Clinical trial NCT06176365: A Study to Test Whether Survodutide Helps Japanese People Living With Obesity Disease
Official title: A Phase III, Randomised, Double-blind, Parallel-group, 76-week, Efficacy and Safety Study of Survodutide Administered Subcutaneously Compared With Placebo in Patients With Obesity Disease in Japanese
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Obesity
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-12-19
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion criteria:

1. Male or female, age ≥18 years at the time of signing informed consent
2. 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
3. History of at least one self-reported unsuccessful dietary effort to lose body weight
4. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
5. 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.
6. 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:

1. Body weight change (self-reported) \>5% within 3 months before screening
2. Treatment with any medication for the indication obesity within 3 months before screening
3. 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.
4. 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:
5. History of T1DM or T2DM or treatment with glucose lowering agent started within 3 months before screening

   For trial patients with T2DM:
6. History of T1DM
7. 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)
8. New initiation of any other glucose-lowering investigational drug within 3 months prior to screening for this trial

Further exclusion criteria apply.

Primary outcomes:
measure: Percentage change in body weight from baseline to Week 76
timeFrame: at baseline, at week 76
measure: Achievement of body weight reduction ≥5% (yes/no) from baseline to Week 76
timeFrame: at baseline, at week 76
Secondary outcomes:
measure: Achievement of body weight reduction ≥10% (yes/no) from baseline to Week 76
timeFrame: at baseline, at week 76
measure: Achievement of body weight reduction ≥15% (yes/no) from baseline to Week 76
timeFrame: at baseline, at week 76
measure: Achievement of body weight reduction ≥20% (yes/no) from baseline to Week 76
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in body weight (kg)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in body mass index (BMI) (kg/m²)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in waist circumference measured at umbilical level (cm)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in waist circumference measured at midway between the lower rib margin and the iliac crest (cm)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in systolic blood pressure (SBP) (mmHg)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in diastolic blood pressure (DBP) (mmHg)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in "Capacity to Resist" domain score of the Eating Behaviour Patient reported outcome (PRO)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in Eating Behaviour PRO total score
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in glycosylated haemoglobin A1c (HbA1c) (%)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in HbA1c (mmol/mol)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in fasting plasma glucose (FPG) (mg/dL)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in fasting plasma insulin (FPI) (mIU/L)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in total cholesterol (mg/dL)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in high density lipoprotein (HDL) (mg/dL)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in low density lipoprotein (LDL) (mg/dL)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in very-low-density lipoprotein (VLDL) (mg/dL)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in triglycerides (mg/dL)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in free fatty acids (mg/dL)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in alanine aminotransferase (ALT) (U/L)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in aspartate aminotransferase (AST) (U/L)
timeFrame: at baseline, at week 76
measure: Relative change from baseline to Week 76 in liver fat content (%), assessed by Magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in total fat mass (percentage [%]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in total fat mass (volume [L]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in lean body mass (percentage [%]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in lean body mass (volume [L]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in visceral fat mass (percentage [%]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in visceral fat mass (volume [L]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in contractile thigh muscle volume (percentage [%]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in contractile thigh muscle volume (volume [L]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in sub-cutaneous fat volume (volume [L]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
measure: Absolute change from baseline to Week 76 in sub-cutaneous fat volume (percentage [%]) assessed by MRI for body composition
timeFrame: at baseline, at week 76
Other outcomes:
Locations:
city: Aichi, Nagoya
country: Japan
facility: Hosokawa Surgery Clinic
city: Aichi, Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Chiba, Chiba
country: Japan
facility: Chiba University Hospital
city: Gifu, Gifu
country: Japan
facility: Gifu University Hospital
city: Hokkaido, Obihiro
country: Japan
facility: Jiyugaoka Yamada Clinic
city: Hyogo, Amagasaki
country: Japan
facility: Yamasaki Family Clinic
city: Hyogo, Kobe
country: Japan
facility: Kobe University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Motomachi Takatsuka Naika Clinic
city: Kumamoto, Kumamoto
country: Japan
facility: Morinagaueno Clinic
city: Kumamoto, Kumamoto
country: Japan
facility: Yoshimura Clinic
city: Kyoto, Kyoto
country: Japan
facility: Medical Corporation KEISEIKAI Kajiyama Clinic
city: Kyoto, Kyoto
country: Japan
facility: Ijinkai Takeda General Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Osaka, Suita
country: Japan
facility: OCROM Clinic
city: Saitama, Tokorozawa
country: Japan
facility: Saino Clinic
city: Tokyo, Chiyoda-ku
country: Japan
facility: Dojinkinenkai Meiwa Hospital
city: Tokyo, Chiyoda-ku
country: Japan
facility: Suidoubashi Medical Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo Center Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Fukuwa Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo Asbo Clinic
city: Tokyo, Hachioji
country: Japan
facility: New Medical Research System Clinic
city: Tokyo, Nerima-ku
country: Japan
facility: Shimamura Kinen Hospital
city: Tokyo, Shinjuku-ku
country: Japan
facility: Clinical Research Hospital Tokyo
city: Tokyo, Shinjuku-ku
country: Japan
facility: HS Clinic
city: Tokyo, Shinjyuku-ku
country: Japan
facility: ToCROM Clinic
city: Tokyo, Suginami-ku
country: Japan
facility: Shinei Medical Healthcare Clinic
city: Tokyo, Toshima-ku
country: Japan
facility: Ikebukuro Metropolitan Clinic
Study officials:
References: