Effects of NNC0537-1482 in people with heart failure

A Randomised, Placebo-controlled, Double-blinded Phase 1b Study Investigating Safety, Tolerability, Pharmacokinetics and Effects on Biomarkers From Multiple Ascending Doses of NNC0537-1482 in Participants With Heart Failure

This trial will test whether the new drug NNC0537-1482 is safe and how it works in adults aged 40-75 with symptomatic heart failure.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 40 Years to 75 Years
• Sex: All
• Sponsor: Novo Nordisk A/S (industry)
• Locations: 1 site (London)
• Trial ID: NCT07218627 on ClinicalTrials.gov

What this trial studies

This Phase 1, randomized, placebo-controlled trial is testing the safety and pharmacology of NNC0537-1482 in adults with symptomatic heart failure (NYHA class II–III), including HFmrEF and HFpEF. Participants are randomly assigned to receive NNC0537-1482 or placebo and will be monitored for up to 64 days after dosing, following a screening period of up to 28 days. Key inclusion criteria include age 40-75, BMI 18.5 to <40 kg/m^2, non-childbearing potential, and stable standard-of-care heart-failure medications. The study is sponsored by Novo Nordisk and conducted at Richmond Pharmacology in London with scheduled safety and clinical assessments.

Who should consider this trial

Good fit: Ideal candidates are adults 40-75 years old with symptomatic NYHA class II–III heart failure (HFmrEF or HFpEF), BMI 18.5–<40 kg/m^2, not of childbearing potential, and on stable heart-failure medications.

Not a fit: Patients with severe or unstable heart failure (for example NYHA class IV), those of childbearing potential, people outside the age or BMI ranges, or those with recent changes to heart-failure medications are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, NNC0537-1482 could become a new treatment option that is safe and improves symptoms or heart function for people with certain types of heart failure.

How similar studies have performed: This is an early-phase test of a novel compound with limited prior clinical data, so similar approaches in humans remain largely unproven.

Eligibility criteria

Inclusion Criteria:

* Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
* Male or females of non-childbearing potential.
* Age 40-75 years (both inclusive) at the time of signing the informed consent.
* Body Mass Index (BMI) range 18.5 - less than (\<) 40 kilogram per square meter (kg/m\^2).
* Symptomatic heart failure (New York Heart Association class II-III).
* Stable standard of care medical therapy for heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction (HFmrEF/HFpEF) defined by:
* No addition or removal of sodium-glucose cotransporter 2 inhibitors (SGLT2i), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs,) calcium-channel blockers or aldosterone antagonists, and no substantial change in dosage (greater than or equal to (≥)100% increase/decrease) at least 4 weeks before screening.
* On a diuretic therapy at least 2 weeks before screening without substantial change in dosing (≥50% increase/decrease), and on a stable diuretic therapy at least 1 week before screening.
* On the stable doses (not in titration period) of standard medical therapy for other comorbidities
* No hospitalizations due to heart failure (HF) between screening (V1) and randomisation (V2) confirmed at randomisation.
* Left ventricle ejection fraction (LVEF) greater than (\>) 40 percentage (%) documented by echocardiography at screening, or within 12 months prior to screening with no change in clinical status suggesting potential for deterioration in systolic function.

AND at least one of the following:

* N-terminal pro type-B natriuretic peptide (NT-proBNP) ≥125 picogram per milliliter (pg/mL) (for participants with sinus rhythm) or NT-proBNP ≥375 pg/mL (for participants with persistent/permanent atrial fibrillation) at screening, and ≥1 of the following (documented by echocardiography within 12 months prior to or at screening):
* Septal é \<7 or lateral \<10 or average E/é ≥10
* Pulmonary artery (PA) systolic pressure \>35 millimeters of mercury (mmHg)
* Left atrium (LA) enlargement, (width ≥3.8 centimeter (cm) or length ≥5.0 cm or area ≥20.0 square centimeter (cm\^2) or volume ≥55 milliliter (mL) or left atrial volume index (LAVI) ≥29 milliliter per square meter (mL/m\^2)
* Left ventricular hypertrophy (LVH) with septal thickness or posterior wall thickness ≥1.2 cm.
* Hospitalization with a primary diagnosis of decompensated HF requiring intravenous loop diuretic treatment within previous 12 months, and ≥2 of the following (documented by echocardiography within 12 months prior to or at screening):
* Septal é \<7 or lateral \<10 or average E/é ≥10
* PA systolic pressure \>35 mmHg
* LA enlargement, (width ≥3.8 cm or length ≥5.0 cm or area ≥20.0 cm\^2 or volume ≥55 mL or LAVI ≥29 mL/m\^2)
* LVH with septal thickness or posterior wall thickness ≥1.2 cm
* Ongoing use of diuretic therapy for ≥30 days before screening.
* Mean pulmonary capillary wedge pressure (PWP) ≥15 mmHg or left ventricular end-diastolic pressure (LVEDP) ≥15 mmHg documented during catheterization at rest or PA diastolic pressure measured by implantable monitor ≥15 mmHg or PWP or LVEDP ≥25 mmHg documented during catheterization at exercise.

Exclusion Criteria:

* Any prior echo measurement of LVEF less than or equal to (≤) 40%, under stable conditions, within the past 36 months.
* Previous participation in this study (defined as being randomised).
* Ongoing treatment with a neprilysin inhibitor (including angiotensin receptor/neprilysin inhibitor treatment), phosphodiesterase-5 (PDE5) inhibitors or soluble guanylate cyclase (sGC) stimulators.
* Acute coronary syndrome (ACS) (including myocardial infarction (MI)), stroke, transient ischemic attack (TIA), carotid surgery or angioplasty, cardiac surgery, other major cardiovascular surgery, or urgent percutaneous coronary intervention within the 3 months prior to screening.
* Current acute decompensated HF requiring augmented therapy.
* Hospitalisation within the last 90 days prior to screening with HF as the primary cause.
* Known or suspected hypersensitivity to study intervention(s) or related products.
* Probable alternative diagnoses that in the opinion of the investigator could account for the participant's HF symptoms (i.e., dyspnoea, fatigue) such as significant pulmonary disease (including primary pulmonary hypertension, severe chronic obstructive pulmonary disease), anaemia, hypothyroidism or obesity.
* Systolic blood pressure outside the range of 110-160 mmHg at screening or randomisation.
* Heart rate outside the range of 40-110 beats per minute (bpm) at screening or randomisation.
* Orthostatic hypotension (defined as a decrease in systolic blood pressure ≥20 mmHg or a decrease in diastolic blood pressure ≥10 mmHg from a supine position to standing after 3 minutes, at screening or randomisation).
* Atrioventricular-block II or III, QRS \>120 milliseconds (ms), or QTcF interval \>450 ms for men and \>470 ms for women, or any other clinically significant abnormal electrocardiogram (ECG) results as judged by the investigator at screening or randomisation.
* Participant has pacemaker, or implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy (CRT) or left ventricular assist device (LVAD).
* Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate \>110 bpm at screening or at randomisation.
* Significant changes of prescription medicinal products (dose or frequency) or non-prescription drugs between screening and randomisation visits, per investigator's assessment.
* Blood donation, plasma donation or blood draw any of the circumstances below:
* 400 mL within the past 90 days prior to the day of screening
* 50 mL within the past 30 days prior to the day of screening.
* Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the 3 months after screening.
* Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥2 times upper limit of normal (ULN).
* Estimated glomerular filtration (eGFR) \<20 milliliter per minute per 1.73 square meter according to 2021 CKD-EPI equation.
* History or presence of any other disease (i.e., including malignancies) with a life expectancy of \<1 year at screening.
* Receiving insulin for the treatment of diabetes type 1 or diabetes type 2.
* Glycated haemoglobin (HbA1c) of \> 8.0% as measured at screening.

Where this trial is running

London

• Richmond Pharmacology — London, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Novo Nordisk

Conditions: Heart Failure