NCT03690206: EASE SBS 1

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

Completed Phase 3 Results posted Last updated 17 July 2025

What this trial tests

Phase 3 trial testing glepaglutide in Short Bowel Syndrome in 106 participants. Completed in 26 July 2022.

Timeline

4 October 2018

Primary endpoint
26 July 2022

26 July 2022

Quick facts

Lead sponsor	Zealand Pharma
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	106
Start date	4 October 2018
Primary completion	26 July 2022
Estimated completion	26 July 2022
Sites	29 locations across Denmark, France, Netherlands, Belgium, United Kingdom, Germany, Poland, Canada

Drugs / interventions tested

• glepaglutide — full drug profile →
• Placebo

Conditions studied

• Short Bowel Syndrome — all drugs for Short Bowel Syndrome →

Sponsor

Zealand Pharma — full company profile →

Who can join

Adults 18 to 90, any sex, with Short Bowel Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Weekly Parenteral Support (PS) Volume Primary · 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.

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	-5.13	-6.24 – -4.02
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	-3.76	-4.96 – -2.56
Placebo SC Injections Twice Weekly	-2.85	-3.93 – -1.77

Clinical Response in PS Volume Secondary · 20 and 24 weeks

Clinical response, defined as at least 20% reduction in actual weekly PS volume from baseline to both Weeks 20 and 24.

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	23
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	16
Placebo SC Injections Twice Weekly	14

Days Off PS Secondary · 24 weeks

Achieving 1 or more days per week off PS

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	18
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	12
Placebo SC Injections Twice Weekly	7

Clinical Response in PS Volume Secondary · 12 and 24 weeks

Reduction of at least 20 percent in PS volume from baseline to both 12 and 24 weeks.

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	19
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	15
Placebo SC Injections Twice Weekly	13

Weaned Off PS Secondary · 24 weeks

Reduction in weekly PS volume of 100 percent (weaned off)

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	5
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	4
Placebo SC Injections Twice Weekly	0

Energy Content Secondary · 24 weeks

Change in weekly energy content of PS from baseline

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	-7360.6	-48521 – 130351
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	-3085.9	-56550 – 1423
Placebo SC Injections Twice Weekly	-734.2	-46307 – 1670

Days on PS Secondary · 24 weeks

Change in number of days on PS per week from baseline

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	-1.00	-5.0 – 0.0
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	0.00	-7.0 – 1.0
Placebo SC Injections Twice Weekly	0.00	-4.0 – 0.0

Change in PS Volume Per Week Secondary · 20 and 24 weeks

Achieving reduction of at least 40 percent in PS volume from baseline to both 20 and 24 weeks

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	15
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	10
Placebo SC Injections Twice Weekly	8

Patient Global Impression of Change Scale (PGIC) Secondary · 24 weeks

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 "Minima

PGIC improved

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	22
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	27
Placebo SC Injections Twice Weekly	13

PGIC much/very much improved

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	17
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	11
Placebo SC Injections Twice Weekly	2

Safety - Adverse Events Secondary · 28 weeks

Incidence and type of Adverse Events over an average of 28 weeks (24 weeks treatment + 4 weeks follow up)

All AEs

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	33
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	33
Placebo SC Injections Twice Weekly	27

Serious adverse events

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	9
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	10
Placebo SC Injections Twice Weekly	7

AE Severity: Severe

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	10
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	5
Placebo SC Injections Twice Weekly	2

AE Severity: Moderate

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	15
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	18
Placebo SC Injections Twice Weekly	14

AE Severity: Mild

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	28
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	32
Placebo SC Injections Twice Weekly	24

Relationship: Related

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	27
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	26
Placebo SC Injections Twice Weekly	14

Relationship: Unlikely related

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	18
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	16
Placebo SC Injections Twice Weekly	9

Relationship: Not related

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	26
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	26
Placebo SC Injections Twice Weekly	23

Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Secondary · 28 weeks

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.

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	0
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	0
Placebo SC Injections Twice Weekly	0

Safety - Changes in Blood Pressure From Baseline Secondary · Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24

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 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	-2.8	-7.6 – 2.0
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	0.3	-4.1 – 4.7
Placebo SC Injections Twice Weekly	-4.5	-8.2 – -0.7

Week 2 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	1.0	-3.2 – 5.1
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	-0.1	-4.6 – 4.4
Placebo SC Injections Twice Weekly	-2.7	-6.4 – 1.0

Week 4 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	-1.7	-6.5 – 3.1
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	-0.2	-3.9 – 3.4
Placebo SC Injections Twice Weekly	-0.3	-4.6 – 3.9

Week 8 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	0.3	-5.4 – 6.0
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	-1.5	-5.9 – 2.9
Placebo SC Injections Twice Weekly	-2.5	-6.9 – 1.8

Week 12 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	-4.4	-9.6 – 0.8
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	3.3	-1.0 – 7.6
Placebo SC Injections Twice Weekly	-0.4	-5.0 – 4.1

Week 16 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	0.1	-5.6 – 5.8
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	0.4	-4.7 – 5.5
Placebo SC Injections Twice Weekly	-1.1	-6.3 – 4.1

Week 20 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	1.3	-5.8 – 8.3
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	1.2	-3.6 – 6.0
Placebo SC Injections Twice Weekly	-1.0	-6.2 – 4.3

Week 24 Systolic blood pressure

Group	Value	95% CI
Glepaglutide SC Injections Twice Weekly	-1.0	-6.2 – 4.1
Glepaglutide SC Injections Once Weekly and Placebo Once Weekly	-1.1	-5.6 – 3.4
Placebo SC Injections Twice Weekly	-5.9	-11.0 – -0.8

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs, whether serious or non-serious, were to be reported from the time a signed and dated Informed Consent Form (ICF) was obtained until the end of the post-treatment follow-up period on average 28 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Glepaglutide SC Injections Twice Weekly

Serious: 9/35 (26%)

Deaths: 0/35

Glepaglutide SC Injections Once Weekly and Placebo Once Weekly

Serious: 10/35 (29%)

Deaths: 0/35

Placebo SC Injections Twice Weekly

Serious: 7/36 (19%)

Deaths: 0/36

Serious adverse events (24 terms)

Reaction	System	Glepaglutide SC Injections…	Glepaglutide SC Injections…	Placebo SC Injections Twic…
Pyrexia	General disorders	—	—	—
Device related sepsis	Infections and infestations	—	—	—
Vascular device infection	Infections and infestations	—	—	—
Stoma site haemorrhage	Injury, poisoning and procedural complications	—	—	—
Acetabulum fracture	Injury, poisoning and procedural complications	—	—	—
Alcohol poisoning	Injury, poisoning and procedural complications	—	—	—
Procedural pneumothorax	Injury, poisoning and procedural complications	—	—	—
Peripheral arterial occlusive disease	Vascular disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Blood loss anaemia	Blood and lymphatic system disorders	—	—	—
Iron deficiency anaemia	Blood and lymphatic system disorders	—	—	—
Catheter site necrosis	General disorders	—	—	—
Hypersensitivity	Immune system disorders	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—
Infection	Infections and infestations	—	—	—
Large intestine infection	Infections and infestations	—	—	—
COVID-19	Infections and infestations	—	—	—
Gastrointestinal viral infection	Infections and infestations	—	—	—
Device breakage	Product Issues	—	—	—
Device malfunction	Product Issues	—	—	—
Metabolic acidosis	Metabolism and nutrition disorders	—	—	—

Other adverse events (49 terms — click to expand)

Reaction	System	Glepaglutide SC Injections…	Glepaglutide SC Injections…	Placebo SC Injections Twic…
Injection site reaction	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Injection site erythema	General disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Stoma site oedema	Injury, poisoning and procedural complications	—	—	—
Headache	Nervous system disorders	—	—	—
Pyrexia	General disorders	—	—	—
Fatigue	General disorders	—	—	—
Injection site pain	General disorders	—	—	—
Injection site induration	General disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Injection site pruritus	General disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Injection site irritation	General disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Gastrointestinal bacterial overgrowth	Infections and infestations	—	—	—
Weight decreased	Investigations	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Stoma complication	Injury, poisoning and procedural complications	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—
Feeling hot	General disorders	—	—	—
Injection site rash	General disorders	—	—	—
Malaise	General disorders	—	—	—
Complication associated with device	General disorders	—	—	—
Injection site swelling	General disorders	—	—	—
Iron deficiency anaemia	Blood and lymphatic system disorders	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—
Abdominal pain lower	Gastrointestinal disorders	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—

Most-reported serious reactions: Pyrexia, Device related sepsis, Vascular device infection, Stoma site haemorrhage, Acetabulum fracture, Alcohol poisoning, Procedural pneumothorax, Peripheral arterial occlusive disease.

Data from ClinicalTrials.gov NCT03690206 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. A nanoparticle platform for combined mucosal healing and immunomodulation in inflammatory bowel disease treatment.
   Marotti V, Xu Y, Bohns Michalowski C, Zhang W, et al · · 2024 · cited 26× · PMID 37859689 · DOI 10.1016/j.bioactmat.2023.09.014
2. Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial.
   Jeppesen PB, Vanuytsel T, Subramanian S, Joly F, et al · · 2025 · cited 16× · PMID 39708985 · DOI 10.1053/j.gastro.2024.11.023
3. Glepaglutide-Loaded Foam for the Induction of Mucosal Healing in the Treatment of Inflammatory Bowel Disease.
   Zhang W, Van den Bossche W, Yagoubi H, Kambale EK, et al · · 2025 · cited 2× · PMID 39905897 · DOI 10.1002/adhm.202403497
4. Glucagon-Like Peptide-2 (GLP-2) Analogues in Patients With Short Bowel Syndrome Dependent on Parenteral Support: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
   Hyder A, Alria A, Rafiq A, Akram MF, et al · · 2025 · cited 1× · PMID 41424579 · DOI 10.1002/jgh3.70327