Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity (STEP-HFpEF)

• ClinicalTrials.gov Identifier: NCT04788511
• Recruitment Status: Completed
• First Posted: March 9, 2021
• Last Update Posted: September 11, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: March 5, 2021
• First Posted Date: March 9, 2021
• Last Update Posted Date: September 11, 2023
• Actual Study Start Date: March 16, 2021
• Actual Primary Completion Date: April 18, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 5, 2021)

• Change in KCCQ (Kansas City Cardiomyopathy Questionnaire ) clinical summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Score (no unit, range; 0-100 where the score 100 means the least burden for the participant)
• Change in body weight [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Percentage

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 20, 2022)

• Change in six-minute walking distance [ Time Frame: From baseline (week 0) to end of treatment (week 52 ]
  Metres
• Hierarchical composite of time to all-cause death [ Time Frame: From baseline (week 0) to end of study (week 57) ]
  Measured as total wins for each treatment group
• Hierarchical composite of number of heart failure events requiring hospitalisation or urgent heart failure visit [ Time Frame: From baseline (week 0) to end of study (week 57) ]
  Measured as total wins for each treatment group.
• Hierarchial composite of time to first heart failure event requiring hospitalisation or urgent heart failure visit [ Time Frame: From baseline (week 0) to end of study (week 57) ]
  Measured as total wins for each treatment group.
• Hierarchial composite of difference at least 15 in KCCQ clinical summary score change from baseline to 52 weeks [ Time Frame: From baseline (week 0) to end of study (week 57) ]
  Measured as total wins for each treatment group
• Hierarchical composite of difference at least 10 in KCCQ clinical summary score change from baseline to 52 weeks [ Time Frame: From baseline (week 0) to end of study (week 57) ]
  Total wins for each treatment group.
• Hierarchical composite of difference at least 5 in KCCQ clinical summary score change from baseline to 52 weeks [ Time Frame: From baseline (week 0) to end of study (week 57) ]
  Measured as total wins for each treatment group
• Hierarchical composite of difference at least 30 metres in six minute walking distance change from baseline to 52 weeks (assessed by the win ratio) [ Time Frame: From baseline (week 0) to end of study (week 57) ]
  Measured as total wins for each treatment group
• Change in C-Reactive Protein (CRP) [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  Ratio to baseline (no unit)
• Subject achieving 10 percentage weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject achieving 15 percentage weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject achieving 20 percentage weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject improving 5 points or more in KCCQ clinical summary score (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject improving 10 points or more in KCCQ clinical summary score (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Change in KCCQ overall summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Score (no unit, range; 0-100 where the score 100 means the least burden for the participant)
• Subject achieving threshold for clinically meaningful within-subject change in KCCQ-CSS [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject achieving threshold for clinically meaningful within-subject change in 6MWD [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Change in systolic blood pressure (SBP) [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  mmHg
• Change in waist circumference [ Time Frame: From baseline (week 0) to end of treatment (visit 52) ]
  cm

Original Secondary Outcome Measures (submitted: March 5, 2021)

• Change in C-Reactive Protein (CRP) [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  Ratio to baseline (no unit)
• Change in six-minute walking distance [ Time Frame: From baseline (week 0) to end of treatment (week 52 ]
  Metres
• Subject achieving 10 percentage weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject achieving 15 percentage weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject improving 5 points or more in KCCQ clinical summary score (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Subject improving 10 points or more in KCCQ clinical summary score (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of subjects
• Change in KCCQ overall summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Score (no unit, range; 0-100 where the score 100 means the least burden for the participant)
• Change in systolic blood pressure (SBP) [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  mmHg
• Change in waist circumference [ Time Frame: From baseline (week 0) to end of treatment (visit 52) ]
  cm

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity
• Official Title: Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Sponsor staff involved in the clinical trial is masked according to company standard procedures.

Primary Purpose: Treatment

• Condition: Obesity

Intervention

• Drug: Semaglutide

  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.

• Drug: Placebo (semaglutide)

  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.

Study Arms

• Experimental: Semaglutide
  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.
  Intervention: Drug: Semaglutide
• Placebo Comparator: Placebo (semaglutide)
  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.
  Intervention: Drug: Placebo (semaglutide)

Publications *

• Borlaug BA, Kitzman DW, Davies MJ, Rasmussen S, Barros E, Butler J, Einfeldt MN, Hovingh GK, Moller DV, Petrie MC, Shah SJ, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Nunez J, Perna E, Schou M, Senni M, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023 Sep;29(9):2358-2365. doi: 10.1038/s41591-023-02526-x. Epub 2023 Aug 27.
• Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, Van der Meer P, von Lewinski D, Wolf D, Petrie MC; STEP-HFpEF Trial Committees and Investigators. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023 Sep 21;389(12):1069-1084. doi: 10.1056/NEJMoa2306963. Epub 2023 Aug 25.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 19, 2023): 529
• Original Estimated Enrollment (submitted: March 5, 2021): 516
• Actual Study Completion Date: April 18, 2023
• Actual Primary Completion Date: April 18, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Canada, Czechia, Denmark, Germany, Hungary, Israel, Netherlands, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04788511
• Other Study ID Numbers: EX9536-4665; U1111-1243-4358 ( Other Identifier: World Health Organization (WHO) ); 2019-004452-11 ( Registry Identifier: European Medicines Agency (EudraCT) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Current Responsible Party: Novo Nordisk A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: Novo Nordisk A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Transparency (dept. 1452); Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: September 2023