A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)

Study Overview
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Brief Summary
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The objective of the CAPACITY-HFpEF study is to evaluate the safety and efficacy of IW-1973 compared with placebo when administered daily for approximately 12 weeks to patients with HFpEF. The study will evaluate the effect of oral IW-1973 on peak exercise capacity in patients with HFpEF, with or without permanent or persistent atrial fibrillation.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Safety and Efficacy of Different Doses of IW-1973 Over 12 Weeks in Patients With Heart Failure With Preserved Ejection Fraction

Conditions
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Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Drug: IW-1973
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is an ambulatory male or female ≥45 years old at the Screening Visit Patient has heart failure with ejection fraction (EF) of ≥40% Patient has a peak VO2 measuring <80% of age- and sex-adjusted normal values Patient has evidence in medical history supporting clinical heart failure syndrome consisting of at least 1 of the following: Hospitalization or emergency department visit for heart failure within the past year Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) within the past 6 months Echocardiographic evidence within the past 12 months of at least 2 of the following: left ventricular (LV) hypertrophy, left atrial (LA) enlargement, or diastolic dysfunction Hemodynamic evidence of elevated filling pressures Patient meets at least 2 of the following criteria at the Screening Visit: Diagnosis of type 2 diabetes mellitus or prediabetes History of hypertension Body mass index (BMI) >30 kg/m2 Age ≥70 years Exclusion Criteria: Patient has had acute coronary syndrome or percutaneous coronary intervention within 30 days before Randomization Patient has had cardiac transplantation or has cardiac transplantation planned during the study Patient has had cardiac artery bypass graft, cardiac mechanical support implantation, or other cardiac surgery in the 3 months before the Screening Visit or planned during the study Patient has severe chronic obstructive coronary disease as defined by chronic oxygen dependence Patient had had heart failure hospitalization with discharge within 30 days before the Screening Visit Patient has a history of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products Patient has previously received IW-1973 in a study, or received an investigational drug during the 30 days or 5 half lives of that investigational drug (whichever is longer) before the Screening Visit, or is planning to receive another investigational drug at any time during the study Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of PDE5, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors in any form Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug Other exclusion criteria per protocol

Ages Eligible for Study
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Minimum Age: 45 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: IW-1973 High Dose<br> | Drug: IW-1973<br>* Oral Tablet<br>|
| Placebo Comparator: Placebo<br>Placebo to match experimental drug | Drug: Placebo Oral Tablet<br>* Oral Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented. | Day 1 up to Day 113 | 
| Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12 | Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12 | 6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate. | Baseline and Week 12 | 
| Change From Baseline in Ventilatory Efficiency at Week 12 | Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate. | Baseline and Week 12 | 
| CPET Responders at Week 12 | CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. | At Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Cardiovascular, HF, HFpEF