Testing Apraglutide against a placebo for short bowel syndrome (SBS)

Exclusion

• −Known or suspected hypersensitivity to GLP-1 or GLP-2 analogs or any apraglutide excipients.
• −Positive results for HIV, hepatitis A, B, and/or C tests at the Screening VisitScreeningThe checks done before joining, to see whether a study fits.Read more →. Note: Participants recovered from hepatitis B or C can be enrolledEnrolmentThe number of participants a study plans to include, or has included.Read more →, ie, they have markers of the infection, but the viral load is undetectable. Participants with evidence of an acute or chronically active hepatitis B or C infection should be excluded. If a participant has a positive hepatitis A immunoglobulin M test, this would indicate an acute infection and the participant is ineligible, but they may be eligible for rescreening after recovery. Participants with positive HIV test results and undetectable viral loads may be rescreened (in case the initial test was a false positive).
• −Ultra-short gut (residual length \<10 cm from duodeno-jejunal flexure).
• −A history of clinically significant intestinal adhesions increasing the risk of GI obstruction and/or GI contrast study(ies) of remaining small bowel suggesting subacute intestinal obstruction or mild stricture within 6 months prior to Screening.
• −Constipation that is not adequately managed by dietary recommendations, laxatives, or cathartic medications.
• −Active or untreated enterocutaneous fistula.
• −History of cancer (including colon carcinoma) or clinically significant lymphoproliferative disease within ≤5 years, except for adequately treated basal cell skin cancer.
• −Diagnosis of any variant of familial adenomatous polyposis or comparable polyposis syndrome.
• −Active inflammatory bowel disease or any other acute or chronic related underlying medical condition that, in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, would limit the participant's ability to complete or participate in the study, or confound study results. Discussion with the medical monitor is required.
• −Sepsis experienced within the previous 2 months prior to or during Screening; or a central venous catheter infection requiring the use of systemic antibiotics within 30 days prior to or during Screening, with the exception of systemic antibiotics administered for \<72 hours while awaiting the results of pending blood culture(s) that turn out negative (ie, \<72 hours empiric systemic antibiotics while ruling out a central venous catheter infection is allowed as long as the culture turns out negative).
• −Decompensated heart failure (New York Heart Association class III-IV) and/or known coronary heart disease defined as unstable angina pectoris and/or myocardial infarction within the previous 6 months prior to Screening.
• −History of alcohol or drug abuse within the previous 12 months prior to Screening that, in the opinion of the investigator, could interfere with study participation, compliance, and safety of participants.
• −Child-Pugh scale Class C for liver disease.
• −Evidence of chronic renal disease as demonstrated by inadequate renal function, which is defined as estimated glomerular filtration rate \<20 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology formula).
• −Clinically significant concurrent illness (eg, uncontrolled hypertension, pancreatic or gallbladder disease) or finding on physical examination or clinical laboratory test after signing the ICFInformed consentThe process of being told what taking part involves, then choosing freely.Read more → but before receiving the first dose of IMP. Note: The investigator will determine if a finding is clinically significant. The investigator will consider whether the finding 1) could prevent the participant from performing any study procedure or assessment, 2) represents a condition that would be exclusionary, 3) could represent a safety concern if the participant participated in the study, or 4) could confound any study assessment.
• −Elevated liver enzymes during the screening period: (a.) ALT or AST \>5 × upper limit of normal (ULN); (b.) ALT or AST \>3 × ULN and total bilirubin (TBL) \>2 × ULN or international normalized ratio (INR) \>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 randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →.
• −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 criterionExclusion criteriaThe things that would prevent someone from taking part.Read more → regardless of wash-outWashout periodA gap with no treatment, so the previous one clears your system.Read more → 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 placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → in a prior study of apraglutide is not an exclusion criterion.
• −Known antidrug antibodies (ADAs) against GLP-1 or GLP-2 analogs.
• −Participation in another interventionalInterventional studyA study where participants are given something to see what happens.Read more → clinical study in the last 3 months before screening and during this study (studies with catheter locks or observationalObservational studyA study that watches what happens without assigning any treatment.Read more → 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 protocolProtocolThe detailed plan a study must follow.Read more → 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 sponsorSponsorThe organisation responsible for the study overall.Read more →; or the participant is a direct relative of an individual involved in the study.
• −Pregnancy and/or lactation and/or plans to become pregnant or to breastfeed.
• −Major abdominal surgery (more than 10% intestinal resection or surgery that changes anatomy group) in the last 6 months prior to Screening Visit. Surgery for feeding tube placement and cholecystectomy allowed, after discussion with medical monitor and appropriate documentation. Any planned surgical procedures during the study duration must be discussed with the medical monitor prior to enrollment, with appropriate documentation of approval of eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more →, if applicable.
• −Radiation enteritis, scleroderma, or residual evidence of intestinal dysmotility, including pseudo-obstruction and Hirschsprung's disease, coeliac disease, refractory or tropical sprue.