Efficacy And Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS)
- Registration Number
- NCT03690206
- Lead Sponsor
- Zealand Pharma
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 106
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Glepaglutide SC injections once weekly and placebo once weekly glepaglutide Intervention: Glepaglutide Glepaglutide SC injections once weekly and placebo once weekly Placebo Intervention: Glepaglutide Placebo SC injections twice weekly Placebo Intervention: Placebo Glepaglutide SC injections twice weekly glepaglutide Intervention: Glepaglutide
- Primary Outcome Measures
Name Time Method Change in Weekly Parenteral Support (PS) Volume 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.
- Secondary Outcome Measures
Name Time Method Clinical Response in PS Volume 12 and 24 weeks Reduction of at least 20 percent in PS volume from baseline to both 12 and 24 weeks.
Days Off PS 24 weeks Achieving 1 or more days per week off PS
Weaned Off PS 24 weeks Reduction in weekly PS volume of 100 percent (weaned off)
Energy Content 24 weeks Change in weekly energy content of PS from baseline
Days on PS 24 weeks Change in number of days on PS per week from baseline
Change in PS Volume Per Week 20 and 24 weeks Achieving reduction of at least 40 percent in PS volume from baseline to both 20 and 24 weeks
Patient Global Impression of Change Scale (PGIC) 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 "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.
Safety - Adverse Events 28 weeks Incidence and type of Adverse Events over an average of 28 weeks (24 weeks treatment + 4 weeks follow up)
Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) 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.
Safety - Changes in Blood Pressure From Baseline 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.
Safety - Changes in Body Temperature From Baseline 28 weeks 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.
Immunogenicity - Occurrence of Anti-drug Antibodies 28 weeks 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.
Trial Locations
- Locations (29)
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Bénite, France
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of Chicago Children's Hospital
🇺🇸Chicago, Illinois, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Asklepios Kliniken Hamburg GmbH
🇩🇪Hamburg, Germany
St Mark's Hospital
🇬🇧Harrow, United Kingdom
Aalborg University Hospital
🇩🇰Aalborg, Denmark
The Royal Alexandra Hospital
🇨🇦Edmonton, Canada
Vanderbilt University Medical Center, Nashville
🇺🇸Nashville, Tennessee, United States
University Health Network - Toronto General Hospital
🇨🇦Toronto, Canada
UMC Radboud Nijmegen
🇳🇱Nijmegen, Netherlands
Solumed
🇵🇱Poznań, Poland
Szpital Skawina sp. z o.o. im. Stanley Dudricka
🇵🇱Skawina, Poland
Mayo Clinic College of Medicine
🇺🇸Rochester, Minnesota, United States
Western University
🇨🇦London, Canada
UZ Leuven
🇧🇪Leuven, Belgium
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Rigshospitalet
🇩🇰Copenhagen, Denmark
Hôpital Beaujon
🇫🇷Clichy, France
Universitätsklinikum Frankfurt - Med. Klinik I
🇩🇪Frankfurt, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Universitätsmedizin Rostock
🇩🇪Rostock, Germany
Wojewodzki Specjalistyczny Szpital im. M. Pirogowa w Lodzi
🇵🇱Łódź, Poland
UCLH Foundation NHS Trust
🇬🇧London, United Kingdom
Salford Royal NHS Foundation Trust
🇬🇧Manchester, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom
University of East Anglia
🇬🇧Norwich, United Kingdom