Clinical trial NCT02690025: A Phase 2 Trial Testing ZP1848 in Patients With SBS
Official title: A Phase 2 Trial Testing ZP1848 in Patients With SBS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Short Bowel Syndrome
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
Collaborators: name: Larix A/S
First posted: 2016-02-24
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 3 weeks
Secondary outcomes:
measure: 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
timeFrame: 3 weeks
measure: Absolute change from baseline to the end of treatment of urine weight measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Relative change from baseline to the end of treatment of urine weight measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Absolute change from baseline to the end of treatment of wet weight absorption measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Relative change from baseline to the end of treatment of wet weight absorption measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Absolute change from baseline to the end of treatment of the intestinal absorption of electrolytes measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Relative change from baseline to the end of treatment of the intestinal absorption of electrolytes measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Absolute change from baseline to the end of treatment of the intestinal absorption of macronutrients measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Relative change from baseline to the end of treatment of the intestinal absorption of macronutrients measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Change in SF-36 score
timeFrame: 3 weeks
measure: Incidence of Adverse Events
timeFrame: 15 weeks
measure: Incidence of Anti Drug Antibodies
timeFrame: 15 weeks
measure: Absolute change from baseline to the end of treatment of urine weight minus oral intake measured separately over each of the two treatment periods
timeFrame: 3 weeks
measure: Relative change from baseline to the end of treatment of urine weight minus oral intake measured separately over each of the two treatment periods
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Zealand Pharma A/S
name: Gertrud Koefoed Rasmussen, MSc
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.