The study looks at people who have heart failure with preserved ejection fraction or heart failure with mildly reduced ejection fraction together with obesity. The medication being tested is a weekly injection given under the skin called NNC0487-0111. Some participants receive the active medication while others receive a matching placebo; all participants continue their usual heart medicines.
The aim is to find out whether adding the new medication to standard treatment lowers the chance of dying from heart‑related causes, being hospitalized for heart failure, or needing urgent care for heart failure.
Participants will receive a dose once a week for several months and will attend regular visits where simple checks such as blood pressure, weight, and short questionnaires are done. The study follows each person over time to see how often the listed heart events occur and to monitor safety through routine lab tests.
1study entry
after consent you are entered into the study and a series of baseline measurements are taken. these may include a physical exam, blood tests, a questionnaire about your heart‑failure symptoms, and a review of any current medicines.
2randomization
based on a computer‑generated list you are assigned to receive either zenagamtide (the test drug) or a matching placebo. the assignment is unknown to you and the staff who give the injection.
3weekly injection
each week you receive a single subcutaneous (under the skin) injection using a pre‑filled pen. the injection contains either zenagamtide or the placebo. the exact amount of drug is determined by the study protocol and is the same each week.
the injection is given once every 7 days and continues for the duration of the study, which may last up to about three years (from may 2026 to august 2029) unless you withdraw early or the study ends for other reasons.
4regular follow‑up visits
you attend scheduled clinic visits, often every month or as instructed, to allow the study team to check your safety and how well the treatment is working.
at each visit blood samples are taken to measure kidney function (e.g. eGFR), heart‑failure biomarkers, and any other safety indicators.
you also complete a questionnaire called the KCCQ‑CSS, which asks about your symptoms and quality of life. this is done at baseline and at later visits to track any changes.
5assessment of outcomes
throughout the study the occurrence of major events such as cardiovascular death, heart‑failure hospital admission, urgent heart‑failure visits, non‑fatal heart attack or stroke is recorded.
these events are used to determine whether the test drug reduces the risk compared with the placebo.
6study completion or early exit
the study ends for you when the overall study period finishes, when you experience a defined event, or if you choose to stop participating.
at the final visit a complete set of assessments similar to the baseline visit is performed, and you are informed about the next steps for your regular medical care.
Who Can Join the Study?
Body Mass Index (BMI) ≥ 30 kg/m² – you must have a BMI of 30 or higher, which means you are classified as having obesity based on a calculation that compares your weight to your height.
Diagnosis of heart failure with preserved or mid‑range ejection fraction (HFpEF or HFmrEF) – you need a medical record confirming this type of heart failure, which means the heart’s pumping ability is still relatively normal.
New York Heart Association (NYHA) class II‑IV – you must have symptoms of heart failure that range from mild limitation of physical activity (class II) to marked limitation or inability to carry out any physical activity (class III‑IV).
Stable condition at screening – your heart failure symptoms should not be getting worse or changing rapidly at the time of the study visit.
Adult age range – you must be an adult participant as defined by the study’s age requirements.
Both males and females are eligible – the study accepts participants of any gender.
If you have type 2 diabetes (T2D), you must have been diagnosed with it at least 30 days before screening – this ensures that the diabetes condition is established before joining the trial.
Who Cannot Join the Study?
Having a heart attack (myocardial infarction), stroke, unstable chest pain (unstable angina), or worsening heart failure that required a hospital stay or IV loop diuretic medicines within the last 30 days.
Having eye problems from diabetes (diabetic retinopathy or maculopathy) that needed laser treatment, eye surgery, or anti‑vascular endothelial growth factor (anti‑VEGF) injections within the past 180 days, or that are expected to need such treatment within 180 days after screening, and that must be confirmed by an eye exam performed within 90 days.
Using multiple daily insulin shots or an insulin pump (continuous subcutaneous insulin infusion).
Having a blood‑sugar control test result (HbA1c) higher than 10 % (86 mmol/mol) at screening.
Planning any artery‑opening procedures (coronary, carotid, or peripheral artery revascularization) during the study period that are already known at the screening visit.
Having heart failure caused by specific diseases such as infiltrative cardiomyopathy (e.g., sarcoid or amyloid), arrhythmogenic right‑ventricular cardiomyopathy, Takotsubo cardiomyopathy, Chagas disease, genetic hypertrophic cardiomyopathy, obstructive cardiomyopathy, active heart‑muscle inflammation (myocarditis), constrictive pericarditis, cardiac tamponade, or uncorrected moderate‑to‑severe heart valve disease.
Having severe lung disease, including primary pulmonary hypertension, chronic pulmonary embolism, or severe chronic obstructive pulmonary disease (COPD) that requires home oxygen, ongoing oral steroid medicines, or a hospital stay for a COPD flare‑up within the past year.
Having any other medical condition that the doctor believes is causing the heart‑failure symptoms, such as anemia or low thyroid hormone (hypothyroidism).
Want to learn more about this study or check if you can participate? Contact us.
Trial status
Country
Status
Recruitment Start
Bulgaria
Recruiting
11.05.2026
Czechia
Recruiting
11.05.2026
Denmark
Recruiting
11.05.2026
France
Recruiting
11.05.2026
Germany
Recruiting
11.05.2026
Greece
Recruiting
11.05.2026
Italy
Recruiting
11.05.2026
Poland
Recruiting
11.05.2026
Spain
Recruiting
11.05.2026
The Netherlands
Recruiting
11.05.2026
Trial locations
NNC0487-0111 is an investigational medicine being tested in this study. It is a liquid that is injected under the skin using a pre‑filled pen. The active ingredient in the product is called zenagamtide. In the trial participants receive this injection once a week, in addition to the usual medicines and care doctors give for heart failure. The purpose of adding NNC0487-0111 is to see if it can lower the chances of dying from heart problems, being hospitalized for heart failure, or needing an urgent visit because of worsening heart failure in people who have a type of heart failure called HFpEF or HFmrEF and who are also overweight or obese.
Heart failure with preserved ejection fraction – This condition occurs when the heart muscle is stiff and cannot relax properly, so blood does not fill the heart efficiently. Fluid can build up in the lungs and legs, causing shortness of breath and swelling. Symptoms often start during physical activity and become more noticeable over time. The condition usually progresses slowly, with episodes of worsening fluid buildup that may improve with rest.
Heart failure with mildly reduced ejection fraction – In this form of heart failure the heart’s pumping ability is slightly below normal, leading to reduced blood flow to the body. Fluid may accumulate in the lungs and extremities, causing breathlessness and ankle swelling. Early signs are often mild and may be mistaken for normal tiredness. Over months or years the reduction in pumping ability can become more pronounced, leading to more frequent fluid‑related symptoms.
Obesity – Obesity is defined by an excess amount of body fat that accumulates over time. The condition develops gradually as caloric intake consistently exceeds energy expenditure. It can cause increasing strain on the heart, joints, and breathing as weight adds extra load. Without changes in lifestyle, the amount of body fat typically continues to rise, making everyday activities more difficult.
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Bulgaria 
Czechia 
Denmark 
France 
Germany 
Greece 
Italy 
Poland 
Spain 
The Netherlands 
