A Study to Test the Effect of Survodutide (BI 456906) on Cardiovascular Safety in People With Overweight or Obesity (SYNCHRONIZE™ - CVOT)

• ClinicalTrials.gov Identifier: NCT06077864
• Recruitment Status: Recruiting
• First Posted: October 11, 2023
• Last Update Posted: May 14, 2024
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: September 27, 2023
• First Posted Date: October 11, 2023
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: November 17, 2023
• Estimated Primary Completion Date: March 12, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 2023)

Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (to demonstrate non-inferiority) [ Time Frame: up to Week 114 ]

Heart failure events (HFE) includes hospitalisation for heart failure (HHF), emergency room visit, urgent care visit, or urgent outpatient heart failure (HF) visit (5-point major adverse cardiac event (5P-MACE)) CV-Cardiovascular MI-Myocardial infarction

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 23, 2024)

• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, or non-fatal MI (3-point major adverse cardiac event (3P-MACE)) (to demonstrate non-inferiority) [ Time Frame: up to Week 114 ]
• Absolute change in systolic blood pressure (SBP) (mmHg) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in waist circumference (cm) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) from baseline to Week 72 in trial participants with HF at baseline [ Time Frame: At Baseline and at Week 72 ]
  KCCQ-TSCC scale score range is from 0 to 100 where low score means patient not doing well and higher score means patient doing better.
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (to demonstrate superiority) [ Time Frame: up to Week 114 ]
• Percentage change in body weight from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in diastolic blood pressure (DBP) (mmHg) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in aspartate aminotransferase (AST) (U/L) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in alanine aminotransferase (ALT) (U/L) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in glycosylated haemoglobin A1c (HbA1c) (mmol/mol) from baseline to Week 72 in trial participants with type 2 diabetes mellitus (T2DM) [ Time Frame: Baseline and at Week 72 ]
• Absolute change in HbA1c (%) from baseline to Week 72 in trial participants with T2DM [ Time Frame: Baseline and at Week 72 ]
• Time to onset of T2DM in trial participants without T2DM at baseline [ Time Frame: up to Week 114 ]
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, or ischaemia related coronary revascularisation (4-point major adverse cardiac event (4P-MACE)) [ Time Frame: up to Week 114 ]
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, or HFE (3P-MACE+ HFE) [ Time Frame: up to Week 114 ]
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, or non-fatal MI (3P-MACE) [ Time Frame: up to Week 114 ]
• Time to first occurrence of adjudicated CV death or adjudicated HFE [ Time Frame: up to Week 114 ]
• Time to first occurrence of adjudicated CV death or adjudicated HHF [ Time Frame: up to Week 114 ]
• Time to first occurrence of adjudicated HFE [ Time Frame: up to Week 114 ]
• Time to adjudicated CV death [ Time Frame: up to Week 114 ]
• Time to all-cause mortality [ Time Frame: up to Week 114 ]
• Time to first occurrence of adjudicated non-fatal MI [ Time Frame: up to Week 114 ]
• Time to first occurrence of adjudicated non-fatal stroke [ Time Frame: up to Week 114 ]
• Time to first occurrence of adjudicated ischaemia related coronary revascularisation [ Time Frame: up to Week 114 ]
• Achievement of body weight reduction ≥5% from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Achievement of body weight reduction ≥10% from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Achievement of body weight reduction ≥15% from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• A composite of death, number of adjudicated HFEs, time to first adjudicated HFE and change from baseline in KCCQ-TSS at 72 weeks assessed by the win ratio in trial participants with HF at baseline [ Time Frame: At baseline and at 72 Weeks ]
  Win ratio will be assessed as below: The primary efficacy endpoint will be analyzed using the clinical benefit approach comparing every participant in the BI 456906 arm to every participant in the placebo arm to determine a winner. A winner in the pair-wise comparison has a delayed time to the occurrence of death; if that cannot be determined, a winner has fewer HFEs; if the number of HFEs is the same a winner has a delayed time to the occurrence of first HFE; if that rule does not determine a winner, a winner has a more favorable (less increase or more decrease) change in KCCQ-CSS between baseline and at 72 weeks, otherwise the pair will be recorded as tied. The estimated net benefit (win ratio is then calculated as the total number of wins in the BI 456906 group across all strata divided by the total number of losses) will be provided. KCCQ-TSCC scale score range is from 0 to 100 where low score means patient not doing well and higher score means patient doing better.

Original Secondary Outcome Measures (submitted: October 4, 2023)

• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, or non-fatal MI (3-point major adverse cardiac event (3P-MACE)) (to demonstrate non-inferiority) [ Time Frame: up to Week 114 ]
• Absolute change in systolic blood pressure (SBP) (mmHg) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in waist circumference (cm) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) from baseline to Week 72 in trial participants with HF at baseline [ Time Frame: At Baseline and at Week 72 ]
  KCCQ-TSCC scale score range is from 0 to 100 where low score means patient not doing well and higher score means patient doing better.
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (to demonstrate superiority) [ Time Frame: up to Week 114 ]
• Percentage change in body weight from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in diastolic blood pressure (DBP) (mmHg) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in aspartate aminotransferase (AST) (U/L) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in alanine aminotransferase (ALT) (U/L) from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Absolute change in glycosylated haemoglobin A1c (HbA1c) (mmol/mol) from baseline to Week 72 in trial participants with type 2 diabetes mellitus (T2DM) [ Time Frame: Baseline and at Week 72 ]
• Absolute change in HbA1c (%) from baseline to Week 72 in trial participants with T2DM [ Time Frame: Baseline and at Week 72 ]
• Time to onset of T2DM in trial participants without T2DM at baseline [ Time Frame: up to Week 114 ]
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, or ischaemia related coronary revascularisation (4-point major adverse cardiac event (4P-MACE)) [ Time Frame: up to Week 114 ]
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, or HFE (3P-MACE+ HFE) [ Time Frame: up to Week 114 ]
• Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, or non-fatal MI (3P-MACE) [ Time Frame: up to Week 114 ]
• Time to first occurrence of CV death or HFE [ Time Frame: up to Week 114 ]
• Time to first occurrence of CV death or HHF [ Time Frame: up to Week 114 ]
• Time to first occurrence of HFE [ Time Frame: up to Week 114 ]
• Time to CV death [ Time Frame: up to Week 114 ]
• Time to all-cause mortality [ Time Frame: up to Week 114 ]
• Time to first occurrence of non-fatal MI [ Time Frame: up to Week 114 ]
• Time to first occurrence of non-fatal stroke [ Time Frame: up to Week 114 ]
• Time to first occurrence of ischaemia related coronary revascularisation [ Time Frame: up to Week 114 ]
• Achievement of body weight reduction ≥5% from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Achievement of body weight reduction ≥10% from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• Achievement of body weight reduction ≥15% from baseline to Week 72 [ Time Frame: Baseline and at Week 72 ]
• A composite of death, number HFEs (including HHFs, urgent HF visits, and unplanned outpatient visits), time to first HFE and change from baseline in KCCQ-TSS at 72 weeks assessed by the win ratio in trial participants with HF at baseline [ Time Frame: At baseline and at 72 Weeks ]
  Win ratio will be assessed as below: The primary efficacy endpoint will be analyzed using the clinical benefit approach comparing every participant in the BI 456906 arm to every participant in the placebo arm to determine a winner. A winner in the pair-wise comparison has a delayed time to the occurrence of death; if that cannot be determined, a winner has fewer HFEs; if the number of HFEs is the same a winner has a delayed time to the occurrence of first HFE; if that rule does not determine a winner, a winner has a more favorable (less increase or more decrease) change in KCCQ-CSS between baseline and at 72 weeks, otherwise the pair will be recorded as tied. The estimated net benefit (win ratio is then calculated as the total number of wins in the BI 456906 group across all strata divided by the total number of losses) will be provided. KCCQ-TSCC scale score range is from 0 to 100 where low score means patient not doing well and higher score means patient doing better.

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

Descriptive Information

• Brief Title: A Study to Test the Effect of Survodutide (BI 456906) on Cardiovascular Safety in People With Overweight or Obesity (SYNCHRONIZE™ - CVOT)
• Official Title: A Phase 3, Randomised, Double-blind, Parallel-group, Event-driven, Cardiovascular Safety Study With BI 456906 Administered Subcutaneously Compared With Placebo in Participants With Overweight or Obesity With Established Cardiovascular Disease (CVD) or Chronic Kidney Disease, and/or at Least Two Weight-related Complications or Risk Factors for CVD

Brief Summary

This study is open to adults who are at least 18 years old and have a body mass index (BMI)bof 27 kg/m2 or more. People can take part if they have cardiovascular or chronic kidney disease. People who have at least 2 health problems related to their weight or risks of cardiovascular disease can participate. Participants must have previously tried to lose weight by changing their diet.

The purpose of this study is to find out whether people with overweight or obesity who take a medicine called survodutide (BI 456906) are less or more likely to develop serious cardiovascular problems. It also aims to find out whether health parameters like blood pressure improve. Overweight and obesity are linked to cardiovascular disease. Survodutide is a medicine that is developed to help people with obesity or overweight to lose weight.

Participants are divided into 3 groups of almost equal size. 2 groups get different doses of survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Every participant has a 2 in 3 chance of getting survodutide. Participants inject survodutide or placebo under the skin once a week. All participants also receive counselling on diet and physical activity.

Participants are in the study for up to 2 years and 3 months. During this time, it is planned that participants visit the study site up to 21 times and attend remote visits by video calls. During these visits, the doctors check participants' cardiovascular and overall health. The results are compared between survodutide and placebo groups. The study staff also takes note of any unwanted effects.

• 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); Primary Purpose: Treatment
• Condition: Obesity

Intervention

• Drug: survodutide
  once weekly subcutaneous injection
  Other Name: BI 456906
• Drug: Placebo
  once weekly subcutaneous injection

Study Arms

• Experimental: survodutide 3.6 mg
  Intervention: Drug: survodutide
• Experimental: survodutide 6.0 mg
  Intervention: Drug: survodutide
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 4, 2023): 4935
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2, 2026
• Estimated Primary Completion Date: March 12, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female, age ≥18 years at the time of signing informed consent, and at least the legal age of consent in countries where it is >18 years.
2. Body mass index (BMI) ≥27 kg/m2 at screening with established cardiovascular disease (CVD) and/or at least 2 weight-related complications or risk factors for CVD OR BMI ≥30 kg/m2 at screening with established CVD or chronic kidney disease (CKD), and/or at least 2 weight-related complications or risk factors for CVD.

Further inclusion criteria apply.

Exclusion criteria:

1. Previous treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists within 3 months before screening.
2. Type 1 diabetes.
3. Less than 3 months between the last dose of GLP-1R agonists and GLP-1R agonist/insulin/glucose-dependent insulinotropic polypeptide (GIP) combinations and screening.
4. Known clinically significant gastric emptying abnormality (e.g., severe diabetic gastroparesis or gastric outlet obstruction).

Further exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Boehringer Ingelheim; 1-800-243-0127; clintriage.rdg@boehringer-ingelheim.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Finland, Germany, Greece, Hong Kong, Hungary, India, Ireland, Italy, Japan, Kazakhstan, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Saudi Arabia, Slovakia, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT06077864
• Other Study ID Numbers: 1404-0040; 2022-502442-27-00 ( Registry Identifier: CTIS ); U1111-1289-0174 ( Registry Identifier: WHO registry )
• Has Data Monitoring Committee: Yes

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: Once the criteria in section 'time frame' are fulfilled, researchers can use the following link https:// www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'.For study data -1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• URL: https://www.mystudywindow.com/msw/datasharing

• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: May 2024