Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes

Study Overview
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Brief Summary
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This study will look at how participants' daily life is affected by their heart failure. The study will also look at the change in participants' body weight. This study will compare the effect of semaglutide (a new medicine) compared to dummy medicine on body weight and heart failure symptoms. Participants will either get semaglutide or dummy medicine, which treatment participants get is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach area, thigh or upper arm. During the study participants will have talks with the study staff about healthy lifestyle and physical activity. The study will last for about 59 weeks, that is a little more than 1 year. Participants will have 12 clinic visits with the study doctor. At 6 of the visits participants will have blood samples taken. At 5 of the visits participants will be asked to fill in a questionnaire At 4 of the visits participants will have to do a 6-minute walking test At 3 of the visits participants will have a test to check the heart. participants will have their eyes checked before or at the start of the study and at the end of the study Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Official Title
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Effect of Semaglutide 2.4 mg Once-weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction, and Type 2 Diabetes

Conditions
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Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo (Semaglutide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age above or equal to 18 years at the time of signing informed consent. Body mass index (BMI) greater than or equal to 30.0 kg/m^2 New York Heart Association (NYHA) Class II-IV Left ventricular ejection fraction (LVEF) greater than or equal to 45% at screening Diagnosed with T2D greater than or equal to 90 days prior to the day of screening HbA1c of below or equal to 10.0% as measured at the screening visit Exclusion Criteria: A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 2.4 mg once weekly (OW)<br>Participants will receive semaglutide injections for 52 weeks. | Drug: Semaglutide<br>* Participants will receive semaglutide subcutaneous (s.c.; under the skin) injection(s) once-weekly for 52 weeks. Dose will be gradually increased to 2.4 mg: 0.25 mg from week 1 to 4, 0.5 mg from week 5 to 8, 1.0 mg from week 9 to 12, 1.7 mg from week 13 to 16 and 2.4 mg from week 17 to week 52.<br>|
| Placebo Comparator: Semaglutide placebo OW<br>Participants will receive semaglutide placebo injections for 52 weeks. | Drug: Placebo (Semaglutide)<br>* Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score | Score on a scale of 0 to 100 where the score 100 means the least burden for the participant. | From baseline (week 0) to end of treatment (week 52) | 
| Change in body weight | Percentage (%) | From baseline (week 0) to end of treatment (week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6-minute walking distance | Measured in metres | From baseline (week 0) to end of treatment (week 52) | 
| Hierarchical composite of time to all-cause death | Measured as total wins for each treatment group. | From baseline (week 0) to end of study (week 57) | 
| Hierarchical composite of number of heart failure events requiring hospitalisation or urgent heart failure visit | Measured as total wins for each treatment group | From baseline (week 0) to end of study (week 57) | 
| Hierarchical composite of time to first heart failure event requiring hospitalisation or urgent heart failure visit | Measured as total wins for each treatment group. | From baseline (week 0) to end of study (week 57) | 
| Hierarchical composite of difference at least 15 inKansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score change from baseline to 52 weeks | Measured as total wins for each treatment group. | From baseline (week 0) to end of study (week 57) | 
| Hierarchical composite of difference at least 10 in KCCQ clinical summary score change from baseline to 52 weeks | Measured as total wins for each treatment group. | From baseline (week 0) to end of study (week 57) | 
| Hierarchical composite of difference at least 5 in KCCQ clinical summary score change from baseline to 52 weeks | Measured as total wins for each treatment group. | From baseline (week 0) to end of study (week 57) | 
| Hierarchical composite of difference at least 30 metres in six-minute walking distance change from baseline to 52 weeks (assessed by the win ratio) | Measured as total wins for each treatment group. | From baseline (week 0) to end of study (week 57) | 
| Change in C-Reactive Protein | Presented as ratio to baseline | From baseline (week -2) to end of treatment (week 52) | 
| Participant achieving 10% weight loss or more (Yes/No) | Count of participants | From baseline (week 0) to end of treatment (week 52) | 
| Participant achieving 15% weight loss or more (Yes/No) | Count of participants | From baseline (week 0) to end of treatment (week 52) | 
| Participant achieving 20% weight loss or more (Yes/No) | Count of participants | From baseline (week 0) to end of treatment (week 52) | 
| Participant improving 5 points or more in KCCQ clinical summary score | Count of participants | From baseline (week 0) to end of treatment (week 52) | 
| Participant improving 10 points or more in KCCQ clinical summary score (Yes/No) | Count of participants | From baseline (week 0) to end of treatment (week 52) | 
| Change in KCCQ overall summary score | Score on a scale of 0 to 100 where the score 100 means the least burden for the participant. | From baseline (week 0) to end of treatment (week 52) | 
| Participant achieving threshold for clinically meaningful within-subject change in KCCQ-CSS | Count of participants | From baseline (week 0) to end of treatment (week 52) | 
| Participant achieving threshold for clinically meaningful within-subject change in 6MWD | Count of participants | From baseline (week 0) to end of treatment (week 52) | 
| Change in waist circumference | Measured in centimetre (cm) | From baseline (week 0) to end of treatment (visit 52) | 
| Change in systolic blood pressure | Measured in millimetre of mercury (mmHg) | From baseline (week -2) to end of treatment (week 52) | 
| Change in glycated haemoglobin (HbA1c) | Measured in percentage (%)-point | From baseline (week 0) to end of treatment (week 52) | 
| Number of treatment emergent severe or clinically significant hypoglycaemia episodes | Count of events | From baseline (week 0) to end of trial (week 57) |