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

NCT03690206 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ZP1848-17111
• Study Type: interventional
• Target: 106
• Locations: 9 countries
• Sites: 29

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.

Conditions

Short Bowel Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Clinical Response in PS Volume

  20 and 24 weeks

• Days Off PS

  24 weeks

• Clinical Response in PS Volume

  12 and 24 weeks

• Weaned Off PS

  24 weeks

• Energy Content

  24 weeks

Study Arms (3)

Glepaglutide SC injections twice weekly

EXPERIMENTAL

Intervention: Glepaglutide

Drug: glepaglutide

Glepaglutide SC injections once weekly and placebo once weekly

EXPERIMENTAL

Intervention: Glepaglutide

Drug: glepaglutide; Drug: Placebo

Placebo SC injections twice weekly

PLACEBO COMPARATOR

Intervention: Placebo

Drug: Placebo

Interventions

glepaglutide DRUG

Glucagon-Like Peptide-2 (GLP-2) analog

Also known as: ZP1848

Glepaglutide SC injections once weekly and placebo once weekly; Glepaglutide SC injections twice weekly

Placebo DRUG

Placebo for glepaglutide

Glepaglutide SC injections once weekly and placebo once weekly; Placebo SC injections twice weekly

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (29)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago Children's Hospital

Chicago, Illinois, 60637, United States

Location

Mayo Clinic College of Medicine

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-3285, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center, Nashville

Nashville, Tennessee, 68198-3285, United States

Location

UZ Leuven

Leuven, Belgium

Location

The Royal Alexandra Hospital

Edmonton, Canada

Location

Western University

London, N6A 4V2, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Canada

Location

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Rigshospitalet

Copenhagen, Denmark

Location

Hôpital Beaujon

Clichy, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, France

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Bonn

Bonn, Germany

Location

Universitätsklinikum Frankfurt - Med. Klinik I

Frankfurt, Germany

Location

Asklepios Kliniken Hamburg GmbH

Hamburg, Germany

Location

Universitätsmedizin Rostock

Rostock, Germany

Location

UMC Radboud Nijmegen

Nijmegen, Netherlands

Location

Wojewodzki Specjalistyczny Szpital im. M. Pirogowa w Lodzi

Lodz, Poland

Location

Solumed

Poznan, Poland

Location

Szpital Skawina sp. z o.o. im. Stanley Dudricka

Skawina, Poland

Location

St Mark's Hospital

Harrow, United Kingdom

Location

UCLH Foundation NHS Trust

London, United Kingdom

Location

Salford Royal NHS Foundation Trust

Manchester, United Kingdom

Location

University of East Anglia

Norwich, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

Related Publications (1)

• Jeppesen PB, Vanuytsel T, Subramanian S, Joly F, Wanten G, Lamprecht G, Kunecki M, Rahman F, Nielsen TSS, Berner-Hansen M, Pape UF, Mercer DF. Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial. Gastroenterology. 2025 Apr;168(4):701-713.e6. doi: 10.1053/j.gastro.2024.11.023. Epub 2024 Dec 19.

  PMID: 39708985 DERIVED

MeSH Terms

Conditions

Short Bowel Syndrome

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Head of clinical operations
• Organization: Zealand Pharma A/S

info@zealandpharma.com

+45 8877 3600

Study Officials

• Study Director

  Zealand Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: October 1, 2018
• Study Start: October 4, 2018
• Primary Completion: July 26, 2022
• Study Completion: July 26, 2022
• Last Updated: July 17, 2025
• Results First Posted: October 21, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); NL (1); CA (3); PL (3); DE (5); BE (1); FR (2); DK (2); GB (5)