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 (POWER-HF)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Akros Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

29 Feb 2024 → ongoing

Decision date (initial)

2024-02-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Akros Pharma Inc.

External identifiers

EU CT number

2023-504835-42-00

ClinicalTrials.gov

NCT06017609

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy, Safety, Others

• To evaluate the efficacy of JTT-861 administered for 12 weeks in subjects with heart failure with reduced ejection fraction (HFrEF)
• To evaluate the safety and tolerability of JTT-861 administered for 12 weeks in subjects with HFrEF
• To evaluate the pharmacokinetics (PK) of JTT-861 administered for 12 weeks in subjects with HFrEF

Conditions and MedDRA coding

Heart Failure (Heart Failure with Reduced Ejection Fraction)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female, age 30-85 years (inclusive), at the Screening Visit;
2. Has a clinical diagnosis of symptomatic heart failure (HF) ≥90 days prior to the Screening Visit;
3. Is in New York Heart Association (NYHA) functional class II or III at the Screening Visit;
4. 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);
5. Has left ventricular ejection fraction (LVEF) ≤35% at the Screening Visit;
6. 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; Note: In the context of paced rhythm, the underlying cardiac rhythm should be considered when selecting the NT-pro-BNP cutoff level.

Exclusion criteria 6

1. Has a confirmed acute myocardial infarction (MI) (i.e., Type 1) or unstable angina within 90 days prior to the Screening Visit;
2. 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);
3. 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;
4. Has clinically significant congenital heart disease, active myocarditis or constrictive pericarditis;
5. Has current acute worsening HF requiring additional treatment with diuretics, vasodilators and/or inotropic medications at the Screening Visit;
6. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Efficacy Parameters • Change from baseline to end of treatment (EOT) in: o LVEF as assessed by two-dimensional echocardiography (2D-echo) o Left ventricular end-systolic volume (LVESV) index as assessed by 2D-echo o Left ventricular end-diastolic volume (LVEDV) index as assessed by 2D-echo
2. Efficacy Parameters • Change from baseline to end of treatment (EOT) in: o Left atrial volume (LAV) as assessed by 2D-echo o NT-pro-BNP o Kansas City Cardiomyopathy Questionnaire (KCCQ) scores
3. Pharmacokinetic (PK) Parameters • JTT-861 trough plasma concentrations at Weeks 4, 8 and 12 • JTT-861 plasma concentrations (post-dose) at Weeks 2, 4 and 8
4. Safety Parameters • Number of subjects with adverse events (AEs), change from baseline in safety laboratory, vital signs and 12-lead electrocardiogram (ECG) parameters.

Secondary endpoints 3

1. Exploratory Efficacy Parameters • Change from baseline to EOT in: o eGFR o Cystatin C o Urine albumin-to-creatinine ratio (ACR) o Hemoglobin A1c (HbA1c) and plasma glucose
2. Exploratory Efficacy Parameters • Change from baseline to EOT in: o Tricuspid annular plane systolic excursion (TAPSE) as assessed by 2D-echo o Fractional area change (FAC) as assessed by 2D-echo o Right ventricular (RV) longitudinal strain as assessed by 2D-echo o Tricuspid regurgitation peak gradient (TRPG) as assessed by 2D-echo
3. Exploratory Pharmacodynamic (PD) Parameters • Change from baseline to EOT in branched-chain amino acids (BCAAs: isoleucine, leucine and valine) and alanine plasma concentrations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Akros Pharma Inc.

Sponsor organisation

Akros Pharma Inc.

Address

302 Carnegie Center Suite 300

City

Princeton

Postcode

08540-6376

Country

United States

Scientific contact point

Organisation

Akros Pharma Inc.

Contact name

Osamu Yamada

Public contact point

Organisation

Akros Pharma Inc.

Contact name

Osamu Yamada

Third parties 8

Locations

5 EU/EEA countries · 59 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 102 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications