The Long-term Effect on Intestinal Absorption and Safety of Treatment With Glepaglutide in Patients With Short Bowel Syndrome

Study Overview
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Brief Summary
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The purpose of this trial is to investigate the long-term effect of glepaglutide on the intestinal absorption, nutritional status of participants with Short Bowel Syndrome (SBS). The trial will also investigate whether glepaglutide is safe during long-term use. All participants in the trial will receive glepaglutide injections. Participants will have 14 visits with the study doctor. At 2 of these, participants will spend 48 hours at the trial site, one visit at the start of the trial and one after 24 weeks of treatment with glepaglutide. At all visits, participants will meet with trial staff and will have blood tests along with other clinical checks and tests done. Participants will be asked about their health and medical history.

Official Title
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A Single-Center Phase 3b Trial Investigating the Long-term Effect on Intestinal Absorption, Nutritional Status and Long-Term Safety of Treatment With Glepaglutide in Patients With Short Bowel Syndrome (SBS)

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Glepaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial Age greater than or equal to 18 years and less than or equal to 90 years at screening Stable condition of SBS either with intestinal failure (SBS-IF) or intestinal insufficiency. For patients with SBS-IF, a stable condition is defined as less than 25 percent change in parenteral support (PS) volume or energy content for 4 weeks prior to screening. Stable body weight (less than 5 percent change in weight in the 3 months prior to screening) Wet weight of fecal excretion greater than or equal to 1500 grams per day demonstrated during a hospital stay prior to screening Exclusion Criteria: More than 2 SBS-related or PS-related hospitalizations (e.g., catheter-related bacteremia/sepsis, bowel obstruction, severe water-electrolytes disturbances, etc.) within 6 months prior to screening Poorly controlled inflammatory bowel disease (IBD) that is moderately or severely active or fistula interfering with measurements or examinations required in the trial Current bowel obstruction Known radiation enteritis or significant villous atrophy, e.g., due to active celiac disease Cardiac disease defined as: decompensated heart failure (New York Heart Association [NYHA] Class III-IV), unstable angina pectoris, and/or myocardial infarction within the last 6 months prior to screening Any history of colon cancer. History of any other cancers (except margin-free resected cutaneous basal or squamous cell carcinoma or adequately treated in situ cervical cancer) unless disease-free state for at least 5 years Use of glucagon-like peptide-1 (GLP-1), GLP-2, human growth hormone (HGH), somatostatin, or analogs thereof, within 3 months prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: once-weekly glepaglutide<br>All participants will receive 10 mg of glepaglutide as once-weekly injections under the skin (subcutaneous, s.c.) | Drug: Glepaglutide<br>* Glepaglutide will be delivered in a single-use autoinjector.<br>* Other names: ZP1848;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in absorption of wet weight/fluids | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in absorption of energy | Oral intake minus fecal excretion. Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed.Energy absorption is measured by bomb calorimetry | Week 0, Week 24 | 
| Change in absorption of carbohydrates | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 
| Change in absorption of lipids | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 
| Change in absorption of proteins | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 
| Change in absorption of sodium | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 
| Change in absorption of potassium | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 
| Change in absorption of calcium | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 
| Change in absorption of magnesium | Measured by 48-hour metabolic balance studies. The metabolic balance study measures the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) are assessed by duplicate meals and liquids. During the metabolic balance study, the patients will collect duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) will be collected, quantified and analyzed. | Week 0, Week 24 | 
| Change in weekly parenteral support (PS) volume | Only for participants with Short Bowel Syndrome with Intestinal Failure (SBS-IF). PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 12 | 
| Change in weekly PS volume | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 24 | 
| Change in weekly PS carbohydrates | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 12 | 
| Change in weekly PS carbohydrates | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 24 | 
| Change in weekly PS lipids | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 12 | 
| Change in weekly PS lipids | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 24 | 
| Change in weekly PS proteins | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 12 | 
| Change in weekly PS proteins | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 24 | 
| Change in weekly PS sodium | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 12 | 
| Change in weekly PS sodium | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 24 | 
| Change in weekly PS potassium | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 12 | 
| Change in weekly PS potassium | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 24 | 
| Change in weekly PS magnesium | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 12 | 
| Change in weekly PS magnesium | Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used. | Week 0, Week 24 | 
| Anti-glepaglutide antibodies | Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56 | Week 56 | 
| Reactivity to ZP1848 | Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56. Anti-drug antibodies (ADA) positive samples will be analyzed for reactivity to ZP1848. | Week 56 | 
| Cross-reactivity to glucagon-like peptide-2 (GLP-2) | Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56. ADA positive samples will be analyzed for cross-reactivity to glucagon-like peptide-2 (GLP-2). | Week 56 | 
| Glepaglutide neutralizing antibodies | Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56 | Week 56 |