-CS at Week 12. |  | Baseline to Week 12 | 
| Part B: The proportion of subjects with ≥5-point improvement from baseline in the KCCQ-23- CS at Week 12. |  | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDE9, Heart Failure, CRD-740, HFpEF, HFrEF