The Long-term Effect on Intestinal Absorption and Safety of Treatment With Glepaglutide in Patients With Short Bowel Syndrome (EASE SBS 4)

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)

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.

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: Glepaglutide

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: once-weekly glepaglutide; All participants will receive 10 mg of glepaglutide as once-weekly injections under the skin (subcutaneous, s.c.)	Drug: Glepaglutide; Glepaglutide will be delivered in a single-use autoinjector.; Other Names: ZP1848

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zealand Pharma
• Investigators: Study Director: Zealand Pharma, Zealand Pharma

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2021
• Primary Completion (Actual): February 2, 2023
• Study Completion (Actual): September 5, 2023

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): August 5, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Disease; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Syndrome; Short Bowel Syndrome
• Other Study ID Numbers: ZP1848-20060; 2020-005194-27 (EudraCT Number); U1111-1260-2961 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No