A Study to Investigate the Efficacy and Safety of Apraglutide Compared With Placebo in Adult Participants With Short Bowel Syndrome Associated With Intestinal Failure (SBS-IF)

This Phase 3 placebo-controlled study is planned to further investigate the efficacy, safety, and tolerability of apraglutide in the overall SBS-IF (short bowel syndrome associated with intestinal failure) population during 24 weeks of study treatment. It is expected that approximately 124 participants will be randomized worldwide to either apraglutide or placebo in a 1:1 ratio in this trial.

Inclusion Criteria: * Participant must be ≥18 years of age, at the time of signing the informed consent. * Male and female participants with SBS-IF, receiving PS secondary to surgical resection of the small intestine with residual length ≥10 cm to \1.5 for a person not using anticoagulant drug and INR \>3 for a person on anticoagulant therapy such as warfarin; (c.) ALT or AST \>3 × ULN and clinical signs of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia; (d.) Participants with serum conjugated bilirubin \>34 μmol/L during 2 consecutive measurements. * Use of diuretics, anti-diarrheals, and other common concomitant medications used in SBS-IF if dosing is not stable within 14 days prior to randomization. * New drug treatment other than biologic therapies, or a change to the dose or dosing interval of an existing drug treatment other than a biologic, within 1 month prior to randomization. In cases of weight loss or weight gain, dose adjustments that enable the same drug unit/kg dosing (eg, mg/kg) for weight-based dosing are permitted within 1 month prior to randomization after discussion with the medical monitor and proper documentation. * New biologic therapy or changes to dose or dosing interval of existing biologic therapy within 3 months prior to Screening, unless the dose adjustment was due to a change in weight and maintained the same drug-unit/kg (eg, mg/kg) weight-based dosing. Switching from a reference biologic product to a biosimilar, while maintaining the same dose and dosing interval, is permitted outside the 3 months prior to the screening window and/or during the study. * Use of dipeptidyl peptidase-4 inhibitors within 3 months prior to Screening. * At least 2 weeks of treatment with growth factors, such as growth hormone, glutamine, native GLP-2, GLP-1, short acting GLP-2 analogs (eg, teduglutide) or GLP-1 analogs within 3 months before Screening; or treatment with longer acting experimental GLP-2 analogs in the previous 6 months before Screening. Note: Prior discontinuation of GLP-2 analog treatment due to safety concerns or lack of efficacy is an exclusion criterion regardless of wash-out period. For prior discontinuation due to intolerance, the patient may be eligible based on discussion with the medical monitor. The nature of the intolerance must be clearly documented and discussed with the medical monitor. * Citrulline supplements within less than 30 days prior to Screening. * Prior use of apraglutide, or prior randomization in this study. Note: Randomization to placebo in a prior study of apraglutide is not an exclusion criterion. * Known or suspected hypersensitivity to GLP-1 or GLP-2 analogs or any apraglutide excipients. * Known antidrug antibodies (ADAs) against GLP-1 or GLP-2 analogs. * Participation in another interventional clinical study in the last 3 months before screening and during this study (studies with catheter locks or observational studies, which are not a burden on the participant and do not interfere with the participation in this study, are allowed after discussion with the medical monitor). * Incapable of understanding or unwilling to adhere to the study visit schedules and/or other protocol requirements. * Inability to prepare and/or administer the dose of the study intervention or inability to have the dose prepared and/or administered by an appropriately trained care provider. * Any condition, underlying disease, or circumstance, including psychosocial or environmental that, in the opinion of the investigator, could reduce the participant's adherence with the study visit schedule, dosing regimen, or other study requirements. * Participant is directly or indirectly involved in the conduct and administration of this study as an investigator, subinvestigator, study coordinator, study staff member, or employee of the sponsor; or the participant is a direct relative of an individual involved in the study.