Long-term Safety and Efficacy Evaluation of Glepaglutide in Adult Patients with Short Bowel Syndrome: A 104-Week Phase 3 Extension Study

The primary objective of this study is to evaluate the long-term **safety** of glepaglutide treatment in adult patients with **short bowel syndrome**. This is clinically relevant as it aims to ensure that the therapeutic use of glepaglutide does not pose significant health risks over extended periods, thereby supporting its potential as a viable long-term treatment option for this condition.

Secondary objectives include:

• Evaluating the maintenance of response concerning efficacy endpoints with glepaglutide 10 mg once weekly.
• Assessing the long-term immunogenicity of glepaglutide and its impact on pharmacokinetics, safety, and efficacy maintenance.

The clinical trial involves a total of **23 participants** diagnosed with **short bowel syndrome**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on their completion of the full treatment period of the extension trial EASE SBS 2 and their provision of signed informed consent. The trial does not specifically target a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. The primary objective of the trial is to evaluate the long-term safety of glepaglutide treatment.

The clinical trial is a **104-week**, multicenter, single-arm, long-term, Phase 3 extension study designed to evaluate the safety and efficacy of **glepaglutide** in adult patients with **short bowel syndrome** who have completed the EASE SBS 2 trial. The primary objective is to assess the long-term safety of glepaglutide treatment, with primary endpoints focusing on the incidence and type of adverse events (AEs) that occur or worsen following the initial visit. Secondary endpoints include the incidence of serious adverse events (SAEs) and AEs of special interest, changes in vital signs, electrocardiogram, hematology, biochemistry, urinalysis, and immunogenicity, as well as reductions in parenteral support (PS) volume and days on PS.

The trial employs a single-arm design, where all participants receive the investigational product, glepaglutide, administered as a **solution for injection** via subcutaneous use. The trial duration is estimated to conclude by November 30, 2028, with recruitment having commenced on April 30, 2021. Participants are expected to be involved for the entire 104-week period unless early termination is warranted due to specific conditions such as significant adverse reactions or withdrawal of consent.

Study visits are structured to include an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy parameters. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any ongoing safety concerns are addressed. Participants must have signed informed consent and completed the full treatment period of the EASE SBS 2 trial to be eligible. The trial is not categorized as low intervention and does not involve a pediatric formulation. Early termination from the study may occur if participants experience severe adverse events or choose to withdraw consent.

The clinical trial involves the administration of **Glepaglutide**, a synthetic peptide, as the experimental medication. **Glepaglutide** is provided in a **solution for injection** form, with a concentration of 20.0 mg/mL. The medication is administered via **subcutaneous use**. The maximum daily dose is 10 mg, and the total dose should not exceed 10 mg per day. The treatment period extends up to 104 weeks. The product is manufactured by Zealand Pharma and is not formulated for pediatric use. The administration of the drug is facilitated by a device that has a CE mark, ensuring compliance with European safety standards.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the long-term safety and efficacy of **Glepaglutide** in adult patients with **Short Bowel Syndrome**. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed as a single-arm, long-term, phase 3 extension study, following the completion of the EASE SBS 2 trial.

The efficacy of **glepaglutide** in the treatment of Short Bowel Syndrome (SBS) will be assessed through several secondary efficacy endpoints. These endpoints include the reduction in weekly parenteral support (PS) volume from baseline, a reduction of at least 20% in weekly PS volume from baseline, a reduction in the number of days on PS by at least one day per week from baseline, and a complete reduction in weekly PS volume, indicating weaning off PS. These parameters will be measured and collected at specified intervals throughout the 104-week trial period.

Data collection will involve patient-reported outcomes and clinical assessments to evaluate changes from baseline. The analysis will focus on the percentage reduction in PS volume and the number of days on PS, providing a comprehensive overview of the treatment's impact on the patient's dependency on parenteral nutrition. The trial will utilize validated scales and laboratory tests to ensure the accuracy and reliability of the collected data. The efficacy assessments will be conducted in conjunction with safety evaluations to provide a holistic view of the treatment's benefits and risks.