Metabolic Balance Study of Apraglutide in Patients With SBS-IF and Colon-in-Continuity

Study Overview
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Brief Summary
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The primary objective of the trial is to evaluate the safety of apraglutide in adult subjects with SBS-IF and CIC.

Detailed Description
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This is an international, multicenter trial to evaluate the safety of apraglutide in adult subjects with SBS-IF and CIC. The active pharmaceutical ingredient is apraglutide, an investigational GLP-2 analogue. The trial consists of an evaluation period of 52 weeks.

Official Title
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A Multicenter, Open-label, Metabolic Balance Study to Evaluate the Effects of Apraglutide on Intestinal Absorption in Adult Subjects With Short Bowel Syndrome, Intestinal Failure (SBS-IF), and Colon-in-Continuity (CIC)

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 and CIC, receiving parenteral support (PS), secondary to surgical resection of the small intestine with <200 cm from duodenojejunal flexure. Subject must require PS at least 2 days per week 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. Body mass index equal or higher than 30 kg/m2 at the time of screening. Major abdominal surgery in the last 6 months prior to screening.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


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 synthetic 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 |
| --- | --- | --- |
| To evaluate the safety and tolerability of apraglutide | Assessed by: Adverse events (AEs; system organ class, frequency and severity) Adverse events of special interest (AESIs): Injection site reaction Gastrointestinal obstruction Gallbladder, biliary and pancreatic disease Fluid overload Colorectal polyps Malignancies Clinical chemistry, hematology, hemostasis, anti-drug antibodies (ADA), and urine analysis | From baseline to week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change from baseline in actual weekly PS volume |  | Weeks 24 and 52 | 
| Absolute change from baseline in actual weekly PS volume |  | Weeks 24 and 52 | 
| Subjects who achieve a reduction of at least 1 day per week of PS |  | From Baseline at weeks 24 and 52 | 
| Clinical responders (20% reduction of PS volume from baseline) |  | Weeks 24 and 52 | 
| Subjects reaching enteral autonomy as assessed by the need or reduction of parenteral support requirements. |  | Weeks 24 and 52 | 
| Energy reduction in the Parenteral Nutrition as assessed by parenteral support calorie content | Units: Cal/week | From Baseline at weeks 24 and 52 | 
| Change in absolute energy absorption assessed by the difference between oral intake and excretion | Assessed by bomb calorimetry Units: Cal/gr | From Baseline to week 48 | 
| Relative change in absorption of energy derived as the difference between oral intake and excretion. | Assessed by bomb calorimetry | From Baseline at week 4 and at week 48 | 
| Relative change in absorption of carbohydrate derived as the difference between oral intake and excretion | Assessed by Englyst's method | From Baseline at week 4 and at week 48 | 
| Relative change in absorption of nitrogen derived as the difference between oral intake and excretion | Assessed by Kjeldahl's method | From Baseline at week 4 and at week 48 | 
| Relative change in absorption of lipid derived as the difference between oral intake and excretion | Assessed by modified Van de Kamer titration technique | From Baseline at week 4 and at week 48 | 
| Change in absolute absorption of energy over metabolic balance periods to assess changes in nutrient absorption of intestinal output | Assessed by bomb calorimetry Units: Cal/day | From Baseline at week 4 and at week 48 | 
| Change in absolute absorption of carbohydrate, over metabolic balance periods | Assessed by Englyst's method Units: kJ/day | From Baseline at week 4 and at week 48 | 
| Change in absolute absorption of nitrogen, over metabolic balance periods | Assessed by Kjeldahl's method Units: kJ/day | From Baseline at week 4 and at week 48 | 
| Change in absolute absorption of lipid, over metabolic balance periods | Assessed by modified Van de Kamer titration technique Units: kJ/day | From Baseline at week 4 and at week 48 | 
| Changes in urine output over metabolic balance periods. | Units: L/day | From Baseline at weeks 4 and 48 | 
| Changes in urinary sodium as assessed by flame photometry | Units: mmol/day | From Baseline at weeks 4 and 48 | 
| Changes in urinary potassium as assessed by flame photometry | Units: mmol/day | From Baseline at weeks 4 and 48 | 
| Changes in urinary calcium as assessed by atomic absorption spectrometry | Units: mmol/day | From Baseline at weeks 4 and 48 | 
| Changes in urinary magnesium as assessed by atomic absorption spectrometry | Units: mmol/day | From Baseline at weeks 4 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intestinal Failure, SBS, SBS-IF, CIC, Colon-in-Continuity