Efficacy and Safety of Zenagamtide in Participants with Obesity: A Randomized Controlled Trial to Evaluate Weight Maintenance

The primary objective of this study is to confirm the superiority of zenagamtide versus placebo regarding the change in body weight in participants with obesity. 5: Efficacy.

Secondary objectives include the evaluation of the following outcomes:

• Change in waist circumference.
• Changes in body mass index (BMI).
• Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP).
• Alterations in glucose metabolism, lipids, and high-sensitivity C-reactive protein (hsCRP).
• Impact on physical functioning and weight-related quality of life.
• Assessment of safety and tolerability of the investigational product as an adjunct to a reduced-calorie diet and increased physical activity. 4: Safety.

The study involves a total of 275 participants consisting of male and female individuals. The population is comprised of patients diagnosed with obesity. Eligible subjects must be at least 18 years of age at the time of signing informed consent. Inclusion is contingent upon a body mass index of ≥ 30 kg/m2. The primary objective is to evaluate the superiority of NNC0487-0111 versus placebo regarding the change in body weight.

This Phase III clinical trial is designed to evaluate the efficacy and safety of zenagamtide compared to a placebo in participants with obesity. The study aims to confirm the superiority of the test product regarding the relative change in body weight. The intervention involves a subcutaneous administration of the solution for injection in a pre-filled pen on a weekly basis. Participants will undergo a screening period to ensure eligibility based on Body Mass Index and other clinical criteria. The research methodology includes monitoring various secondary endpoints, such as waist circumference, systolic blood pressure, and glycated haemoglobin levels. Study involvement is expected to occur within the timeframe of the trial, which has an estimated end date of June 2028. The trial includes follow-up assessments to track clinical changes and the occurrence of treatment emergent adverse events.

The investigational medicinal product is zenagamtide, administered as a solution for injection in pre-filled pen. The medication is delivered via the subcutaneous route on a once weekly dosing schedule for participants with obesity.

A placebo is utilized as a comparator treatment in this study.

The efficacy assessment for participants with obesity is primarily focused on the relative change in body weight. Secondary efficacy parameters include the change in body mass index (BMI), waist circumference, and absolute change in body weight. Metabolic evaluations consist of assessments of glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin, and lipids, which encompass total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, and triglycerides. Additionally, high-sensitivity C-reactive protein (hsCRP) will be measured.

Cardiovascular parameters are evaluated through changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Patient-reported outcomes are assessed using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT), specifically focusing on the physical function score, physical composite score, psychosocial composite score, and total score. The SF-36v2® Health Survey Acute is also utilized to measure the physical functioning score. The CCI is incorporated as an additional metric for evaluation.