Evaluation of Long-term Safety and Tolerability of Apraglutide in Patients with Short Bowel Syndrome-Intestinal Failure

The primary objective of this study is to assess the long-term **safety** and tolerability of **apraglutide** in subjects with short bowel syndrome with intestinal failure (SBS-IF). This is clinically relevant as it aims to ensure that apraglutide, a novel therapeutic agent, can be safely administered over an extended period, providing a potential treatment option for patients with SBS-IF, a condition characterized by malabsorption and nutritional deficiencies due to insufficient intestinal surface area.

Secondary objectives include evaluating markers indicative of the clinical effects of apraglutide. This will help in understanding the therapeutic impact of apraglutide on patients with SBS-IF, potentially guiding future treatment protocols and improving patient outcomes.

The clinical trial involves a total of **51 participants** diagnosed with **short bowel syndrome** secondary to surgical resection of the small intestine. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, indicating a broad adult age group. Participants were selected based on their previous involvement in parent trials TA799-007 or TA799-013, ensuring they did not meet any stopping criteria and had completed a significant portion of the planned doses. The trial includes individuals with a **chronic intestinal failure** (CIC) or stoma, and those who were unable to complete the parent trials due to non-drug-related logistical reasons may also be eligible. Lifestyle considerations such as diet and physical activity are not specified, but participants must be able to provide informed consent and adhere to the trial protocol. The trial population is considered vulnerable, and both genders are required to adhere to strict contraceptive measures during and after the trial period. The sponsor has not provided additional information regarding specific lifestyle factors or health status beyond the inclusion criteria.

The clinical trial is designed to evaluate the long-term safety and tolerability of **apraglutide** in subjects with short bowel syndrome. This is an open-label extension trial, which means that both the researchers and participants know which treatment is being administered. The trial is expected to run until October 2027, with recruitment having started in June 2021. Participants will be involved in the study for a maximum treatment period of 208 weeks, during which they will receive apraglutide via subcutaneous injection. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess overall outcomes.

Participants eligible for the trial are those who have previously been involved in parent trials TA799-007 or TA799-013 and have met specific criteria, such as completing a minimum of 70% of planned doses in the parent trial. The primary endpoints of the study include monitoring adverse events, clinically relevant changes in vital signs, and laboratory assessments. Secondary endpoints focus on changes from baseline in parenteral support volume, frequency, and composition, as well as quality of life measures.

Participants are expected to adhere to the trial protocol, including the use of effective contraception methods for women of childbearing potential and their male partners. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or failure to comply with the study protocol. The trial aims to provide comprehensive data on the safety profile of apraglutide, contributing to the understanding of its long-term use in managing short bowel syndrome.

The clinical trial involves the administration of **Apraglutide**, a novel 33 amino acid synthetic peptide analogue of glucagon-like peptide-2 (GLP-2). Apraglutide is provided in the form of a **powder and solvent for solution for injection** in a pre-filled syringe. The route of administration is **subcutaneous use**. The maximum daily dose of Apraglutide is 5 mg, with a total maximum dose of 1040 mg over a treatment period of 208 days. The pharmaceutical form is designed to ensure precise dosing and ease of administration. Apraglutide is not a pediatric formulation and is classified as an orphan drug, indicating its use in rare conditions.

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 tolerability of Apraglutide in subjects with Short Bowel Syndrome with Intestinal Failure (SBS-IF). Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol. The trial aims to provide comprehensive data on the safety profile of Apraglutide when used over an extended period.

Efficacy in the clinical trial evaluating the long-term safety of Apraglutide in patients with Short Bowel Syndrome with Intestinal Failure (SBS-IF) will be assessed using both primary and secondary endpoints. The primary endpoints focus on safety parameters, including the frequency and severity of **adverse events** (AEs), the occurrence of clinically relevant AEs of special interest such as injection site reactions, gastrointestinal obstructions, and changes in clinical chemistry, hematology, and vital signs. Additionally, changes in electrocardiogram (ECG) intervals and rhythm will be monitored.

Secondary endpoints will assess efficacy through various measures of patient health and quality of life. These include changes from baseline in parenteral support (PS) volume, frequency, composition, and infusion time at specified intervals (Weeks 52, 104, 152, and 208). The percentage of subjects achieving enteral autonomy by these timepoints will also be evaluated. Patient-reported outcomes will be collected using validated instruments such as the Pittsburgh Sleep Quality Index (PSQI), Patient Global Impression of Change (PGIC), and the Short Form (36) Health Survey (SF-36), among others. These assessments will occur at the same specified intervals to provide a comprehensive evaluation of the treatment's impact over time.