Efficacy And Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS) (EASE SBS 1)
Primary Purpose
Short Bowel Syndrome
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
glepaglutide
Placebo
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 activity.
- Diagnosis of SBS defined as remaining small bowel in continuity of estimated less than 200 cm and considered stable with regard to PS need. No restorative surgery planned in the trial period.
- Requiring PS at least 3 days per week and maintains a stable PS volume for at least 2 weeks.
- In case of remnant colon: documented colonoscopy which does not give rise to any safety concerns.
Exclusion Criteria:
- More than 2 SBS-related or PS-related hospitalizations within 6 months prior to Screening. No SBS-related hospitalizations within 30 days prior to randomization.
- Poorly controlled inflammatory bowel disease that is moderately or severely active or fistula interfering with measurements or examinations required in the trial.
- Bowel obstruction.
- Known radiation enteritis or significant villous atrophy.
- 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.
- Clinically significant abnormal ECG.
- Repeated systolic blood pressure measurements > 180 mm Hg.
- Human immunodeficiency virus positive, acute liver disease, or unstable chronic liver disease.
- Any history of colon cancer. History of any other cancers unless disease-free state for at least 5 years.
- Estimated creatinine clearance < 30 mL/min.
- Severe hepatic impairment.
- Use of GLP-1, GLP-2, human growth hormone, somatostatin, or analogs thereof, within 3 months prior to Screening.
- Use of dipeptidyl peptidase (DPP)-4 inhibitors within 3 months prior to Screening.
- Unstable systemic immunosuppressive therapy within 3 months prior to Screening.
- Unstable biological therapy within 6 months prior to Screening.
- Females of childbearing potential, who are pregnant, breast-feeding, intend to become pregnant or are not using highly effective contraceptive methods.
- Previous exposure to glepaglutide.
- Current, or within 30 days prior to Screening, participation in another interventional clinical trial that includes administration of an active compound.
- Any condition or disease or circumstance that in the Investigator's opinion would put the patient at any undue risk, prevent completion of the trial, or interfere with the analysis of the trial results.
Sites / Locations
- Georgetown University Medical Center
- University of Chicago Children's Hospital
- Mayo Clinic College of Medicine
- University of Nebraska Medical Center
- Mount Sinai Hospital
- Cleveland Clinic
- Vanderbilt University Medical Center, Nashville
- UZ Leuven
- The Royal Alexandra Hospital
- Western University
- University Health Network - Toronto General Hospital
- Aalborg University Hospital
- Rigshospitalet
- Hôpital Beaujon
- Centre Hospitalier Lyon-Sud
- Charité - Universitätsmedizin Berlin
- Universitätsklinikum Bonn
- Universitätsklinikum Frankfurt - Med. Klinik I
- Asklepios Kliniken Hamburg GmbH
- Universitätsmedizin Rostock
- UMC Radboud Nijmegen
- Solumed
- Szpital Skawina sp. z o.o. im. Stanley Dudricka
- Wojewodzki Specjalistyczny Szpital im. M. Pirogowa w Lodzi
- St Mark's Hospital
- UCLH Foundation NHS Trust
- Salford Royal NHS Foundation Trust
- University of East Anglia
- University Hospital Southampton NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Glepaglutide SC injections twice weekly
Glepaglutide SC injections once weekly and placebo once weekly
Placebo SC injections twice weekly
Arm Description
Intervention: Glepaglutide
Intervention: Glepaglutide
Intervention: Placebo
Outcomes
Primary Outcome Measures
Change in weekly Parenteral Support (PS) volume
Change in weekly PS volume from baseline
Secondary Outcome Measures
Clinical response in PS volume
Achieving at least 20 percent reduction in weekly PS volume from baseline
Days off PS
Achieving 1 or more days per week off PS
Clinical response in PS volume
Reduction of at least 20 percent in PS volume from baseline
Weaned off PS
Reduction in weekly PS volume of 100 percent (weaned off)
Fluid composite effect
Change in fluid composite effect from baseline
Energy content
Change in energy content of PS from baseline
Days on PS
Change in number of days on PS per week from baseline
Change in PS volume per week
Achieving 40 percent in PS volume from baseline
Patient Global Impression of Change scale (PGIC)
Change PGIC
Safety - Adverse Events
Incidence and type of Adverse Events
Number of patients with clinically significant changes in 12-Lead electrocardiogram (ECG)
Number of patients with clinically significant changes in ECG will be reported
Safety - Changes in blood pressure from baseline
Changes in blood pressure will be reported
Safety - Changes in body temperature from baseline
Changes in body temperature will be reported
Immunogenicity - Occurrence of anti-drug antibodies
Occurrence of antibodies against glepaglutide
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03690206
Brief Title
Efficacy And Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS)
Acronym
EASE SBS 1
Official Title
A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Glepaglutide in Patients With Short Bowel Syndrome (SBS)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
October 4, 2018 (Actual)
Primary Completion Date
July 26, 2022 (Actual)
Study Completion Date
July 26, 2022 (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
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of the trial is to confirm the efficacy of glepaglutide in reducing parenteral support volume in patients with short bowel syndrome.
Glepaglutide is the International Nonproprietary Name and USAN for ZP1848.
Detailed Description
A Phase 3, international, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of glepaglutide subcutaneous (SC) injections in patients with short bowel syndrome (SBS).
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
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
106 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Glepaglutide SC injections twice weekly
Arm Type
Experimental
Arm Description
Intervention: Glepaglutide
Arm Title
Glepaglutide SC injections once weekly and placebo once weekly
Arm Type
Experimental
Arm Description
Intervention: Glepaglutide
Arm Title
Placebo SC injections twice weekly
Arm Type
Placebo Comparator
Arm Description
Intervention: Placebo
Intervention Type
Drug
Intervention Name(s)
glepaglutide
Other Intervention Name(s)
ZP1848
Intervention Description
Glucagon-Like Peptide-2 (GLP-2) analog
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for glepaglutide
Primary Outcome Measure Information:
Title
Change in weekly Parenteral Support (PS) volume
Description
Change in weekly PS volume from baseline
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Clinical response in PS volume
Description
Achieving at least 20 percent reduction in weekly PS volume from baseline
Time Frame
20 and 24 weeks
Title
Days off PS
Description
Achieving 1 or more days per week off PS
Time Frame
24 weeks
Title
Clinical response in PS volume
Description
Reduction of at least 20 percent in PS volume from baseline
Time Frame
12 and 24 weeks
Title
Weaned off PS
Description
Reduction in weekly PS volume of 100 percent (weaned off)
Time Frame
24 weeks
Title
Fluid composite effect
Description
Change in fluid composite effect from baseline
Time Frame
24 weeks
Title
Energy content
Description
Change in energy content of PS from baseline
Time Frame
24 weeks
Title
Days on PS
Description
Change in number of days on PS per week from baseline
Time Frame
24 weeks
Title
Change in PS volume per week
Description
Achieving 40 percent in PS volume from baseline
Time Frame
20 and 24 weeks
Title
Patient Global Impression of Change scale (PGIC)
Description
Change PGIC
Time Frame
24 weeks
Title
Safety - Adverse Events
Description
Incidence and type of Adverse Events
Time Frame
28 weeks
Title
Number of patients with clinically significant changes in 12-Lead electrocardiogram (ECG)
Description
Number of patients with clinically significant changes in ECG will be reported
Time Frame
28 weeks
Title
Safety - Changes in blood pressure from baseline
Description
Changes in blood pressure will be reported
Time Frame
28 weeks
Title
Safety - Changes in body temperature from baseline
Description
Changes in body temperature will be reported
Time Frame
28 weeks
Title
Immunogenicity - Occurrence of anti-drug antibodies
Description
Occurrence of antibodies against glepaglutide
Time Frame
28 weeks
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 activity.
Diagnosis of SBS defined as remaining small bowel in continuity of estimated less than 200 cm and considered stable with regard to PS need. No restorative surgery planned in the trial period.
Requiring PS at least 3 days per week and maintains a stable PS volume for at least 2 weeks.
In case of remnant colon: documented colonoscopy which does not give rise to any safety concerns.
Exclusion Criteria:
More than 2 SBS-related or PS-related hospitalizations within 6 months prior to Screening. No SBS-related hospitalizations within 30 days prior to randomization.
Poorly controlled inflammatory bowel disease that is moderately or severely active or fistula interfering with measurements or examinations required in the trial.
Bowel obstruction.
Known radiation enteritis or significant villous atrophy.
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.
Clinically significant abnormal ECG.
Repeated systolic blood pressure measurements > 180 mm Hg.
Human immunodeficiency virus positive, acute liver disease, or unstable chronic liver disease.
Any history of colon cancer. History of any other cancers unless disease-free state for at least 5 years.
Estimated creatinine clearance < 30 mL/min.
Severe hepatic impairment.
Use of GLP-1, GLP-2, human growth hormone, somatostatin, or analogs thereof, within 3 months prior to Screening.
Use of dipeptidyl peptidase (DPP)-4 inhibitors within 3 months prior to Screening.
Unstable systemic immunosuppressive therapy within 3 months prior to Screening.
Unstable biological therapy within 6 months prior to Screening.
Females of childbearing potential, who are pregnant, breast-feeding, intend to become pregnant or are not using highly effective contraceptive methods.
Previous exposure to glepaglutide.
Current, or within 30 days prior to Screening, participation in another interventional clinical trial that includes administration of an active compound.
Any condition or disease or circumstance that in the Investigator's opinion would put the patient at any undue risk, prevent completion of the trial, or interfere with the analysis of the trial results.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Zealand Pharma
Official's Role
Study Director
Facility Information:
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Chicago Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Mayo Clinic College of Medicine
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-3285
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Vanderbilt University Medical Center, Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
68198-3285
Country
United States
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
The Royal Alexandra Hospital
City
Edmonton
Country
Canada
Facility Name
Western University
City
London
ZIP/Postal Code
N6A 4V2
Country
Canada
Facility Name
University Health Network - Toronto General Hospital
City
Toronto
Country
Canada
Facility Name
Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
Country
Denmark
Facility Name
Hôpital Beaujon
City
Clichy
Country
France
Facility Name
Centre Hospitalier Lyon-Sud
City
Pierre-Bénite
Country
France
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
Universitätsklinikum Bonn
City
Bonn
Country
Germany
Facility Name
Universitätsklinikum Frankfurt - Med. Klinik I
City
Frankfurt
Country
Germany
Facility Name
Asklepios Kliniken Hamburg GmbH
City
Hamburg
Country
Germany
Facility Name
Universitätsmedizin Rostock
City
Rostock
Country
Germany
Facility Name
UMC Radboud Nijmegen
City
Nijmegen
Country
Netherlands
Facility Name
Solumed
City
Poznań
Country
Poland
Facility Name
Szpital Skawina sp. z o.o. im. Stanley Dudricka
City
Skawina
Country
Poland
Facility Name
Wojewodzki Specjalistyczny Szpital im. M. Pirogowa w Lodzi
City
Łódź
Country
Poland
Facility Name
St Mark's Hospital
City
Harrow
Country
United Kingdom
Facility Name
UCLH Foundation NHS Trust
City
London
Country
United Kingdom
Facility Name
Salford Royal NHS Foundation Trust
City
Manchester
Country
United Kingdom
Facility Name
University of East Anglia
City
Norwich
Country
United Kingdom
Facility Name
University Hospital Southampton NHS Foundation Trust
City
Southampton
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Efficacy And Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS)
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