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

Phase 3

Completed

• Conditions: Short Bowel Syndrome
• Interventions: Drug: Glepaglutide

• Registration Number: NCT04991311
• Lead Sponsor: Zealand Pharma

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-14
• Study First Submitted QC: 2021-07-27
• Study First Posted: 2021-08-05
• Study Start: 2021-08-10
• Primary Completion: 2023-02-02
• Study Completion: 2023-09-05
• Status Verified: 2024-09
• Results First Submitted: 2024-09-26
• Results First Submitted QC: 2024-09-26
• Last Update Submitted: 2024-09-26
• Results First Posted: 2024-11-22
• Last Update Posted: 2024-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
once-weekly glepaglutide	Glepaglutide	All participants will receive 10 mg of glepaglutide as once-weekly injections under the skin (subcutaneous, s.c.)

Primary Outcome Measures

Name	Time	Method
Change in Absorption of Wet Weight/Fluids	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.

Secondary Outcome Measures

Name	Time	Method
Change in Absorption of Energy	from Week 0 (baseline) to Week 24	Oral intake minus fecal excretion: measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed. Energy absorption was measured by bomb calorimetry.
Change in Absorption of Carbohydrates	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.
Change in Absorption of Lipids	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.
Change in Absorption of Proteins	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.
Change in Absorption of Sodium	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.
Change in Absorption of Potassium	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.
Change in Absorption of Calcium	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.
Change in Absorption of Magnesium	from Week 0 (baseline) to Week 24	Measured by 48-hour metabolic balance studies. The metabolic balance study measured the total intake and output of energy, macronutrients (lipids, carbohydrates, proteins) and micronutrients. The oral diet (food and fluids) was assessed by duplicate meals and liquids. During the metabolic balance study, the patients collected duplicate portions of all fluids and liquids covering 24-hour periods. Likewise, all output (ostomy output, diarrhea and urine production) was collected, quantified and analyzed.
Change in Weekly Parenteral Support (PS) Volume	from Week 0 (baseline) to Week 12	Only for participants with Short Bowel Syndrome with Intestinal Failure (SBS-IF). PS use was recorded in patient diaries throughout the trial, including type and volume used.
Change in Weekly PS Volume	from Week 0 (baseline) to Week 24	Only for participants with SBS-IF. PS use was recorded in patient diaries throughout the trial, including type and volume used.
Change in Weekly PS Carbohydrates	from Week 0 (baseline) to Week 24	Only for participants with SBS-IF. PS use was recorded in patient diaries throughout the trial, including type and volume used.
Change in Weekly PS Lipids	from Week 0 (baseline) to Week 24	Only for participants with SBS-IF. PS use was recorded in patient diaries throughout the trial, including type and volume used.
Change in Weekly PS Proteins	from Week 0 (baseline) to Week 24	Only for participants with SBS-IF. PS use was recorded in patient diaries throughout the trial, including type and volume used.
Change in Weekly PS Sodium	from Week 0 (baseline) to Week 24	Only for participants with SBS-IF. PS use was recorded in patient diaries throughout the trial, including type and volume used.
Change in Weekly PS Potassium	from Week 0 (baseline) to Week 24	Only for participants with SBS-IF. PS use was recorded in patient diaries throughout the trial, including type and volume used.
Change in Weekly PS Magnesium	from Week 0 (baseline) to Week 24	Only for participants with SBS-IF. PS use was recorded in patient diaries throughout the trial, including type and volume used.
Anti-glepaglutide Antibodies	Week 56	Monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56
Reactivity to ZP1848	Week 56	Monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56. Anti-drug antibodies (ADA) positive samples were analyzed for reactivity to ZP1848.
Cross-reactivity to Glucagon-like Peptide-2 (GLP-2)	Week 56	Monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56. ADA positive samples were analyzed for cross-reactivity to glucagon-like peptide-2 (GLP-2).
Glepaglutide Neutralizing Antibodies	Week 56	Monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56

Trial Locations

Locations (1)

Rigshospitalet; 🇩🇰 Copenhagen, Denmark