Clinical trial NCT03690206: Efficacy And Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
First posted: 2018-10-01
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Weekly Parenteral Support (PS) Volume
timeFrame: 24 weeks
Secondary outcomes:
measure: Clinical Response in PS Volume
timeFrame: 20 and 24 weeks
measure: Days Off PS
timeFrame: 24 weeks
measure: Clinical Response in PS Volume
timeFrame: 12 and 24 weeks
measure: Weaned Off PS
timeFrame: 24 weeks
measure: Energy Content
timeFrame: 24 weeks
measure: Days on PS
timeFrame: 24 weeks
measure: Change in PS Volume Per Week
timeFrame: 20 and 24 weeks
measure: Patient Global Impression of Change Scale (PGIC)
timeFrame: 24 weeks
measure: Safety - Adverse Events
timeFrame: 28 weeks
measure: Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)
timeFrame: 28 weeks
measure: Safety - Changes in Blood Pressure From Baseline
timeFrame: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
measure: Safety - Changes in Body Temperature From Baseline
timeFrame: 28 weeks
measure: Immunogenicity - Occurrence of Anti-drug Antibodies
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Children's Hospital
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic College of Medicine
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Nashville
state: Tennessee
city: Leuven
country: Belgium
facility: UZ Leuven
city: Edmonton
country: Canada
facility: The Royal Alexandra Hospital
city: London
country: Canada
facility: Western University
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Clichy
country: France
facility: Hôpital Beaujon
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt - Med. Klinik I
city: Hamburg
country: Germany
facility: Asklepios Kliniken Hamburg GmbH
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Nijmegen
country: Netherlands
facility: UMC Radboud Nijmegen
city: Poznań
country: Poland
facility: Solumed
city: Skawina
country: Poland
facility: Szpital Skawina sp. z o.o. im. Stanley Dudricka
city: Łódź
country: Poland
facility: Wojewodzki Specjalistyczny Szpital im. M. Pirogowa w Lodzi
city: Harrow
country: United Kingdom
facility: St Mark's Hospital
city: London
country: United Kingdom
facility: UCLH Foundation NHS Trust
city: Manchester
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: University of East Anglia
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: Zealand Pharma
name: Study Director
role: STUDY_DIRECTOR
References: