HF-POLARIS

Not yet recruitingPhase 3

A Research Study to Look at How Well NNC0487-0111 Works Compared to Placebo in People With Heart Failure and Obesity

Efficacy and Safety of NNC0487-0111 Compared to Placebo on Morbidity and Mortality in People With Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity

Lead sponsor

Novo Nordisk A/S

Asset

Amycretin / zenagamtide

Oral · GLP-1 / amylin

Listed sites

825

Recruiting sites

—

Enrollment

5,610

estimated

Study population

Heart failure, Obesity / overweight

Key I/E criterion

—

Primary endpoints

•Expanded / custom MACE composite (Heart-failure hospitalization, Cardiovascular death)•Heart-failure composite (Heart-failure hospitalization, Urgent heart-failure visit)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07567001

Org study IDNN9490-8266

Secondary ID2025-523717-29European Medical Agency (EMA)

Secondary IDU1111-1328-2701World Health Organization (WHO)

Timeline

Milestones

Study first posted2026-05-05actual

Last update posted2026-05-05actual

Study start2026-05-11estimated

Primary completion2029-07-23estimated

Study completion2029-08-15estimated

Assets

Investigational agents

Amycretin / zenagamtide

Study populations

Who this study enrolls

Heart failureObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Body Mass Index (BMI) greater than or equal to (>=) 30 kilograms per square metre (kg/m^2) at screening.

•Diagnosis of HF with New York Heart Association (NYHA) class II-IV and in stable condition at screening, at the discretion of the investigator.

For participants with Type 2 Diabetes (T2D) at screening:

- Diagnosed with T2D >= 30 days before screening.

Exclusion criteria

•MI, stroke, unstable angina pectoris or worsening HF leading to either hospitalization or intravenous loop diuretics within 30 days prior to the day of screening and until randomization.

•HF due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, Chagas cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, or uncorrected primary valve disease of moderate or severe degree.

•Severe pulmonary disease including primary pulmonary hypertension, chronic pulmonary embolism, or severe chronic obstructive pulmonary disease (COPD) defined as:

•requiring home oxygen; or - ongoing oral corticosteroid therapy; or - hospital for COPD Exacerbation within 12 months prior to screening.

•Any other condition judged by the investigator to be the cause of HF symptoms (e.g., anaemia, hypothyroidism).

Glycaemia-related:

•History of type 1 diabetes.

•Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) within 180 days before screening or who, at the time of screening, are expected to require treatment within 180 days after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening or in the period between screening and randomization. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

•Glycated haemoglobin (HbA1c) greater than (>) 10 percent (%) (86 [millimoles per mole] mmol/mol) as measured by local or central laboratory at screening.

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Cardiovascular outcomes

Heart failure

Renal / kidney

Cardiovascular outcomes

3 endpoints

Primary/protocol endpoint

Time to first occurrence of a composite Heart Failure (HF) endpoint consisting of cardiovascular (CV) death

Time frame:From baseline (week 0) to 165 weeks

Expanded / custom MACE composite

time to event, event

componentsHeart-failure hospitalization, Cardiovascular death

Secondary/protocol endpoint

Time to first occurrence of a composite HF and Major Adverse Cardiovascular Events (MACE) end-point consisting of: CV death, HF hospitalisation or urgent HF visit, Nonfatal Myocardial Infraction (MI), Nonfatal stroke

Time frame:From baseline (week 0) to 165 weeks

4-point MACE

time to event, event

componentsCardiovascular death, Heart-failure hospitalization, Non-fatal MI, Non-fatal stroke

Secondary/protocol endpoint

Time to all-cause death

Time frame:From baseline (week 0) to 165 weeks

All-cause death

time to event, event

SNOMED 419620001

Heart failure

2 endpoints

Primary/protocol endpoint

Time to first occurrence of a composite HF endpoint consisting of HF hospitalisation or urgent HF visit

Time frame:From baseline (week 0) to 165 weeks

Heart-failure composite

time to event, event

componentsHeart-failure hospitalization, Urgent heart-failure visit

SNOMED 84114007

Secondary/protocol endpoint

Change in Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS) for participants with baseline KCCQ-CSS score less than (<) 80 points

Time frame:From baseline (week 0) to week 52

KCCQ clinical summary

change from baseline, improvement

Renal / kidney

1 endpoint

Secondary/protocol endpoint

Change in estimated Glomerular Filtration Rate (eGFR) (creatinine and cystatin C-based Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021) for participants with baseline eGFR< 60 millilitre per minute per 1.73 square metre (mL/min/1.73 m^2)

Time frame:From baseline (week 0) to week 78

eGFR, change

change from baseline, improvement

LOINC 98979-8

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.