HJB647 safety and tolerability in people with heart failure and reduced ejection fraction.

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 Ejection Fraction

Phase 1 Interventional Novartis · NCT07465653

This trial will test two doses of the experimental drug HJB647 versus placebo to see if it's safe and tolerated in adults with stable heart failure and reduced or mildly reduced ejection fraction who are already on sacubitril/valsartan.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment12 (estimated)
Ages18 Years to 100 Years
SexAll
SponsorNovartis Industry-sponsored
Locations3 sites (Bradenton, Florida and 2 other locations)
Trial IDNCT07465653 on ClinicalTrials.gov

What this trial studies

This is a randomized, participant- and investigator-blinded, placebo-controlled crossover Phase 1 trial enrolling about 12 adults with chronic stable HFrEF or HFmrEF who are on stable sacubitril/valsartan therapy. Participants are randomized 1:1:1 to one of three three-day treatment sequences that include a low dose of HJB647, a high dose of HJB647, and placebo, with domiciling for close monitoring during dosing. The study collects safety, tolerability, and pharmacokinetic data, with an in-clinic follow-up on Day 7 and a safety call on Day 33. The primary goal is to characterize safety and drug levels rather than clinical efficacy.

Who should consider this trial

Good fit: Adults (≥18 years) with chronic stable NYHA class II–III heart failure, LVEF <50%, NT-proBNP above protocol thresholds, and on a stable sacubitril/valsartan dose of at least 49/51 mg twice daily for ≥4 weeks are the intended participants.

Not a fit: People with recent acute decompensated heart failure (within 3 months), systolic blood pressure <105 mmHg, recent major cardiovascular events or surgery within 6 months, significant valve disease, or those not taking sacubitril/valsartan are unlikely to benefit from or be eligible for this study.

Why it matters

Potential benefit: If HJB647 is safe and tolerated, it could move to later trials and potentially become an additional treatment option for patients with reduced ejection fraction.

How similar studies have performed: This is an early-phase, first controlled crossover test of HJB647 in this population; while drugs like sacubitril/valsartan have proven benefit, HJB647 itself is novel and unproven.

Eligibility criteria

Show full inclusion / exclusion criteria
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 \<45 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.

Where this trial is running

Bradenton, Florida and 2 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Heart Failure With Reduced Ejection FractionSacubitrilValsartanHeart failureCardiac FailureMyocardial FailureHeart failure with reduced ejection fraction
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.