A Phase 3, randomised, double-blind, parallel-group, 76-week, efficacy and safety study of BI 456906 administered subcutaneously compared with placebo in participants with overweight or obesity without type 2 diabetes

The primary objective of this Phase 3, randomized, double-blind, parallel-group study is to evaluate the **efficacy**, safety, and tolerability of **survodutide** as an adjunct to a reduced-calorie diet and increased physical activity, compared to placebo, in participants with a body mass index (BMI) ≥30 kg/m² or a BMI ≥27 kg/m² with at least one weight-related complication, but without type 2 diabetes mellitus (T2DM). The primary aim is to demonstrate the superiority of survodutide at both low and high doses against placebo. This is clinically relevant as it addresses the need for effective weight management strategies in individuals with obesity, a condition associated with numerous health risks.

Secondary objectives include demonstrating the superiority of survodutide at low and high doses against placebo concerning the secondary endpoints specified in the clinical trial protocol. These objectives further explore the potential benefits of survodutide in managing obesity-related outcomes beyond weight loss alone.

The clinical trial involves a total of **596 participants** who are being studied to assess the efficacy, safety, and tolerability of survodutide as an adjunct to a reduced-calorie diet and increased physical activity, compared to a placebo. The study population includes both **male and female** participants aged **18 years and older**, with a **Body Mass Index (BMI)** of **30 kg/m² or higher**, or a BMI of **27 kg/m²** with at least one weight-related complication such as hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, or non-alcoholic steatohepatitis (NASH). Participants were selected based on their history of at least one self-reported unsuccessful dietary effort to lose body weight. The trial includes individuals from a vulnerable population, and the participants are required to adhere to a reduced-calorie diet and increased physical activity regimen as part of the study protocol. The sponsor has not provided additional information regarding specific lifestyle considerations or further demographic details.

The clinical trial is designed as a **randomized**, **double-blind**, parallel-group study to evaluate the efficacy and safety of **BI 456906** administered subcutaneously compared with placebo in participants with overweight or **obesity** without type 2 diabetes. The trial will span a duration of 76 weeks, with the primary objective being to demonstrate the superiority of **survodutide** in achieving weight reduction. Participants will be randomly assigned to receive either the investigational product or placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study.

The trial will commence with an inclusion (screening) visit, where participants will be assessed against the inclusion criteria, such as being 18 years or older and having a **BMI** of 30 kg/m² or higher, or a BMI of 27 kg/m² with at least one weight-related complication. Following successful screening, participants will be enrolled and begin the treatment phase. The study will include several follow-up visits to monitor the participants' progress, assess safety, and collect data on primary and secondary endpoints, such as percentage change in body weight and achievement of specific weight reduction milestones.

The end-of-study visit will occur at the conclusion of the 76-week period, where final assessments will be conducted to evaluate the overall efficacy and safety of the treatment. Participant involvement is expected to last the entire duration of the trial unless conditions arise that necessitate early termination, such as adverse events or withdrawal of consent. The trial's design and procedures are structured to ensure rigorous evaluation of the investigational product's impact on weight management in the target population.

The clinical trial involves the administration of **BI 456906**, a **solution for injection** developed by Boehringer Ingelheim International. This experimental medication is characterized by its active substance, **survodutide**, which is a protein of other origin. The pharmaceutical form is a solution for injection, and the route of administration is subcutaneous. The dosing schedule varies, with a maximum treatment period ranging from 4 to 60 weeks, depending on the specific protocol within the trial. The dosage is measured in milligrams, although specific daily and total dose amounts are not provided. The trial aims to assess the efficacy, safety, and tolerability of survodutide as an adjunct to a reduced-calorie diet and increased physical activity in participants with a body mass index (BMI) of 30 kg/m² or higher, or a BMI of 27 kg/m² with at least one weight-related complication, but without type 2 diabetes mellitus (T2DM).

In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-blind nature of the trial. The placebo does not contain any active substance and serves as a control to evaluate the true efficacy of BI 456906. The administration route and frequency for the placebo are designed to mimic those of the experimental medication, ensuring that any observed effects can be attributed to the active treatment rather than the administration process itself.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. This monitoring is crucial for maintaining the integrity of the study results and for accurately assessing the efficacy and safety of the experimental treatment compared to the placebo. The trial is conducted under strict regulatory standards to ensure the safety and well-being of all participants.

The efficacy of the clinical trial will be assessed through a series of predefined primary and secondary endpoints. The primary endpoints include the percentage change in body weight from baseline to Week 76 and the achievement of a body weight reduction of at least 5% from baseline to Week 76. Secondary endpoints will evaluate further weight reduction milestones, including reductions of 10%, 15%, and 20% from baseline to Week 76. Additionally, absolute changes from baseline to Week 76 will be measured in body weight (kg), waist circumference (cm), systolic blood pressure (SBP) (mmHg), and scores from the Eating Behaviour Patient-Reported Outcome (PRO) tool, specifically the "Capacity to Resist" domain and the total score.

The trial will involve the administration of **survodutide** as an adjunct to a reduced-calorie diet and increased physical activity, compared to a placebo. The efficacy parameters will be collected and analyzed at the specified timepoint of Week 76. The trial is designed to demonstrate the superiority of survodutide in achieving these endpoints in participants with a Body Mass Index (BMI) of 30 kg/m² or higher, or a BMI of 27 kg/m² with at least one weight-related complication, excluding those with type 2 diabetes mellitus (T2DM). The trial will be conducted over a 76-week period, with the estimated end date set for January 16, 2026.