Phase 2 Randomized, Double-Blind, Dose-Finding Study of Petrelintide Versus Placebo in Obesity or Overweight Patients with Weight-Related Comorbidities

The primary objective of this randomized, double-blind, Phase 2 trial is to evaluate the **dose-response** of increasing doses of petrelintide compared to placebo on body weight. This evaluation is conducted in the context of a reduced-calorie diet and increased physical activity over a 28-week period. The clinical relevance of this objective lies in its potential to inform optimal dosing strategies for petrelintide, which may enhance weight management in individuals with obesity or overweight and associated comorbidities.

Secondary objectives include:

• Comparing the efficacy of petrelintide versus placebo on body weight and other efficacy parameters.
• Assessing the safety and tolerability of petrelintide when used as an adjunct to lifestyle modifications.

The clinical trial involves a total of **290 participants** who are being studied for **weight management**. The study population includes both male and female adults aged 18 years and older. Participants are required to have a **body mass index (BMI)** of 30.0 kg/m² or higher, or a BMI of 27.0 kg/m² or higher with the presence of comorbidities such as hypertension or dyslipidemia. The trial population was selected based on their ability to comply with protocol requirements, including self-administration of the investigational medicinal product (IMP). Participants are expected to adhere to a reduced-calorie diet and increased physical activity as part of the study's lifestyle considerations. The trial includes individuals from a vulnerable population, ensuring a comprehensive understanding of the treatment's effects across diverse groups. The selection criteria ensure that participants are capable of providing informed consent and are not pregnant or lactating, with women of childbearing potential required to use effective contraceptive methods throughout the trial.

The clinical trial is a **randomized, double-blind, controlled** study designed to evaluate the efficacy of **petrelintide** compared to placebo in individuals with obesity or overweight accompanied by weight-related comorbidities. The trial is structured as a Phase 2, dose-finding study, with the primary objective of assessing the dose-response of increasing doses of petrelintide on body weight, in conjunction with a reduced-calorie diet and increased physical activity over a 28-week period. The trial is expected to commence recruitment on November 6, 2024, and conclude by July 6, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, body mass index, and the presence of comorbidities like hypertension or dyslipidemia. Following successful screening, participants will be randomized to receive either petrelintide or placebo, administered as a **solution for injection** via the **subcutaneous** route. The trial will include regular follow-up visits to monitor safety, adherence, and efficacy, with the primary endpoint being the percentage change in body weight from baseline to week 28. Secondary endpoints include achieving a body weight loss of at least 5% and 10% from baseline to week 28.

The expected duration of participant involvement is approximately 54 weeks, encompassing the treatment period and follow-up. Conditions that may lead to early termination from the study include non-compliance with protocol requirements, adverse events, or withdrawal of consent. The trial is not classified as low intervention, and it is essential for participants to comply with the protocol, including the self-administration of the investigational medicinal product (IMP) using a vial and syringe. The study aims to provide valuable insights into the management of weight through pharmacological intervention, contributing to the broader understanding of obesity treatment strategies.

The clinical trial involves the administration of **Petrelintide**, a **solution for injection** developed by Zealand Pharma. Petrelintide is a peptide-based medication with the active substance name **PETRELINTIDE**. It is administered subcutaneously and is available in two concentrations: 2 mg/ml and 10 mg/ml. The trial is designed to evaluate the dose-response of Petrelintide in participants with obesity or overweight conditions accompanied by weight-related comorbidities. The maximum treatment period for Petrelintide is 54 weeks, with the dosing schedule being once weekly. The trial aims to assess the effects of Petrelintide when used as an adjunct to a reduced-calorie diet and increased physical activity.

In addition to the experimental medication, a **placebo** is used as a comparator in the study. The placebo is designed to match the administration route and form of Petrelintide, although specific details about its composition are not provided. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators know which treatment is being administered, thereby reducing bias and enhancing the reliability of the trial results.

Efficacy in this clinical trial will be assessed by evaluating the impact of **petrelintide** on body weight in participants with obesity or overweight with weight-related comorbidities. The primary endpoint for efficacy assessment is the change in body weight percentage from baseline to week 28. Secondary endpoints include the proportion of participants achieving a body weight loss of at least 5% and 10% from baseline to week 28. These endpoints will be measured and collected at specified timepoints, with the primary focus on the 28-week mark. The trial is designed as a randomized, double-blind, Phase 2, dose-finding study, comparing once-weekly doses of petrelintide with a placebo, alongside a reduced-calorie diet and increased physical activity. The efficacy parameters will be analyzed to determine the dose-response relationship of petrelintide in achieving weight reduction in the target population.