Efficacy and Safety of MET097 in Adults with Overweight or Obesity: A Phase 3, Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate the efficacy of MET097, a GLP-1RA, in individuals with obesity by demonstrating superiority over placebo in the percent change from baseline body weight at Week 64. This assessment is clinically significant for determining the potential of a once-weekly subcutaneous injection to achieve sustained weight reduction. Secondary objectives include:

• Evaluation of total body weight reduction from baseline at Week 64 and Week 84.
• Assessment of changes in lipids and lipoproteins at Week 64.
• Measurement of changes in systolic blood pressure at Week 64.
• Evaluation of physical functioning via patient reported outcomes at Week 64.

The study population consists of 2606 adult participants, including both males and females, diagnosed with obesity. Eligible individuals are aged 18 years or older and must present with a body mass index (BMI) of $\ge$30 kg/m$^2$, or a BMI between 27.0 kg/m$^2$ and <30.0 kg/m$^2$ accompanied by at least one weight-related comorbidity. These comorbidities include hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. Participants are required to adhere to specific lifestyle modifications, such as dietary restrictions and exercise plans, throughout the duration of the trial.

This Phase 3, multi-center, randomized, controlled trial is designed to evaluate the efficacy and safety of MET097, a fully-biased ultra long-acting GLP-1RA, in adults with obesity or overweight. The study utilizes a subcutaneous injection of either the test product or a placebo once weekly. Participants will undergo a screening visit to assess eligibility based on body mass index (BMI) and weight-related co-morbidities, such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. The primary objective is to demonstrate superiority in the percent change from baseline body weight at Week 64. Secondary endpoints include changes in body weight, fasting triglycerides, non-high-density lipoprotein-cholesterol, systolic blood pressure, and physical function scores. The study includes assessments at Week 84 to evaluate long-term outcomes. The total duration of participant involvement and study procedures is designed to monitor safety and efficacy through the final follow-up visits.

The experimental treatment consists of MET097, a fully-biased ultra long-acting glucagon-like peptide-1 receptor agonist. The medication is administered as a solution for injection at a concentration of 5 mg/mL via subcutaneous injection on a once-weekly dosing schedule.

The comparator is a matching placebo used for comparison against the active test substance.

The efficacy of MET097 in patients with obesity will be evaluated through several parameters. The primary endpoint is the percent change from baseline in body weight at Week 64. Secondary endpoints include the absolute change in body weight in kilograms at Week 64 and Week 84. Additional secondary assessments at Week 64 consist of the occurrence of specific weight reduction percentages, changes in fasting triglycerides, and changes in non-high-density lipoprotein cholesterol.

Further efficacy assessments at Week 64 involve the measurement of systolic blood pressure and the evaluation of the physical function domain score using the Short Form 36 health survey. The study also evaluates the percent change from baseline in body weight at Week 84.