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

Phase 3

Active, not recruiting

• Conditions: Obesity
• Interventions: Drug: Placebo; Drug: survodutide

• Registration Number: NCT06077864
• Lead Sponsor: Boehringer Ingelheim

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 available

Study Timeline

• Study First Submitted: 2023-09-27
• Study First Submitted QC: 2023-10-04
• Study First Posted: 2023-10-11
• Study Start: 2023-11-20
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-09
• Last Update Posted: 2025-07-10
• Primary Completion: 2026-04-06
• Study Completion: 2026-06-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 5563

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
survodutide 3.6 mg	survodutide	-
survodutide 6.0 mg	survodutide	-

Primary Outcome Measures

Name	Time	Method
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)	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

Secondary Outcome Measures

Name	Time	Method
Time to first occurrence of adjudicated CV death or adjudicated HFE	up to Week 114
Time to first occurrence of adjudicated CV death or adjudicated HHF	up to Week 114
Time to first occurrence of adjudicated HFE	up to Week 114
Time to adjudicated CV death	up to Week 114
Time to all-cause mortality	up to Week 114
Time to first occurrence of adjudicated non-fatal MI	up to Week 114
Time to first occurrence of adjudicated non-fatal stroke	up to Week 114
Time to first occurrence of adjudicated ischaemia related coronary revascularisation	up to Week 114
Achievement of body weight reduction ≥5% from baseline to Week 72	Baseline and at Week 72
Achievement of body weight reduction ≥10% from baseline to Week 72	Baseline and at Week 72
Achievement of body weight reduction ≥15% from baseline to Week 72	Baseline and at Week 72
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))	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)	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 (3-point major adverse cardiac event (3P-MACE)) (to demonstrate non-inferiority)	up to Week 114
Absolute change in systolic blood pressure (SBP) (mmHg) from baseline to Week 72	Baseline and at Week 72
Absolute change in waist circumference (cm) from baseline to Week 72	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	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)	up to Week 114
Percentage change in body weight from baseline to Week 72	Baseline and at Week 72
Absolute change in diastolic blood pressure (DBP) (mmHg) from baseline to Week 72	Baseline and at Week 72
Absolute change in aspartate aminotransferase (AST) (U/L) from baseline to Week 72	Baseline and at Week 72
Absolute change in alanine aminotransferase (ALT) (U/L) from baseline to Week 72	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)	Baseline and at Week 72
Absolute change in HbA1c (%) from baseline to Week 72 in trial participants with T2DM	Baseline and at Week 72
Time to onset of T2DM in trial participants without T2DM at baseline	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)	up to Week 114
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	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.

Trial Locations

Locations (536)

Cardiology P.C.; 🇺🇸 Birmingham, Alabama, United States

AMR Daphne; 🇺🇸 Daphne, Alabama, United States

AMR Mobile; 🇺🇸 Mobile, Alabama, United States

Mobile Heart Specialists, PC; 🇺🇸 Mobile, Alabama, United States

The Institute for Liver Health, LLC; 🇺🇸 Chandler, Arizona, United States

Clinical Research Institute of Arizona, LLC; 🇺🇸 Sun City West, Arizona, United States

AMR Phoenix; 🇺🇸 Tempe, Arizona, United States

Arizona Liver Health-Tucson-67516; 🇺🇸 Tucson, Arizona, United States

Yuma Clinical Trials; 🇺🇸 Yuma, Arizona, United States

Lynn Institute of the Ozarks; 🇺🇸 Little Rock, Arkansas, United States

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