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

Short Bowel Syndrome Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03690206
• Other study ID #: ZP1848-17111
• Status: Completed
• Phase: Phase 3
• Start date: October 4, 2018
• Est. completion date: July 26, 2022

Study information

• Verified date: May 2023
• Source: Zealand Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: July 26, 2022
• Est. primary completion date: July 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• glepaglutide
Glucagon-Like Peptide-2 (GLP-2) analog
• Placebo
Placebo for glepaglutide

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Zealand Pharma

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  France,  Germany,  Netherlands,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in weekly Parenteral Support (PS) volume	Change in weekly PS volume from baseline	24 weeks
Secondary	Clinical response in PS volume	Achieving at least 20 percent reduction in weekly PS volume from baseline	20 and 24 weeks
Secondary	Days off PS	Achieving 1 or more days per week off PS	24 weeks
Secondary	Clinical response in PS volume	Reduction of at least 20 percent in PS volume from baseline	12 and 24 weeks
Secondary	Weaned off PS	Reduction in weekly PS volume of 100 percent (weaned off)	24 weeks
Secondary	Fluid composite effect	Change in fluid composite effect from baseline	24 weeks
Secondary	Energy content	Change in energy content of PS from baseline	24 weeks
Secondary	Days on PS	Change in number of days on PS per week from baseline	24 weeks
Secondary	Change in PS volume per week	Achieving 40 percent in PS volume from baseline	20 and 24 weeks
Secondary	Patient Global Impression of Change scale (PGIC)	Change PGIC	24 weeks
Secondary	Safety - Adverse Events	Incidence and type of Adverse Events	28 weeks
Secondary	Number of patients with clinically significant changes in 12-Lead electrocardiogram (ECG)	Number of patients with clinically significant changes in ECG will be reported	28 weeks
Secondary	Safety - Changes in blood pressure from baseline	Changes in blood pressure will be reported	28 weeks
Secondary	Safety - Changes in body temperature from baseline	Changes in body temperature will be reported	28 weeks
Secondary	Immunogenicity - Occurrence of anti-drug antibodies	Occurrence of antibodies against glepaglutide	28 weeks