Back to resultsThe Long-term Effect on Intestinal Absorption and Safety of Treatment With Glepaglutide in Patients With Short Bowel Syndrome (EASE SBS 4)
Primary Purpose
Short Bowel Syndrome
Status
Completed
Phase
Phase 3
Locations
Denmark
Study Type
Interventional
Intervention
Glepaglutide
Sponsored by
About this trial
This is an interventional treatment trial for Short Bowel Syndrome
Eligibility Criteria
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
Sites / Locations
- Rigshospitalet
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
once-weekly glepaglutide
Arm Description
All participants will receive 10 mg of glepaglutide as once-weekly injections under the skin (subcutaneous, s.c.)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Anti-glepaglutide antibodies
Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 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.
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).
Glepaglutide neutralizing antibodies
Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04991311
Brief Title
The Long-term Effect on Intestinal Absorption and Safety of Treatment With Glepaglutide in Patients With Short Bowel Syndrome
Acronym
EASE SBS 4
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
August 10, 2021 (Actual)
Primary Completion Date
February 2, 2023 (Actual)
Study Completion Date
September 5, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand Pharma
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Short Bowel Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
once-weekly glepaglutide
Arm Type
Experimental
Arm Description
All participants will receive 10 mg of glepaglutide as once-weekly injections under the skin (subcutaneous, s.c.)
Intervention Type
Drug
Intervention Name(s)
Glepaglutide
Other Intervention Name(s)
ZP1848
Intervention Description
Glepaglutide will be delivered in a single-use autoinjector.
Primary Outcome Measure Information:
Title
Change in absorption of wet weight/fluids
Description
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.
Time Frame
Week 0, Week 24
Secondary Outcome Measure Information:
Title
Change in absorption of energy
Description
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
Time Frame
Week 0, Week 24
Title
Change in absorption of carbohydrates
Description
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.
Time Frame
Week 0, Week 24
Title
Change in absorption of lipids
Description
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.
Time Frame
Week 0, Week 24
Title
Change in absorption of proteins
Description
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.
Time Frame
Week 0, Week 24
Title
Change in absorption of sodium
Description
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.
Time Frame
Week 0, Week 24
Title
Change in absorption of potassium
Description
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.
Time Frame
Week 0, Week 24
Title
Change in absorption of calcium
Description
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.
Time Frame
Week 0, Week 24
Title
Change in absorption of magnesium
Description
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.
Time Frame
Week 0, Week 24
Title
Change in weekly parenteral support (PS) volume
Description
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.
Time Frame
Week 0, Week 12
Title
Change in weekly PS volume
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 24
Title
Change in weekly PS carbohydrates
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 12
Title
Change in weekly PS carbohydrates
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 24
Title
Change in weekly PS lipids
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 12
Title
Change in weekly PS lipids
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 24
Title
Change in weekly PS proteins
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 12
Title
Change in weekly PS proteins
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 24
Title
Change in weekly PS sodium
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 12
Title
Change in weekly PS sodium
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 24
Title
Change in weekly PS potassium
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 12
Title
Change in weekly PS potassium
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 24
Title
Change in weekly PS magnesium
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 12
Title
Change in weekly PS magnesium
Description
Only for participants with SBS-IF. PS use will be recorded in patient diaries throughout the trial, including type and volume used.
Time Frame
Week 0, Week 24
Title
Anti-glepaglutide antibodies
Description
Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56
Time Frame
Week 56
Title
Reactivity to ZP1848
Description
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.
Time Frame
Week 56
Title
Cross-reactivity to glucagon-like peptide-2 (GLP-2)
Description
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).
Time Frame
Week 56
Title
Glepaglutide neutralizing antibodies
Description
Will be monitored throughout the trial at baseline (Week 0) and weeks 4, 12, 24, 52 and 56
Time Frame
Week 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zealand Pharma
Organizational Affiliation
Zealand Pharma
Official's Role
Study Director
Facility Information:
Facility Name
Rigshospitalet
City
Copenhagen
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Long-term Effect on Intestinal Absorption and Safety of Treatment With Glepaglutide in Patients With Short Bowel Syndrome
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