A Safety and Tolerability Study of HJB647 in Heart Failure Participants With Reduced Ejection Fraction

This is a multi-center, randomized, participant- and investigator- blinded, placebo- controlled crossover study to investigate the safety, tolerability, and pharmacokinetics of HJB647 in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).

The study will consist of approximately 12 participants randomly assigned in a 1:1:1 ratio to one of three 3-day treatment sequences comprised of two doses of HJB647 and placebo. Dosing of the HJB647 and placebo is planned for 3 consecutive days. Participants will be domiciled during study drug administration period for close monitoring with a follow-up in-clinic visit on Day 7. A safety call will be performed on Day 33.

Inclusion criteria

Participants eligible for inclusion in this study must meet all of the following criteria:

• Men and women aged 18 years or older
• Stable NYHA functional class II-III
• LVEF <50%
• NT-proBNP ≥600 pg/ml if in sinus rhythm or ≥900 pg/ml if in atrial fibrillation at screening
• On stable standard of care therapy with sacubitril/valsartan with a dose of at least 49/51 mg BID for at least 4 weeks before screening.

Exclusion criteria

Participants will be deemed ineligible for inclusion if they meet any of the following exclusion criteria:

• Acute decompensated heart failure within 3 months prior to screening
• SBP <105 mmHg at screening or baseline.
• Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, PCI, or carotid angioplasty within the 6 months prior to screening
• Hemodynamically significant mitral and/or aortic valve disease, or any prior valve replacement, except mitral regurgitation secondary to LV dilation at screening
• eGFR <30 ml/min/1.73m2 at screening, as measured by the CKD-EPI formula
• BMI >40 kg/m2
• Strong CYP3A4 inhibitors or inducers, sGC activators (vericiguat), PDE5 inhibitors, and nitroglycerin products
• Women of childbearing potential

Further eligibility criteria might apply in alignment with the trial protocol.