Extension trial to evaluate long-termefficacy and safety of glepaglutide in patients with short bowel syndrome

Phase 1

Conditions: Short bowel syndrome
MedDRA version: 20.1Level: PTClassification code 10049416Term: Short-bowel syndromeSystem Organ Class: 10017947 - Gastrointestinal disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2018-001429-26-DK

Lead Sponsor: Zealand Pharma A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 145

Inclusion Criteria

Patients rolling over from the lead-in trial:
The patient must meet all of the following inclusion criteria:
1. Signed informed consent
2. Either of the following:
a) Completed the full Treatment phase of the lead-in trial (ZP1848-17111), regardless of treatment adherence.
OR
b) Eligible based on the same inclusion/exclusion criteria as in the lead-in
trial (patients may be
directly screened into this trial)
Patients screened directly to the Extension Trial
The patient must meet all of the following inclusion criteria:
1. Informed consent obtained before any trial-related activity.
2. Age = 18 years and = 90 years at Screening.
3. Diagnosis of SBS defined as remaining small bowel in continuity of
estimated less than 200 cm [equal to 79 inches] and with the latest
intestinal resection being at least 6 months prior to Screening and
considered stable with regard to PS need. No restorative surgery
planned in the trial period.
4. Requiring PS at least 3 days per week.
5. Willing to adhere to an individual pre-defined drinking menu during
48-hours measuring intervals.
6. Willing to maintain a stable weight (± 5%) for the duration of the
trial (24 weeks).
7. Having:
a. A stoma Or
b. Colon-in-Continuity (CiC) with documented colonoscopy performed
during Screening and which does not give rise to any safety concerns.
Note: A colonoscopy performed within 6 months prior to Screening and
not giving rise to any safety concerns is acceptable. 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) (if standard of care at site) will suffice at the
discretion of the Investigator.
8. Having:
a) a stoma Or
b) colon-in-continuity (CiC) and able to separate stool and urine during
the 48 hours measuring intervals.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 99
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

Exclusion Criteria

Patients rolling over from the lead-in trial:
The patient must be excluded from this trial if any of the following criteria are met:
1. Withdrew consent from lead-in trial.
2. 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 confounds planned assessments of the trial.
3. Use of GLP-1, GLP-2, human growth hormone (HGH), dipeptidyl
peptidase-4 (DPP-4) inhibitors, citrulline, somatostatin, or analogs
thereof within 3 months. Note: Prior glepaglutide trial drug is allowed.
4. Females of childbearing potential, who are pregnant, breast-feeding,
intend to become pregnant, or are not using highly effective
contraceptive methods. Highly effective contraception methods and
definition of child-bearing potential are described in Section 11.4.4.
5. Committed to an institution by virtue of an order issued either by the
judicial or the administrative authorities.
6. An employee of the sponsor or Investigator or otherwise dependent
on them.
Patients screened directly to the Extension Trial
The patient must be excluded from the trial if he or she meets any of the
following criteria:
1. More than 2 SBS-related or PS-related hospitalizations (e.g., catheter
related bacteremia/sepsis, bowel obstruction, severe water-electrolytes
disturbances, etc.) within 6 months prior to Screening.
2. Poorly controlled inflammatory bowel disease (IBD) that is
moderately or severely active or fistula interfering with measurements
or examinations required in the trial.
3. Bowel obstruction.
4. Known radiation enteritis or significant villous atrophy, e.g., due to
active celiac disease.
5.Cardiac disease defined as: decompensated heart failure (New York
Heart Association [NYHA] Class III-IV), unstable angina pectoris, and.
6. Clinically significant abnormal ECG as judged by the Investigator.
7. Repeated (2 or more consecutive measurements separated by at
least 15 minutes) systolic blood pressure measurements > 180 mm Hg.
8. Human immunodeficiency virus (HIV) positive, acute liver disease, or
unstable chronic liver disease.
9. Any history of colon cancer. History of any other cancers (except
margin-free resected cutaneous basal or squamous cell carcinoma or
adequately treated in situ cervical cancer) unless disease-free state for
at least 5 years.
10. Estimated creatinine clearance (CrCL; by the Cockcroft-Gault
formula) < 30 mL/min.
11. Hepatic impairment defined as:
a. Total bilirubin = 2 × the upper limit of normal (ULN), or
b. Aspartate aminotransferase (AST) = 5 × ULN, or
c. Alanine aminotransferase (ALT) = 5× ULN
12. Use of GLP-1, GLP-2, HGH, somatostatin, or analogs thereof, within
3 months prior to Screening.
13. Use of DPP-4 inhibitors within 3 months prior to Screening.
14. Systemic immunosuppressive therapy that has been introduced or
has been unstable within 3 months prior to Screening.
15. Unstable biological therapy (e.g. anti-tumor necrosis factor alpha
[TNF-a], natalizumab, etc.) within 6 months prior to Screening, including
significant changes in doses or switch of drug.
16. Females of childbearing potential, who are pregnant, breastfeeding,
intend to become pregnant or are not using highly effective
contraceptive methods. Highly effective contraception methods and
definition of child-bearing potential are described in Section 11.4.4.
17. Known or suspected hypersensitivity to glepaglutide or related
products.
18. Previous exposure to glepaglutide.
19. Pre