Evaluate Efficacy, Safety and Tolerability of JTT-861 in Subjects With Heart Failure With Reduced Ejection Fraction

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects with heart failure with reduced ejection fraction (HFrEF) who are on a stable, guideline-directed medical therapy for heart failure.

Official Title
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A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety and Tolerability of JTT-861 Administered for 12 Weeks in Subjects With Heart Failure With Reduced Ejection Fraction

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Drug: JTT-861 Capsules
* Drug: Placebo Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a clinical diagnosis of symptomatic heart failure (HF) ≥90 days prior to the Screening Visit; Is in New York Heart Association (NYHA) functional class II or III at the Screening Visit; Is on stable, guideline-directed therapy for HF, consistent with American Heart Association (AHA), American College of Cardiology (ACC), Heart Failure Society of America (HFSA) or European Society of Cardiology (ESC) guidelines for ≥4 weeks prior to the Screening Visit (with at least half of maximal labeled dose of renin-angiotensin-aldosterone system (RAAS) inhibitors and β-blockers, if tolerated); Has left ventricular ejection fraction (LVEF) ≤35% at the Screening Visit; Has a serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) level ≥600 pg/mL (or ≥900 pg/mL if the subject has atrial fibrillation or atrial flutter) at the Screening Visit. Exclusion Criteria: Has a confirmed acute myocardial infarction (MI) (i.e., Type 1) or unstable angina within 90 days prior to the Screening Visit; Has a history of coronary revascularization (percutaneous coronary intervention [PCI] and/or coronary artery bypass graft [CABG]) or other cardiovascular surgery within 90 days prior to the Screening Visit or planned cardiovascular surgery during the study through the Follow-up Visit); Has started cardiac resynchronization therapy (CRT) within 90 days prior to the Screening Visit or has planned CRT during the study through the Follow-up Visit; Has clinically significant congenital heart disease, active myocarditis or constrictive pericarditis; Has current acute decompensated HF requiring additional treatment with diuretics, vasodilators and/or inotropic medications at the Screening Visit; Has clinically significant chronic renal insufficiency (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation) at the Screening Visit.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 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: JTT-861 Dose 1<br>JTT-861 Capsules Dose 1 orally once daily for 12 weeks | Drug: JTT-861 Capsules<br>* Active drug capsules containing JTT-861<br>|
| Experimental: JTT-861 Dose 2<br>JTT-861 Capsules Dose 2 orally once daily for 12 weeks | Drug: JTT-861 Capsules<br>* Active drug capsules containing JTT-861<br>|
| Experimental: Placebo<br>Placebo Capsules orally once daily for 12 weeks | Drug: Placebo Capsules<br>* Placebo capsules matching in appearance to the active drug capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to end of treatment (EOT) in left ventricular ejection fraction (LVEF) as assessed by two-dimensional echocardiography (2D-echo) |  | 12 Weeks | 
| Change from baseline to EOT in left ventricular end-systolic volume (LVESV) index as assessed by 2D-echo |  | 12 Weeks | 
| Change from baseline to EOT in left ventricular end-diastolic volume (LVEDV) index as assessed by 2D-echo |  | 12 Weeks | 
| Change from baseline to EOT in left atrial volume (LAV) as assessed by 2D-echo |  | 12 Weeks | 
| Change from baseline to EOT in N-terminal pro b-type natriuretic peptide (NT-pro-BNP) |  | 12 Weeks | 
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores from baseline |  | 16 Weeks | 
| Number of subjects with treatment-emergent adverse events |  | Up to 16 Weeks | 
| Trough plasma concentrations of JTT-861 |  | Weeks 4, 8 and 12 | 
| Post-dose plasma concentrations of JTT-861 |  | Weeks 2, 4 and 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JTT-861, Efficacy, Safety, Tolerability, Chronic Heart Failure, HFrEF, Heart Failure