A Study to Test Whether BI 456906 Helps Japanese People Living With Obesity Disease

Study Overview
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Brief Summary
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This study is open to adults who are at least 18 years old and have a body mass index (BMI) of 35 kg/m² or more and at least one health problem related to their weight, or a BMI of 27 kg/m² or more and at least two health problems related to their weight. People who have either type 2 diabetes, high blood pressure, or increased blood lipids can take part in this study. Only people who have previously not managed to lose weight by changing their diet can participate. The purpose of this study is to find out whether a medicine called survodutide (BI 456906) helps people living with obesity disease to lose weight. Participants are divided into 3 groups by chance, like drawing names from a hat. 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 their skin once a week for about one and a half years. In addition to the study medicine, all participants receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for about 1 year and 7 months. During this time, it is planned that participants visit the study site up to 14 times and receive 6 phone calls by the site staff. The doctors check participants' health and take note of any unwanted effects. The participants' body weight is regularly measured. The results are compared between the groups to see whether the treatment works.

Official Title
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A Phase III, Randomised, Double-blind, Parallel-group, 76-week, Efficacy and Safety Study of BI 456906 Administered Subcutaneously Compared With Placebo in Patients With Obesity Disease in Japanese

Conditions
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Obesity

Intervention / Treatment
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* Drug: BI 456906
* Drug: Placebo matching BI 456906


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female, age ≥18 years at the time of signing informed consent Body Mass Index (BMI) ≥35 kg/m² at screening with the presence of at least one obesity-related comorbidities (treated or untreated) according to the Japan Society for the Study of Obesity (JASSO) guideline OR BMI ≥27 kg/m² at screening with the presence of at least two obesity-related comorbidities (treated or untreated) according to the JASSO guideline For all trial patients, at least one co-morbidity should be the following (i)-(iii). i. Type 2 diabetes mellitus (T2DM) Diagnosed with T2DM (defined as Glycosylated haemoglobin A1c (HbA1c) ≥6.5% [≥48 mmol/mol]) at least 180 days prior to screening HbA1c ≥6.5% (48 mmol/mol) and <10% (86 mmol/mol) as measured by the central laboratory at screening Currently treated with either: diet and exercise alone or stable treatment (for at least 3 months prior to screening) with metformin, SGLT-2i, acarbose, sulfonylurea, or glitazone as single agent therapy, or up to 3 antihyperglycaemia medications (metformin, SGLT-2i, acarbose, sulfonylurea, or glitazone) according to local label ii. Hypertension iii. Dyslipidaemia History of at least one self-reported unsuccessful dietary effort to lose body weight Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial Woman of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use will be provided in the patient information. In the investigator's opinion, patients are well-motivated, capable, and willing to: Learn how to self-inject the Investigational medicinal product (IMP), as required for this protocol (persons with physical limitations who are not able to perform the injections must have the assistance of an individual trained to inject the IMP) OR Inject the IMP or accept injection from a designated person Follow study procedures for the duration of the study, including, but not limited to: follow lifestyle advice (for example, dietary restrictions and exercise and exercise plan), maintain a diary, and complete required questionnaires, and handle the IMP as described in the instructions for use (IFU) Exclusion criteria: Obesity: Body weight change (self-reported) >5% within 3 months before screening Treatment with any medication for the indication obesity within 3 months before screening Previous or planned (during the trial period) treatment for obesity with surgery or a weight loss device, or prior surgery of the gastrointestinal (GI) tract that could interfere with body weight The following are allowed: (1) liposuction and/or abdominoplasty, if performed >1 year before screening, (2) lap banding, if the band has been removed >1 year before screening, (3) intragastric balloon, if the balloon has been removed >1 year before screening, (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed >1 year before screening, (5) appendectomy, (6) simple hernia repair, or (7) cholecystectomy. Have obesity induced by other endocrinologic disorders (i.e. Cushing Syndrome) or diagnosed monogenetic or syndromic forms of obesity (i.e. melanocortin 4 receptor deficiency, leptin deficiency, or Prader Willi Syndrome) Glycaemia: For trial patients without T2DM: History of T1DM or T2DM or treatment with glucose lowering agent started within 3 months before screening For trial patients with T2DM: History of T1DM Treatment with any medication for the indication of T2DM other than stated in the inclusion criteria within 3 months before screening (i.e. insulin, amylin analogues, GLP-1R agonists, GLP-1R agonist/insulin/GIP combinations, and DPP-4i) New initiation of any other glucose-lowering investigational drug within 3 months prior to screening for this trial Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 456906 (survodutide) - 3.6 mg<br> | Drug: BI 456906<br>* once weekly subcutaneous injection<br>* Other names: survodutide;|
| Experimental: BI 456906 (survodutide) - 6.0 mg<br> | Drug: BI 456906<br>* once weekly subcutaneous injection<br>* Other names: survodutide;|
| Placebo Comparator: Placebo group<br> | Drug: Placebo matching BI 456906<br>* once weekly subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in body weight from baseline to Week 76 |  | at baseline, at week 76 | 
| Achievement of body weight reduction ≥5% (yes/no) from baseline to Week 76 |  | at baseline, at week 76 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of body weight reduction ≥10% (yes/no) from baseline to Week 76 |  | at baseline, at week 76 | 
| Achievement of body weight reduction ≥15% (yes/no) from baseline to Week 76 |  | at baseline, at week 76 | 
| Achievement of body weight reduction ≥20% (yes/no) from baseline to Week 76 |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in body weight (kg) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in body mass index (BMI) (kg/m²) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in waist circumference measured at umbilical level (cm) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in waist circumference measured at midway between the lower rib margin and the iliac crest (cm) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in systolic blood pressure (SBP) (mmHg) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in diastolic blood pressure (DBP) (mmHg) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in Capacity to Resist domain score of the Eating Behaviour Patient reported outcome (PRO) | The Capacity to Resist domain score of the Eating Behaviour Patient reported outcome (PRO) (units on a scale) will be derived as the sum of items in the domain (possible responses being 0=Not at all, 1=A little, 2=Moderately, 3=A lot, 4=Extremely). The domain score is ranging between 0 and 24 and a higher score indicates a lower capacity to resist. | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in Eating Behaviour PRO total score | The Eating Behaviour PRO total score (units on a scale) will be derived from the Desire to Eat and Capacity to Resist domain as the sum of all items (possible responses being 0=Not at all, 1=A little, 2=Moderately, 3=A lot, 4=Extremely). Each domain consists of 6 items. The score is ranging between 0 and 48 and a higher score indicates a worse eating behaviour (greater desire to eat and/or lower capacity to resist). | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in glycosylated haemoglobin A1c (HbA1c) (%) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in HbA1c (mmol/mol) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in fasting plasma glucose (FPG) (mg/dL) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in fasting plasma insulin (FPI) (mIU/L) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in total cholesterol (mg/dL) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in high density lipoprotein (HDL) (mg/dL) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in low density lipoprotein (LDL) (mg/dL) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in very-low-density lipoprotein (VLDL) (mg/dL) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in triglycerides (mg/dL) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in free fatty acids (mg/dL) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in alanine aminotransferase (ALT) (U/L) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in aspartate aminotransferase (AST) (U/L) |  | at baseline, at week 76 | 
| Relative change from baseline to Week 76 in liver fat content (%), assessed by Magnetic resonance imaging proton density fat fraction (MRI-PDFF) |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in total fat mass (percentage [%]) assessed by MRI for body composition |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in total fat mass (volume [L]) assessed by MRI for body composition |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in lean body mass (percentage [%]) assessed by MRI for body composition |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in lean body mass (volume [L]) assessed by MRI for body composition |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in visceral fat mass (percentage [%]) assessed by MRI for body composition |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in visceral fat mass (volume [L]) assessed by MRI for body composition |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in skeletal muscle mass (percentage [%]) assessed by MRI for body composition |  | at baseline, at week 76 | 
| Absolute change from baseline to Week 76 in skeletal muscle mass (volume [L]) assessed by MRI for body composition |  | at baseline, at week 76 |