A 104-week, multicenter, open-label, single-arm, phase 3 extension trial investigating the long-term safety and efficacy of Glepaglutide in adult patients with short bowel syndrome (SBS) rolling over from the EASE SBS 2 or 3 trials

The primary objective of this trial is to evaluate the safety and tolerability of glepaglutide 10 mg administered twice weekly in patients with short bowel syndrome. This assessment is clinically relevant for determining the long-term risk-benefit profile of glepaglutide therapy in this patient population requiring chronic intestinal support.

The secondary objective is to evaluate the efficacy of glepaglutide treatment in patients with short bowel syndrome. This evaluation addresses the therapeutic benefit of glepaglutide in managing the clinical manifestations and complications associated with intestinal failure resulting from short bowel syndrome.

This clinical trial enrolled a total of **13 participants** diagnosed with **Short Bowel Syndrome**. The study population included both **male and female subjects** spanning **adult and elderly age groups**. Participants were selected from individuals who had been actively treated in prior glepaglutide studies, specifically those who had completed at least 6 months of glepaglutide treatment in the EASE SBS 2 trial or were actively treated in the EASE SBS 3 trial. The trial involved a **vulnerable population**. Key inclusion criteria required that participants provide signed informed consent and agree to comply with protocol requirements, as well as meet the specified treatment history with glepaglutide from previous trials. The sponsor did not provide information regarding lifestyle considerations such as diet, physical activity, or habits of the study participants.

This is a 104-week, multicenter, open-label, single-arm, **phase 3** extension trial designed to investigate the long-term safety and efficacy of **glepaglutide** in adult patients with **short bowel syndrome**. Participants will be enrolled from two previous trials, EASE SBS 2 or EASE SBS 3, where they have already received treatment with the investigational product. The trial follows an extension design without randomization or blinding, allowing continued evaluation of the therapeutic intervention in this patient population.

The investigational medicinal product is **glepaglutide 20.0 mg/mL**, formulated as a **solution for injection** and administered via **subcutaneous use**. The active substance, glepaglutide, is a synthetic peptide classified as a protein-based therapeutic. The maximum daily dose is **10 mg**, with a treatment period extending up to **104 weeks**. The product will be administered twice weekly throughout the study duration. A device with CE marking will be utilized for product administration.

The primary objective of this trial is to evaluate the safety and tolerability of glepaglutide 10 mg administered twice weekly in patients with short bowel syndrome. The **primary endpoint** consists of treatment-emergent adverse events recorded from baseline (Visit 1) to the safety follow-up visit. The **secondary endpoint** assesses the change in prescribed weekly **parenteral support** volume from baseline to Month 24 or end of treatment. These endpoints will provide comprehensive data on both the safety profile and therapeutic benefit of long-term glepaglutide administration.

Eligible participants must meet specific inclusion criteria. Principal inclusion criteria require that participants have provided **signed informed consent** and agree to comply with protocol requirements. Additionally, participants must be either actively treated and have completed at least 6 months of glepaglutide treatment in the EASE SBS 2 trial, or be actively treated in the EASE SBS 3 trial at the time of enrollment. The trial is expected to commence recruitment on December 28, 2025, with an estimated completion date of December 31, 2028.

Participant involvement will span the full 104-week treatment period, followed by a safety follow-up visit. The baseline visit (Visit 1) will initiate the treatment phase, during which participants will receive continuous glepaglutide therapy. Regular follow-up visits will be conducted throughout the 24-month period to monitor safety parameters, assess efficacy outcomes, and evaluate changes in parenteral support requirements. The end-of-treatment assessment will occur at Month 24, followed by a final safety follow-up visit to capture any delayed adverse events or ongoing safety concerns.

Conditions that may lead to early termination from the study include withdrawal of informed consent, development of unacceptable toxicity or adverse events requiring discontinuation, investigator decision based on safety concerns, or protocol non-compliance. Participants who discontinue treatment prematurely will be encouraged to complete end-of-treatment assessments to ensure comprehensive safety data collection. The trial design allows for thorough evaluation of long-term safety and efficacy in this rare disease population requiring extended parenteral support management.

The experimental medication under investigation is **Glepaglutide** 20.0 mg/mL, a **synthetic peptide** with the sponsor product code ZP1848 20.0 mg/mL. Glepaglutide is classified as a protein-based active substance. The investigational medicinal product is formulated as a **solution for injection** in a ready-to-use pharmaceutical form. The medication is administered via **subcutaneous injection** at a dosage of **10 mg** per administration. The **frequency of administration** is twice weekly (TW), resulting in a **maximum daily dose** of 10 mg and a **maximum total dose** of 10 mg per administration. The **treatment period** extends for **104 weeks**, representing a long-term extension trial for patients with **short bowel syndrome**. The product is supplied by Zealand Pharma and is delivered using a medical device that bears CE marking, specifically designed for subcutaneous administration. The device is intended for use with the medicinal product to ensure accurate dosing and appropriate delivery. Participant compliance monitoring throughout the 104-week treatment period will be essential to evaluate the long-term safety and tolerability profile of glepaglutide in the target patient population.

Efficacy will be assessed through the evaluation of treatment-emergent adverse events (TEAEs) from baseline (Visit 1) to the safety follow-up visit, which serves as the primary endpoint. The secondary endpoint will measure the change in prescribed weekly **parenteral support** volume from baseline to Month 24 or end of treatment. The trial will follow participants over a 104-week treatment period to evaluate the long-term efficacy of **glepaglutide** 10 mg administered twice weekly in patients with **short bowel syndrome**.