Efficacy And Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS) (EASE SBS 1)

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)

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.

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: glepaglutide; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • UZ Leuven
• Canada
  • Edmonton, Canada
    • The Royal Alexandra Hospital
  • London, Canada, N6A 4V2
    • Western University
  • Toronto, Canada
    • University Health Network - Toronto General Hospital
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
  • Copenhagen, Denmark
    • Rigshospitalet
• France
  • Clichy, France
    • Hopital Beaujon
  • Pierre-Bénite, France
    • Centre hospitalier Lyon-Sud
• Germany
  • Berlin, Germany
    • Charité - Universitätsmedizin Berlin
  • Bonn, Germany
    • Universitatsklinikum Bonn
  • Frankfurt, Germany
    • Universitätsklinikum Frankfurt - Med. Klinik I
  • Hamburg, Germany
    • Asklepios Kliniken Hamburg GmbH
  • Rostock, Germany
    • Universitätsmedizin Rostock
• Netherlands
  • Nijmegen, Netherlands
    • UMC Radboud Nijmegen
• Poland
  • Poznań, Poland
    • SOLUMED
  • Skawina, Poland
    • Szpital Skawina sp. z o.o. im. Stanley Dudricka
  • Łódź, Poland
    • Wojewodzki Specjalistyczny Szpital im. M. Pirogowa w Lodzi
• United Kingdom
  • Harrow, United Kingdom
    • St Mark's Hospital
  • London, United Kingdom
    • UCLH Foundation NHS Trust
  • Manchester, United Kingdom
    • Salford Royal NHS Foundation Trust
  • Norwich, United Kingdom
    • University of East Anglia
  • Southampton, United Kingdom
    • University Hospital Southampton NHS Foundation Trust
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Children's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic College of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198-3285
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 68198-3285
      • Vanderbilt University Medical Center, Nashville

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glepaglutide SC injections twice weekly; Intervention: Glepaglutide	Drug: glepaglutide; Glucagon-Like Peptide-2 (GLP-2) analog; Other Names: ZP1848
Experimental: Glepaglutide SC injections once weekly and placebo once weekly; Intervention: Glepaglutide	Drug: glepaglutide; Glucagon-Like Peptide-2 (GLP-2) analog; Other Names: ZP1848; Drug: Placebo; Placebo for glepaglutide
Placebo Comparator: Placebo SC injections twice weekly; Intervention: Placebo	Drug: Placebo; Placebo for glepaglutide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weekly Parenteral Support (PS) Volume	Change in weekly PS volume from baseline to Week 24. Baseline actual weekly PS volume was defined as the actual PS volume derived from a valid 7-day period prior to visit 1 (Day 1), i.e. during the stabilization phase. The actual weekly PS volume at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 was derived as the actual weekly PS volume received during the valid 7-day period prior to the visit. The source for the derivation was the PS volumes recorded by the patients in the eDiary.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days on PS	Change in number of days on PS per week from baseline	24 weeks
Clinical Response in PS Volume	Clinical response, defined as at least 20% reduction in actual weekly PS volume from baseline to both Weeks 20 and 24.	20 and 24 weeks
Days Off PS	Achieving 1 or more days per week off PS	24 weeks
Clinical Response in PS Volume	Reduction of at least 20 percent in PS volume from baseline to both 12 and 24 weeks.	12 and 24 weeks
Weaned Off PS	Reduction in weekly PS volume of 100 percent (weaned off)	24 weeks
Energy Content	Change in weekly energy content of PS from baseline	24 weeks
Change in PS Volume Per Week	Achieving reduction of at least 40 percent in PS volume from baseline to both 20 and 24 weeks	20 and 24 weeks
Patient Global Impression of Change Scale (PGIC)	Patient Global Impression of Change scale (PGIC) improvement at Weeks 4, 12, 20, and 24 PGIC improvement was defined as responding "Very Much Improved" or "Much Improved" on a 7-point Likert Scale. Improvement between each glepaglutide treatment regimen compared to placebo was tested by week, using the CMH test adjusted for the stratification factor. Improvement between each glepaglutide treatment regimen versus placebo was tested using collapsed categories of Improvement, No Change, and Worsening, where Improvement is defined as a response of "Very Much Improved" or "Much Improved" or "Minimally Improved", and No Change is defined as the response of "No Change", and Worsening is defined as a response of "Minimally Worse" or "Much Worse" or "Very Much Worse". Improvement using collapsed categories between each glepaglutide treatment regimen compared to placebo was tested by week using a Mantel-Haenszel chi-squared test for ordered categories.	24 weeks
Safety - Adverse Events	Incidence and type of Adverse Events over an average of 28 weeks (24 weeks treatment + 4 weeks follow up)	28 weeks
Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)	Number of patients with clinically significant changes in ECG will be reported. Monitored ECG parameters included heart rate (beats/min), PR interval (ms), PR interval Aggregate (ms), QRS duration aggregate (ms), QT interval aggregate (ms), QTcF interval aggregate (ms), and RR interval (ms), as well as the overall interpretation of each subject's ECG recorded as Normal, Abnormal Not Clinically Significant, or Abnormal Clinically Significant.	28 weeks
Safety - Changes in Blood Pressure From Baseline	Changes in blood pressure are reported at Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 The data collected data are of seated diastolic and systolic blood pressure (mmHg). During treatment phase visits, vital signs were collected before investigational product injection.	Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Safety - Changes in Body Temperature From Baseline	Changes in body temperature are reported The body temperature (ºC or ºF) was measured according to the site's usual procedure. During treatment phase visits, vital signs were collected before investigational product injection.	28 weeks
Immunogenicity - Occurrence of Anti-drug Antibodies	Occurrence of antibodies against glepaglutide The occurrence of glepaglutide-binding antibodies (ADA), M2 binding antibodies (M2 BAb), glepaglutide neutralizing antibodies (NAb) and GLP-2 cross-reacting antibodies (GLP-2 CR) was tested.	28 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2018
• Primary Completion (Actual): July 26, 2022
• Study Completion (Actual): July 26, 2022

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Intestinal Diseases; Disease; Digestive System Diseases; Gastrointestinal Diseases; Malabsorption Syndromes; Syndrome; Short Bowel Syndrome
• Other Study ID Numbers: ZP1848-17111

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: Yes
• Studies a U.S. FDA-regulated device product: No