A Phase 2 Trial Testing ZP1848 in Patients With SBS (glepaglutide)

A proof-of-concept, dose finding, controlled, single-center, randomized, double-blind, fixed dose phase 2 trial with ZP1848 in patients with Short Bowel Syndrome.

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: ZP1848

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Following receipt of verbal and written information about the trial, the patient must provide signed informed consent before any trial related activity is carried out.
• Age ≥ 18 years and ≤ 90 years
• Stable SBS patients with intestinal insufficiency or failure, where the last surgical resection of gut tissue was performed at least 1 year ago
• A stable PS volume ( < 25% change in volume or energy content) for four weeks prior to randomization for patients requiring PS
• Wet weight of fecal excretion ≥ 1500 g/day demonstrated during a hospital stay prior to screening or during at least one day of the first baseline balance study.
• Stable body weight (<5% weight deviance in the three months prior to screening)

Exclusion Criteria:

• Patients with known or suspected intestinal strictures of clinical relevance as judged by the Investigator
• Active inflammatory bowel disease (IBD) or fistula during the screening period as judged by conventional means of the Investigator.
• Crohn's disease patients not being in clinical remission for the last 12 weeks prior to randomization
• Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months prior to screening
• History of cancer (except resected cutaneous basal or squamous cell carcinoma and except in situ cervical cancer) unless it can be documented that the patient has been in a disease-free state for at least 5 years (except colon cancer: patients with a history of colon cancer generally have to be excluded)
• eGFR (by the MDRD formula) <30 mL/min/1.73 m2
• Clinically meaningful renal disease as judged by the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZP1848 High dose; s.c. administration of high dose	Drug: ZP1848
Experimental: ZP1848 Medium dose; s.c. administration of medium dose	Drug: ZP1848
Experimental: ZP1848 Low dose; s.c. administration of low dose	Drug: ZP1848

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Primary endpoint is the absolute change from baseline to the end of three week treatment periods of wet weight of ostomy output or diarrhea measured separately over each of the two treatment periods.	3 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Relative change from baseline to the end of treatment of wet weight of ostomy output or diarrhea measured separately over each of the two treatment periods	3 weeks
Absolute change from baseline to the end of treatment of urine weight measured separately over each of the two treatment periods	3 weeks
Relative change from baseline to the end of treatment of urine weight measured separately over each of the two treatment periods	3 weeks
Absolute change from baseline to the end of treatment of wet weight absorption measured separately over each of the two treatment periods	3 weeks
Relative change from baseline to the end of treatment of wet weight absorption measured separately over each of the two treatment periods	3 weeks
Absolute change from baseline to the end of treatment of the intestinal absorption of electrolytes measured separately over each of the two treatment periods	3 weeks
Relative change from baseline to the end of treatment of the intestinal absorption of electrolytes measured separately over each of the two treatment periods	3 weeks
Absolute change from baseline to the end of treatment of the intestinal absorption of macronutrients measured separately over each of the two treatment periods	3 weeks
Relative change from baseline to the end of treatment of the intestinal absorption of macronutrients measured separately over each of the two treatment periods	3 weeks
Change in SF-36 score	3 weeks
Incidence of Adverse Events	15 weeks
Incidence of Anti Drug Antibodies	15 weeks
Absolute change from baseline to the end of treatment of urine weight minus oral intake measured separately over each of the two treatment periods	3 weeks
Relative change from baseline to the end of treatment of urine weight minus oral intake measured separately over each of the two treatment periods	3 weeks

Collaborators and Investigators

• Sponsor: Zealand Pharma
• Collaborators: Larix A/S
• Investigators: Study Director: Gertrud Koefoed Rasmussen, MSc, Zealand Pharma A/S

Publications and helpful links

General Publications

• Hvistendahl MK, Naimi RM, Hansen SH, Rehfeld JF, Kissow H, Pedersen J, Dragsted LO, Sonne DP, Knop FK, Jeppesen PB. Bile acid-farnesoid X receptor-fibroblast growth factor 19 axis in patients with short bowel syndrome: The randomized, glepaglutide phase 2 trial. JPEN J Parenter Enteral Nutr. 2022 May;46(4):923-935. doi: 10.1002/jpen.2224. Epub 2021 Sep 1.
• Naimi RM, Hvistendahl M, Nerup N, Ambrus R, Achiam MP, Svendsen LB, Gronbaek H, Moller HJ, Vilstrup H, Steensberg A, Jeppesen PB. Effects of glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, on markers of liver status in patients with short bowel syndrome: findings from a randomised phase 2 trial. EBioMedicine. 2019 Aug;46:444-451. doi: 10.1016/j.ebiom.2019.07.016. Epub 2019 Jul 17.
• Naimi RM, Hvistendahl M, Enevoldsen LH, Madsen JL, Fuglsang S, Poulsen SS, Kissow H, Pedersen J, Nerup N, Ambrus R, Achiam MP, Svendsen LB, Holst JJ, Hartmann B, Hansen SH, Dragsted LO, Steensberg A, Mouritzen U, Hansen MB, Jeppesen PB. Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2019 May;4(5):354-363. doi: 10.1016/S2468-1253(19)30077-9. Epub 2019 Mar 15.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: February 12, 2016
• First Submitted That Met QC Criteria: February 18, 2016
• First Posted (Estimate): February 24, 2016

Study Record Updates

• Last Update Posted (Actual): June 21, 2017
• Last Update Submitted That Met QC Criteria: June 20, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Short Bowel Syndrome
• Other Study ID Numbers: ZP1848-15073

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO