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

• ClinicalTrials.gov Identifier: NCT04916470
• Recruitment Status: Completed
• First Posted: June 7, 2021
• Last Update Posted: March 15, 2024
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: June 1, 2021
• First Posted Date: June 7, 2021
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: June 15, 2021
• Actual Primary Completion Date: October 11, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 1, 2021)

• Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Score on a scale of 0 to 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 6-minute walking distance [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Measured in 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
• Hierarchical 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.
• Hierarchical composite of difference at least 15 inKansas City Cardiomyopathy Questionnaire (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) ]
  Measured as 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 [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  Presented as ratio to baseline
• Participant achieving 10% weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Participant achieving 15% weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Participant achieving 20% weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Participant improving 5 points or more in KCCQ clinical summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Participant 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 participants
• Change in KCCQ overall summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Score on a scale of 0 to 100 where the score 100 means the least burden for the participant.
• Participant 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 participants
• Participant achieving threshold for clinically meaningful within-subject change in 6MWD [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Change in waist circumference [ Time Frame: From baseline (week 0) to end of treatment (visit 52) ]
  Measured in centimetre (cm)
• Change in systolic blood pressure [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  Measured in millimetre of mercury (mmHg)
• Change in glycated haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Measured in percentage (%)-point
• Number of treatment emergent severe or clinically significant hypoglycaemia episodes [ Time Frame: From baseline (week 0) to end of trial (week 57) ]
  Count of events

Original Secondary Outcome Measures (submitted: June 1, 2021)

• Change in C-Reactive Protein [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  Presented as ratio to baseline
• Change in 6-minute walking distance [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Measured in metres
• Participant achieving 10% weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Participant achieving 15% weight loss or more (Yes/No) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Participant improving 5 points or more in KCCQ clinical summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Count of participants
• Participant 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 participants
• Change in KCCQ overall summary score [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Score on a scale of 0 to 100 where the score 100 means the least burden for the participant.
• Change in waist circumference [ Time Frame: From baseline (week 0) to end of treatment (visit 52) ]
  Measured in centimetre (cm)
• Change in systolic blood pressure [ Time Frame: From baseline (week -2) to end of treatment (week 52) ]
  Measured in millimetre of mercury (mmHg)
• Change in glycated haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to end of treatment (week 52) ]
  Measured in percentage (%)-point
• Number of treatment emergent severe or clinically significant hypoglycaemia episodes [ Time Frame: From baseline (week 0) to end of trial (week 57) ]
  Count of events

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

Descriptive Information

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

Brief Summary

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.

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

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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

Primary Purpose: Treatment

• Condition: Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2

Intervention

• Drug: Semaglutide
  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.
• Drug: Placebo (Semaglutide)
  Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly for 52 weeks.

Study Arms

• Experimental: Semaglutide 2.4 mg once weekly (OW)
  Participants will receive semaglutide injections for 52 weeks.
  Intervention: Drug: Semaglutide
• Placebo Comparator: Semaglutide placebo OW
  Participants will receive semaglutide placebo injections for 52 weeks.
  Intervention: Drug: Placebo (Semaglutide)

• Publications *: Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Christensen L, Davies M, Hovingh KG, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Petrie MC. Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype. JACC Heart Fail. 2023 Aug;11(8 Pt 1):1000-1010. doi: 10.1016/j.jchf.2023.05.010. Epub 2023 May 21.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 1, 2021): 610
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 11, 2023
• Actual Primary Completion Date: October 11, 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% 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.

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, Austria, Canada, Czechia, Germany, Hungary, India, Israel, Italy, Japan, Netherlands, Poland, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT04916470
• Other Study ID Numbers: EX9536-4773; U1111-1257-5069 ( Other Identifier: World Health Organization (WHO) ); 2020-004170-22 ( EudraCT Number )
• 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: March 2024