Dapiglutide for the treatment of obesity (DREAM): a randomised, double-blind, placebo-controlled, investigator-initiated trial

The primary objective of this study is to evaluate the effects of **dapiglutide** at doses of 4 mg and 6 mg on the change in body weight, expressed as a percentage, in individuals with **obesity**. This is clinically relevant as obesity is a significant risk factor for numerous health conditions, and effective weight management can lead to improved health outcomes and reduced morbidity. The study is designed as a randomized, double-blind, placebo-controlled trial to ensure the reliability and validity of the results.

The clinical trial focuses on individuals diagnosed with **obesity**, aiming to assess the impact of dapiglutide on body weight reduction. The study population includes both male and female participants aged between 18 and 75 years, with a **BMI** of 30 kg/m² or higher. Participants have a documented history of at least one attempt to lose weight. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria emphasize the inclusion of adults with a significant commitment to weight management, without specific lifestyle restrictions such as diet or physical activity. The trial population was selected based on these criteria to ensure a representative sample of individuals affected by obesity.

The clinical trial is designed to evaluate the effects of **dapiglutide** on body weight in individuals with **obesity**. This study is a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial involves the administration of dapiglutide in a solution for injection form, with a maximum daily dose of 6 mg and a total dose not exceeding 54 mg over a 12-week period. The trial is expected to conclude by July 31, 2024, with recruitment having commenced on December 5, 2022.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is assessed based on criteria such as age (18-75 years), a body mass index (BMI) of 30 kg/m² or higher, and a history of at least one attempt to lose weight. Following the inclusion visit, participants will be randomized to receive either dapiglutide or a placebo. Subsequent follow-up visits will be scheduled to monitor changes in body weight, as well as secondary endpoints such as body weight reduction of at least 5%, and changes in fasting serum/plasma concentrations of gut permeability biomarkers and inflammation markers, including high-sensitivity C-reactive protein (CRP) and interleukin-6 (IL-6).

The expected duration of participant involvement is approximately 12 weeks, aligning with the maximum treatment period. Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with study procedures, or withdraw consent. The end-of-study visit will involve a final assessment of the primary and secondary endpoints, ensuring comprehensive data collection for analysis. This trial is categorized as a Phase II trial, focusing on the efficacy and safety of dapiglutide in the specified population.

The clinical trial involves the administration of **dapiglutide**, an investigational medication, for the treatment of obesity. Dapiglutide is formulated as a **solution for injection** and is administered via the **subcutaneous route**. The dosing regimen includes two dosage levels: 4 mg and 6 mg, with a maximum daily dose of 6 mg and a cumulative maximum dose of 54 mg over the treatment period. The treatment duration is set for a maximum of 12 weeks. Dapiglutide is classified as a new chemical entity and is produced by Zealand Pharma. The active substance, dapiglutide, is derived from a protein of other origin.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled trial. The placebo is designed to match the pharmaceutical form of dapiglutide, being a solution for injection, and is administered subcutaneously. The placebo serves to maintain the study's blinding and to provide a baseline for evaluating the efficacy of dapiglutide in reducing body weight. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in the clinical trial titled "Dapiglutide for the treatment of obesity (DREAM): a randomised, double-blind, placebo-controlled, investigator-initiated trial" will be assessed primarily through the **change in body weight** percentage. This primary endpoint will be measured to evaluate the effects of 4 mg and 6 mg doses of dapiglutide. Secondary endpoints include achieving a body weight reduction of at least 5%, as well as changes in fasting serum/plasma concentrations of gut permeability biomarkers, specifically LPS, and inflammation markers such as high-sensitivity CRP and Interleukin (IL)-6. These parameters will be collected and analyzed to determine the efficacy of dapiglutide in treating obesity. The trial is designed to ensure objective and reliable assessment of these endpoints, contributing to the understanding of dapiglutide's therapeutic potential.