Trial to Evaluate Efficacy and Safety of Apraglutide in SBS-IF

Study Overview
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Brief Summary
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The primary objective of the trial is the confirmation of the efficacy of apraglutide to evaluate the efficacy of weekly subcutaneous apraglutide in reducing parenteral support dependency.

Detailed Description
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This is an international, multicenter, double-blind, randomized, placebo-controlled, trial to evaluate the efficacy and safety of weekly SC injections of apraglutide in adult subjects with SBS-IF. The active pharmaceutical ingredient is apraglutide, a GLP-2 analogue. The trial consists of a screening phase, a treatment phase of 48 weeks, and a safety follow-up phase. Trial participants will receive, after successful screening, once weekly apraglutide.

Official Title
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A Multicenter, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Apraglutide in Adult Subjects With Short Bowel Syndrome and Intestinal Failure (SBS-IF)

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: apraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Signed informed consent for this trial prior to any trial specific assessment. Male and female subjects with SBS-IF, receiving parenteral support (PS), secondary to surgical resection of the small intestine with either stoma or colon-in-continuity (CIC). Subject must require PS at least 3 days per work and be considered stable. No restorative surgery intended to change PS requirements in the trial period. Age ≥18 years at screening. Exclusion Criteria: Pregnancy or lactation. Major abdominal surgery in the last 6 months prior to screening. History of cancer (including colon carcinoma) or clinically significant lymphoproliferative disease within ≤5 years, except for adequately treated basal cell skin cancer. Evidence of active inflammatory GI conditions in the previous 6 months. Evidence of decompensated heart failure. Evidence of severe renal or hepatic impairment. Any previous use of growth factors such as growth hormone (GH), native GLP-2, GLP-1, or GLP-2 or GLP-1 analogues should be discussed with the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apraglutide SC injections, once weekly<br>Peptide analogue of GLP-2 | Drug: apraglutide<br>* Apraglutide is a peptide analogue of GLP-2 under development for treatment of SBS-IF, which acts as a full agonist at the GLP-2 receptor with in vitro potency and selectivity comparable with native GLP-2.<br>|
| Placebo Comparator: Placebo<br>Placebo for apraglutide, SC injection once weekly | Drug: apraglutide<br>* Apraglutide is a peptide analogue of GLP-2 under development for treatment of SBS-IF, which acts as a full agonist at the GLP-2 receptor with in vitro potency and selectivity comparable with native GLP-2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change from baseline in actual weekly PS volume at Week 24. |  | At week 24 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects who achieve a reduction of at least 1 day per week of PS at Weeks 24 / 48 (CIC only). |  | Weeks 24 and 48 of treatment | 
| Relative change from baseline in actual weekly PS volume at Weeks 12 / 24 / 48 (CIC only). |  | Weeks 12 / 24 / 48 of treatment | 
| Subjects reaching enteral autonomy at Weeks 24 / 48 (CIC only). |  | Weeks 24 / 48 of treatment | 
| At least 20% reduction of PS volume from baseline at Weeks 20 / 24. |  | Weeks 20 / 24 of treatment | 
| Calorie reduction in the PN at Weeks 24. |  | Weeks 24 of treatment | 
| Change from baseline on the Pittsburgh Sleep Quality Inventory (PSQI) at Weeks 24 / 48 (CIC only) |  | Weeks 24 / 48 of treatment | 
| Change from baseline on the Patient Global Impression of Change (PGIC) at Weeks 24 / 48 (CIC only) |  | Weeks 24 / 48 of treatment. | 
| Change from baseline on the Patient Global Impression of Treatment Satisfaction (PGI-TS) at week 24 and 48 (CIC only). |  | Weeks 24 / 48 of treatment | 
| Change from baseline on the Patient Global Impression of Satisfaction with Parenteral Support (PGI-SPS) at Week 24 and 48 (CIC only). |  | Weeks 24 / 48 of treatment | 
| Change from baseline on the Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and 48 (CIC only). |  | Weeks 24 / 48 of treatment | 
| Absorption rate constant (ka) of apraglutide through population PK data analysis |  | Weeks 0 / 24 of treatment | 
| Apparent clearance (CL/F) of apraglutide through population PK data analysis |  | Weeks 0 / 24 of treatment | 
| Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis |  | Weeks 0 / 24 of treatment | 
| At least 40% reduction of PS volume at Weeks 20 and 24 (Stoma only) |  | Weeks 20 / 24 of treatment | 
| Trough plasma concentrations (Ctrough) at every other visit during the prolonged dosing period (CIC only) |  | Weeks 24 / 48 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short Bowel Syndrome, Intestinal Failure, SBS, SBS-IF, GLP-2, Short Bowel Syndrome Intestinal Failure