ZENAGAMTIDE for Heart failure with preserved ejection fraction (HFpEF) | Heart failure with mildly reduced ejection fraction (HFmrEF) | Obesity

Inclusion criteria

• {"criterion_text":"- 1. Body Mass Index (BMI) ≥30 kg/m2 at screening."}
• {"criterion_text":"- 2. Diagnosis of HF with New York Heart Association (NYHA) class II-IV and in stable condition at screening, at the discretion of the investigator."}
• {"criterion_text":"- CCI"}
• {"criterion_text":"- CCI"}
• {"criterion_text":"- For participants with T2D at screening: 5. Diagnosed with T2D ≥ 30 days before screening."}
• {"criterion_text":"- CCI"}

Exclusion criteria

• {"criterion_text":"- 1. Myocardial infarction (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"}
• {"criterion_text":"- 10. 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."}
• {"criterion_text":"- 11. Treatment with multiple daily insulin injections or continuous subcutaneous insulin infusion."}
• {"criterion_text":"- 12. HbA1c >10% (86 mmol/mol) as measured by local or central laboratory at screening."}
• {"criterion_text":"- CCI"}
• {"criterion_text":"- CCI"}
• {"criterion_text":"- 3. Coronary, carotid, or peripheral artery revascularization planned during the study period and known at screening (visit 1)."}
• {"criterion_text":"- 4. 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."}
• {"criterion_text":"- 5. 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."}
• {"criterion_text":"- 6. Any other condition judged by the investigator to be the cause of HF symptoms (e.g., anaemia, hypothyroidism)."}
• {"criterion_text":"- CCI"}
• {"criterion_text":"- CCI"}
• {"criterion_text":"- 9. History of type 1 diabetes."}

Primary endpoints

• {"endpoint_text":"- Time to first occurrence of a composite HF endpoint consisting of: CV death, HF hospitalisation or urgent HF visit","definition_or_measurement_approach":"Time-to-event measured from randomisation to first occurrence of the composite heart-failure endpoint (cardiovascular death, heart-failure hospitalization, or urgent heart-failure visit)."}

Secondary endpoints

• {"endpoint_text":"- Time to first occurrence of a composite HF and MACE endpoint consisting of: CV death, HF hospitalisation or urgent HF visit, Nonfatal MI, Nonfatal stroke","definition_or_measurement_approach":"Time-to-event measured from randomisation to first occurrence of the composite HF and major adverse cardiovascular events (MACE: CV death, HF hospitalization or urgent HF visit, nonfatal MI, nonfatal stroke)."}
• {"endpoint_text":"- Change in KCCQ-CSS for participants with baseline KCCQ‑CSS score <80 points","definition_or_measurement_approach":"Change from baseline in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) in participants with baseline score <80."}
• {"endpoint_text":"- Change in eGFR (creatinine and cystatin C‑based CKD‑EPI 2021) for participants with baseline eGFR<60 mL/min/1.73 m2","definition_or_measurement_approach":"Change from baseline in estimated glomerular filtration rate calculated by CKD‑EPI 2021 formula using creatinine and cystatin C, in participants with baseline eGFR <60 mL/min/1.73 m2."}
• {"endpoint_text":"- Time to all-cause death","definition_or_measurement_approach":"Time-to-event measured from randomisation to death from any cause."}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}

Methods

• Site-based recruitment via cardiology clinics and hospitals (numerous hospital and clinic sites listed per country).
• Local and country-specific recruitment materials: posters, A3/A4 posters, study booklets, letters to participants, informed-consent guides (k1/k2 recruitment documents available per Member State).
• Direct-to-patient service (logistics/dispatch) provided by Marken Limited (direct-to-patient service noted in sponsor third-party duties).
• Patient-facing materials and partner information sheets available in local languages to support enrolment.

Bulgaria

Earliest CTIS Part Ii Submission Date

21-04-2026

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

13

Number Of Participants

272

Czechia

Earliest CTIS Part Ii Submission Date

26-02-2026

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

50

Number Of Participants

170

Denmark

Earliest CTIS Part Ii Submission Date

22-04-2026

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

5

Number Of Participants

90

France

Earliest CTIS Part Ii Submission Date

09-04-2026

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

8

Number Of Participants

36

Germany

Earliest CTIS Part Ii Submission Date

01-04-2026

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

19

Number Of Participants

180

Greece

Earliest CTIS Part Ii Submission Date

30-01-2026

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

77

Number Of Participants

195

Italy

Earliest CTIS Part Ii Submission Date

03-04-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

27

Number Of Participants

210

Spain

Earliest CTIS Part Ii Submission Date

03-04-2026

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

24

Number Of Participants

218

Netherlands

Earliest CTIS Part Ii Submission Date

21-04-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

2

Number Of Participants

121

Poland

Earliest CTIS Part Ii Submission Date

15-04-2026

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

13

Number Of Participants

500

Primary sponsor

Full Name

Novo Nordisk A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Responsible for sample management, conducting laboratory tests, ensuring data accuracy, maintaining quality and regulatory compliance, and reporting results.

Name

Iqvia Biotech LLC

Responsibilities

eCOA

Name

4G Clinical B.V.

Responsibilities

RTSM supplier

Name

Marken Limited

Responsibilities

Direct to patient service

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Responsible for sample management, conducting laboratory tests, ensuring data accuracy, maintaining quality and regulatory compliance, and reporting results.","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Celerion Switzerland AG","duties_or_roles":"Special laboratory for pharmacokinetic samples","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Affidea Piraeus Biopathological","duties_or_roles":"Exams to be performed eye examination with fundus photography or by slit-lamp biomicroscopy examination using a pre-corneal or corneal contact lens. Optical coherence tomography (OCT)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Marken Limited","duties_or_roles":"Direct to patient service","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Vivos Technology Limited","duties_or_roles":"External independent statistical service provider","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"CRF supplier, Global safety Database Supplier","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"RTSM supplier","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"AG Mednet Inc.","duties_or_roles":"Event Adjudication","organisation_type":"Pharmaceutical company"}