Efficacy and safety of zenagamtide once-weekly subcutaneous treatment for obesity in adults versus placebo

The primary objective of this study is to evaluate the efficacy of zenagamtide compared to placebo by assessing the change in body weight in participants with obesity. Secondary objectives include evaluating clinical outcomes such as body mass index, waist circumference, and physical functioning. Additionally, the study aims to assess metabolic and cardiovascular markers, specifically glucose metabolism, lipids, diastolic blood pressure, systolic blood pressure, and high-sensitivity C-reactive protein. The impact on weight-related quality of life will also be investigated. The safety and tolerability of the investigated doses will be compared against placebo. An extension phase will further evaluate changes in body weight, body mass index, physical functioning, waist circumference, systolic blood pressure, glucose metabolism, diastolic blood pressure, lipids, and high-sensitivity C-reactive protein.

This clinical trial involves a total of 850 participants diagnosed with obesity. The study population consists of both male and female individuals. Participants are within specific age ranges identified by codes 3 and 4. Inclusion requires a specified Body Mass Index (BMI) at the time of informed consent. The primary objective is to evaluate the superiority of various doses of NNC0487-0111 compared to a placebo regarding changes 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 utilizes a subcutaneous administration route via a solution for injection in pre-filled pen. The primary objective is to confirm the superiority of various doses of the investigational product over the placebo regarding the relative change in body weight. Secondary endpoints include assessments of body mass index, waist circumference, blood pressure, glycated haemoglobin, fasting plasma glucose, fasting insulin, and various lipid profiles. The research methodology aims to monitor treatment emergent adverse events to establish a safety profile. The estimated study period spans from April 2026 to July 2029.

The experimental treatment consists of zenagamtide, provided as a solution for injection in pre-filled pen. This investigational medicinal product is administered via subcutaneous injection on a once-weekly basis. The study utilizes multiple dose levels, designated as NNC0487-0111 B 10141, NNC0487-0111 B 10142, NNC0487-0111 B 10143, NNC0487-0111 B 10144, NNC0487-0111 B 10145, and NNC0487-0111 B 10146, to evaluate efficacy and safety in participants with obesity.

The comparator treatment is a placebo, which is used to assess the change in body weight relative to the active test substances.

The primary efficacy endpoint for this clinical trial in participants with obesity is the relative change in body weight. Secondary endpoints include measurements of body mass index (BMI), waist circumference, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Metabolic parameters assessed include glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin, and high-sensitivity C-reactive protein (hsCRP). Changes in lipids, specifically total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, and triglycerides, are also evaluated.

Patient-reported outcomes are assessed using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT), including the physical functioning score, psychosocial composite score, and total score. Additionally, physical functioning is evaluated via the SF-36v2® Health Survey Acute (SF-36v2 Acute). The study also monitors the number of treatment emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), and events leading to permanent treatment discontinuation.