Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity

Study Overview
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Brief Summary
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This study will look at how the participants daily life is affected by their heart failure. The study will also look at the change in participants body weight from the start to the end of the study. This is to compare the effect on heart failure symptoms and on body weight in people taking semaglutide (a new medicine) to people taking dummy medicine. 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 choices including healthy food and physical activity. The study will last for approximately 59 weeks. Participants will have 11 clinic visits and 1 phone call with the study doctor. Women: Women cannot take part if they are 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

Conditions
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Obesity

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 percentage at screening Exclusion Criteria: A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records Haemoglobin A1c (HbA1c) greater than or equal to 6.5 percentage (48 mmol/mol) based on latest available value from medical records, no older than 3 months or if unavailable a local measurement at screening

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>All participants will receive either semaglutide 2.4 mg once weekly or placebo once weekly as add-on to standard of care. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose. | Drug: Semaglutide<br>* Semaglutide will be injected into a skin fold, in the stomach, thigh or upper arm once a week at the same day of the week (to the extent possible) throughout the trial. Dose gradually escalated from 0.25 mg until target dose. The study will last for approximately 59 weeks.<br>|
| Placebo Comparator: Placebo (semaglutide)<br>All participants will receive either semaglutide 2.4 mg once weekly or placebo once weekly as add-on to standard of care. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose. | Drug: Placebo (semaglutide)<br>* Placebo will be injected into a skin fold, in the stomach, thigh or upper arm once a week at the same day of the week (to the extent possible) throughout the trial. The study will last for approximately 59 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 (no unit, range; 0-100 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 six-minute walking distance | 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) | 
| Hierarchial 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) | 
| Hierarchial composite of difference at least 15 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 10 in KCCQ clinical summary score change from baseline to 52 weeks | 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 (CRP) | Ratio to baseline (no unit) | From baseline (week -2) to end of treatment (week 52) | 
| Subject achieving 10 percentage weight loss or more (Yes/No) | Count of subjects | From baseline (week 0) to end of treatment (week 52) | 
| Subject achieving 15 percentage weight loss or more (Yes/No) | Count of subjects | From baseline (week 0) to end of treatment (week 52) | 
| Subject achieving 20 percentage weight loss or more (Yes/No) | Count of subjects | From baseline (week 0) to end of treatment (week 52) | 
| Subject improving 5 points or more in KCCQ clinical summary score (Yes/No) | Count of subjects | From baseline (week 0) to end of treatment (week 52) | 
| Subject improving 10 points or more in KCCQ clinical summary score (Yes/No) | Count of subjects | From baseline (week 0) to end of treatment (week 52) | 
| Change in KCCQ overall summary score | Score (no unit, range; 0-100 where the score 100 means the least burden for the participant) | From baseline (week 0) to end of treatment (week 52) | 
| Subject achieving threshold for clinically meaningful within-subject change in KCCQ-CSS | Count of subjects | From baseline (week 0) to end of treatment (week 52) | 
| Subject achieving threshold for clinically meaningful within-subject change in 6MWD | Count of subjects | From baseline (week 0) to end of treatment (week 52) | 
| Change in systolic blood pressure (SBP) | mmHg | From baseline (week -2) to end of treatment (week 52) | 
| Change in waist circumference | cm | From baseline (week 0) to end of treatment (visit 52) |