Study to Assess Safety, Tolerability and Efficacy of SC Administered MBL949 in Obese Participants With or Without T2DM

Study Overview
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Brief Summary
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This is a multi-center, randomized, placebo-controlled, participant-and-investigator-blinded, sponsor open-label study in obese participants with or without Type 2 Diabetes Mellitus.

Detailed Description
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The study comprises a screening/baseline period of up to 35 days (5 weeks), a 14-week treatment period in which participants will be administered MBL949 or placebo at 8 biweekly intervals starting on Day 1 and a 10-week follow-up period

Official Title
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A Randomized, Placebo-controlled, Participant-and-investigator- Blinded, Sponsor Open-label Study to Evaluate the Safety, Tolerability, and Efficacy With Different Dosing Regimens of Subcutaneously Administered MBL949 in Obese Participants With or Without Type 2 Diabetes Mellitus

Conditions
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Obesity

Intervention / Treatment
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* Drug: MBL949
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index: ≥ 32 kg/m2, weight ≥ 77 kg, stable body weight i.e., less than 1.5 kg self-reported change within 90 days Diagnosed T2DM as documented by medical history and confirmed by Investigator and with diagnosed duration < 10 yrs, HbA1c ≤ 9%, and fasting C-peptide ≥ 0.2 ng/ml If treated for T2DM, treatment must be limited to diet and exercise and treatment with one of the following anti-diabetic agents (stable for 90 days prior to randomization): Metformin SGLT2i inhibitors (if prescribed as the first line, ie. single agent) DDP4 inhibitors Acarbose Exclusion Criteria: Vitals at screening: systolic blood pressure less than 95 mm Hg or greater than 155 mm Hg diastolic blood pressure less than 60 mg Hg or greater than 95 mm Hg pulse rate less than 56 or greater than 110 bpm History of bariatric surgery, Roux-en-Y Gastric Bypass, Sleeve Gastrectomy, gastric banding, and any other intrabdominal procedures designed for weight loss at screening History of myocardial infarction with 2 years of screening Diet attempts within 90 days before screening Participation in organized weight reduction program within 6 months of screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MBL949 Arm 1<br>One dose C followed by two doses E followed by five doses D of MBL949 | Drug: MBL949<br>* subcutaneous injections administered for 14 weeks<br>|
| Active Comparator: MBL949 Arm 2<br>Two doses C followed by six doses D of MBL949 | Drug: MBL949<br>* subcutaneous injections administered for 14 weeks<br>|
| Active Comparator: MBL949 Arm 3<br>One dose G followed by seven doses D of MBL949 | Drug: MBL949<br>* subcutaneous injections administered for 14 weeks<br>|
| Active Comparator: MBL949 Arm 4<br>One dose A followed by seven doses B of MBL949 | Drug: MBL949<br>* subcutaneous injections administered for 14 weeks<br>|
| Active Comparator: MBL949 Arm 5<br>One dose C followed by two doses E followed by five doses F of MBL949 | Drug: MBL949<br>* subcutaneous injections administered for 14 weeks<br>|
| Placebo Comparator: Placebo<br>MBL949 Arm 1, MBL949 Arm 2 and placebo to be enrolled in a 1:1:1 ratio MBL949 Arm 3, MBL949 Arm 4 and placebo to be enrolled in a 1:1:1 ratio If MBL949 Arm 1 is tolerated, MBL949 Arm 5 to be enrolled with a 2:1 ratio (MBL:placebo) within each stratum. MBL949 arm 5 will have 12 participants and 6 participants added to placebo arm | Drug: Placebo<br>* Placebo Comparator to MLB949<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of Adverse Events | Primary endpoints for safety and tolerability are occurrences and severities of adverse events by number and percentage of participants reported after the first dose of study medication or events present prior to treatment but increase in severity | Baseline to Day 169 | 
| Change-from-baseline in weight | Baseline weight is defined as the last weight measurement before dosing in kilograms | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, weight loss