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

Zealand Pharma106 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

106

Conditions

Short Bowel Syndrome

Interventions

glepaglutideDRUG

Glucagon-Like Peptide-2 (GLP-2) analog

PlaceboDRUG

Placebo for glepaglutide

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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.

Locations (29)

Outcomes

Primary Outcomes

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.

Time frame: 24 weeks

Secondary Outcomes

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.

Time frame: 20 and 24 weeks

Days Off PS

Achieving 1 or more days per week off PS

Time frame: 24 weeks

Clinical Response in PS Volume

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

Time frame: 12 and 24 weeks

Weaned Off PS

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

Time frame: 24 weeks

Energy Content

Change in weekly energy content of PS from baseline

Time frame: 24 weeks

Days on PS

Change in number of days on PS per week from baseline

Time frame: 24 weeks

Data from ClinicalTrials.gov

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Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University of Chicago Children's Hospital

Chicago, Illinois, United States

Mayo Clinic College of Medicine

Rochester, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Mount Sinai Hospital

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Vanderbilt University Medical Center, Nashville

Nashville, Tennessee, United States

UZ Leuven

Leuven, Belgium

The Royal Alexandra Hospital

Edmonton, Canada

Western University

London, Canada

...and 19 more locations

Change in PS Volume Per Week

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

Time frame: 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.

Time frame: 24 weeks

Safety - Adverse Events

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

Time frame: 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.

Time frame: 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.

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

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.

Time frame: 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.

Time frame: 28 weeks