Evaluation of Long Term Safety and Efficacy of Glepaglutide in Treatment of SBS - Extension Trial

Study Overview
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Brief Summary
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This trial is an extension trial to EASE SBS 2. The study looks at whether glepaglutide is a safe treatment for participants with Short Bowel Syndrome (SBS), as well as how well effectiveness is maintained during long term treatment. Participants in this trial will receive glepaglutide as once-weekly injections under the skin (subcutaneous, s.c.) for approximately 2 years.

Official Title
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A 104-Week, Multicenter, Single-Arm, Long-Term, Phase 3 Extension Trial Investigating the Safety and Efficacy of Glepaglutide in Adult Patients With Short Bowel Syndrome (SBS) Completing the EASE SBS 2 Trial

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Glepaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activity Completed the full treatment period of the extension trial EASE SBS 2 (ZP1848-17127) Exclusion Criteria: Any condition, disease, or circumstance that in the Investigator's opinion would put the patient at any undue risk, prevent completion of the trial, or confound the planned assessments of the trial Not having a colonoscopy performed at End of Trial in EASE SBS 2 (for patients with remnant colon). Note. The results of the colonoscopy must not give rise to any safety concerns. A colonoscopy performed within 6 months prior to End of Trial and not giving rise to any safety concerns is accepted. For patients with a remnant colon, which is not connected to the passage of foods and is thereby dormant, a computerized tomography (CT) scan or magnetic resonance imaging (MRI) will suffice at the discretion of the Investigator Use of GLP-1, GLP-2, human growth hormone (HGH), dipeptidyl peptidase-4 (DPP-4) inhibitors, somatostatin, or analogs thereof within 3 months. Note: Prior use of glepaglutide trial drug is allowed Females of childbearing potential, who are pregnant, breast-feeding, intend to become pregnant, or are not using highly effective contraceptive methods

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: once-weekly glepaglutide<br>All participants will receive 10 mg of glepaglutide as once-weekly injections under the skin (subcutaneous, s.c.) | Drug: Glepaglutide<br>* Glepaglutide will be delivered in a single-use autoinjector.<br>* Other names: ZP1848;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and type of Adverse Events (AEs) | For AEs with onset or worsening following Visit 1 | After 108 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and type of Serious Adverse Events (SAEs) | For AEs with onset or worsening following Visit 1 | After 108 weeks | 
| Incidence and type of Adverse Events of Special Interest (AESIs) | For AEs with onset or worsening following Visit 1 | After 108 weeks | 
| Change in body temperature |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in heart rate |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in blood pressure | Seated diastolic and systolic blood pressure | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in body weight |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Number of participants with clinically significant changes in 12-Lead electrocardiogram (ECG) |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in hematology - hemoglobin |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in hematology - hematocrit |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in hematology - white blood cell count |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in hematology - platelet count |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - sodium |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - potassium |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - chloride |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - bicarbonate |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - blood urea nitrogen |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - creatinine |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - creatinine clearance |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - glucose |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - calcium |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - phosphorous |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - alkaline phosphatase |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - alanine aminotransferase (ALT) |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - aspartate aminotransferase (AST) |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - International Normalized Ratio (INR) |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - gamma-glutamyl transferase (GGT) |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - lactic dehydrogenase |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - conjugated bilirubin |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - total bilirubin |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - total protein |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - albumin |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - amylase |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - uric acid |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in biochemistry - C-reactive protein |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - blood |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - glucose |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - leukocytes |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - pH |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - osmolality |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - protein |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - sodium |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Change in urinalysis - potassium |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Anti-glepaglutide antibodies |  | Week 0, Week 108 | 
| Antibody reactivity to ZP1848 |  | Week 0, Week 108 | 
| Cross-reactivity to glucagon-like peptide-2 (GLP-2) |  | Week 0, Week 108 | 
| Glepaglutide neutralizing antibodies |  | Week 0, Week 108 | 
| Reduction in weekly Parenteral Support (PS) volume |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Reduction of at least 20 percent in weekly PS volume |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Reduction in days on PS greater than or equal to 1 day per week |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 | 
| Reduction in weekly PS volume of 100 percent (weaned off) |  | Week 0 in lead-in trial (EASE SBS 1), Week 108 |