Short Bowel SyndromePhase 3EASE SBS 1NCT03690206
Efficacy And Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS)
A Phase 3 study testing glepaglutide in people with Short Bowel Syndrome, run by Zealand Pharma at 29 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Short Bowel Syndrome
- What is being tested?
- glepaglutide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 29 sitesin 9 countries
- Study dates
- 4 Oct 2018to 26 Jul 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
29 sites in 9 countries.
29 sites in 9 countries
United States7 sites
University of Chicago Children's Hospital
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
Vanderbilt University Medical Center, Nashville
Nashville, Tennessee, 68198-3285
Mount Sinai Hospital
New York, New York, 10029
University of Nebraska Medical Center
Omaha, Nebraska, 68198-3285
Mayo Clinic College of Medicine
Rochester, Minnesota, 55905
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Germany5 sites
Charité - Universitätsmedizin Berlin
Berlin
Universitätsklinikum Bonn
Bonn
Universitätsklinikum Frankfurt - Med. Klinik I
Frankfurt
Asklepios Kliniken Hamburg GmbH
Hamburg
Universitätsmedizin Rostock
Rostock
United Kingdom5 sites
St Mark's Hospital
Harrow
UCLH Foundation NHS Trust
London
Salford Royal NHS Foundation Trust
Manchester
University of East Anglia
Norwich
University Hospital Southampton NHS Foundation Trust
Southampton
Canada3 sites
The Royal Alexandra Hospital
Edmonton
Western University
London, N6A 4V2
University Health Network - Toronto General Hospital
Toronto
Poland3 sites
Wojewodzki Specjalistyczny Szpital im. M. Pirogowa w Lodzi
Lodz
Solumed
Poznan
Szpital Skawina sp. z o.o. im. Stanley Dudricka
Skawina
Denmark2 sites
Aalborg University Hospital
Aalborg, 9000
Rigshospitalet
Copenhagen
About this study
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)
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.
Read the 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).
- Conditions
- Short Bowel Syndrome
- Being tested
- glepaglutide, Placebo
- Medical subject headings
- Short Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glepaglutideDrug
Also called ZP1848
Glucagon-Like Peptide-2 (GLP-2) analog
PlaceboDrug
Placebo for glepaglutide
| Study group | Role | What they receive |
|---|---|---|
| Glepaglutide SC injections twice weekly | Experimental | Intervention: Glepaglutide Receives: Drug: glepaglutide |
| Glepaglutide SC injections once weekly and placebo once weekly | Experimental | Intervention: Glepaglutide Receives: Drug: glepaglutide; Drug: Placebo |
| Placebo SC injections twice weekly | Placebo comparator | Intervention: Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (13)
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.
Measured: 20 and 24 weeks
Days Off PS
Achieving 1 or more days per week off PS
Measured: 24 weeks
Clinical Response in PS Volume
Reduction of at least 20 percent in PS volume from baseline to both 12 and 24 weeks.
Measured: 12 and 24 weeks
Weaned Off PS
Reduction in weekly PS volume of 100 percent (weaned off)
Measured: 24 weeks
Energy Content
Change in weekly energy content of PS from baseline
Measured: 24 weeks
Days on PS
Change in number of days on PS per week from baseline
Measured: 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
Measured: 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.
Measured: 24 weeks
Safety - Adverse Events
Incidence and type of Adverse Events over an average of 28 weeks (24 weeks treatment + 4 weeks follow up)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2018
- Study start4 Oct 2018
- Primary completion26 Jul 2022
- Study completion26 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Short Bowel SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Zealand Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03690206
- Sponsor's protocol ID
- ZP1848-17111
- Acronym
- EASE SBS 1
- Status last verified
- Jun 2025
- First submitted
- 17 Sep 2018
- Last updated
- 17 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39708985
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03690206
- Acronym / sponsor ID
- EASE SBS 1 / ZP1848-17111
- Conditions
- Short Bowel Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Zealand PharmaIndustry (pharma, biotech, devices)
- Study start
- 4 Oct 2018 (actual)
- Primary completion
- 26 Jul 2022 (actual)
- Study completion
- 26 Jul 2022 (actual)
- First posted
- 1 Oct 2018 (actual)
- Results
- Posted 21 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Glepaglutide SC injections twice weekly | Experimental | Drug: glepaglutideIntervention: Glepaglutide |
| Glepaglutide SC injections once weekly and placebo once weekly | Experimental | Drug: glepaglutide, Drug: PlaceboIntervention: Glepaglutide |
| Placebo SC injections twice weekly | Placebo comparator | Drug: PlaceboIntervention: Placebo |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| glepaglutideAlso: ZP1848Glucagon-Like Peptide-2 (GLP-2) analog | Drug | Glepaglutide SC injections once weekly and placebo once weekly, Glepaglutide SC injections twice weekly |
| PlaceboPlacebo for glepaglutide | Drug | Glepaglutide SC injections once weekly and placebo once weekly, Placebo SC injections twice weekly |
Primary outcome
Change in Weekly Parenteral Support (PS) Volume
Time frame: 24 weeks
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.
13 secondary outcomes
Clinical Response in PS Volume
Time frame: 20 and 24 weeks
Days Off PS
Time frame: 24 weeks
Clinical Response in PS Volume
Time frame: 12 and 24 weeks
Weaned Off PS
Time frame: 24 weeks
Energy Content
Time frame: 24 weeks
Days on PS
Time frame: 24 weeks
Change in PS Volume Per Week
Time frame: 20 and 24 weeks
Patient Global Impression of Change Scale (PGIC)
Time frame: 24 weeks
Safety - Adverse Events
Time frame: 28 weeks
Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)
Time frame: 28 weeks
Safety - Changes in Blood Pressure From Baseline
Time frame: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Safety - Changes in Body Temperature From Baseline
Time frame: 28 weeks
Immunogenicity - Occurrence of Anti-drug Antibodies
Time frame: 28 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39708985Jeppesen 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Zealand Pharma
29 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing glepaglutide in people with Short Bowel Syndrome, run by Zealand Pharma at 29 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Germany, United Kingdom, Canada, Poland and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Weekly Parenteral Support (PS) Volume (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03690206, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2025.