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

Study Overview
=================
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).

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)

Conditions
-----------------
Short Bowel Syndrome

Intervention / Treatment
-----------------
* Drug: glepaglutide
* Drug: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glepaglutide SC injections twice weekly<br>Intervention: Glepaglutide | Drug: glepaglutide<br>* Glucagon-Like Peptide-2 (GLP-2) analog<br>* Other names: ZP1848;|
| Experimental: Glepaglutide SC injections once weekly and placebo once weekly<br>Intervention: Glepaglutide | Drug: glepaglutide<br>* Glucagon-Like Peptide-2 (GLP-2) analog<br>* Other names: ZP1848;Drug: Placebo<br>* Placebo for glepaglutide<br>|
| Placebo Comparator: Placebo SC injections twice weekly<br>Intervention: Placebo | Drug: Placebo<br>* Placebo for glepaglutide<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weekly Parenteral Support (PS) volume | Change in weekly PS volume from baseline | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response in PS volume | Achieving at least 20 percent reduction in weekly PS volume from baseline | 20 and 24 weeks | 
| Days off PS | Achieving 1 or more days per week off PS | 24 weeks | 
| Clinical response in PS volume | Reduction of at least 20 percent in PS volume from baseline | 12 and 24 weeks | 
| Weaned off PS | Reduction in weekly PS volume of 100 percent (weaned off) | 24 weeks | 
| Fluid composite effect | Change in fluid composite effect from baseline | 24 weeks | 
| Energy content | Change in energy content of PS from baseline | 24 weeks | 
| Days on PS | Change in number of days on PS per week from baseline | 24 weeks | 
| Change in PS volume per week | Achieving 40 percent in PS volume from baseline | 20 and 24 weeks | 
| Patient Global Impression of Change scale (PGIC) | Change PGIC | 24 weeks | 
| Safety - Adverse Events | Incidence and type of Adverse Events | 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 | 28 weeks | 
| Safety - Changes in blood pressure from baseline | Changes in blood pressure will be reported | 28 weeks | 
| Safety - Changes in body temperature from baseline | Changes in body temperature will be reported | 28 weeks | 
| Immunogenicity - Occurrence of anti-drug antibodies | Occurrence of antibodies against glepaglutide | 28 weeks |