EASE SBS 2 (Evaluation of the efficacy and safety of Glepaglutide in the treatment of short bowel syndrome) (SBS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zealand Pharma A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

30 Apr 2019 → 25 Mar 2026

Decision date (initial)

2024-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513374-22-00

EudraCT number

2018-001429-26

WHO UTN

U1111-1223-1464

ClinicalTrials.gov

NCT03905707

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the long-term safety of glepaglutide treatment in short bowel syndrome (SBS) patients

Secondary objectives 3

1. To evaluate the long-term efficacy of glepaglutide treatment in SBS patients
2. To evaluate the long-term immunogenicity of glepaglutide and its impact on pharmacokinetics (PK), efficacy, and safety in SBS patients
3. To evaluate quality of life for SBS patients treated with glepaglutide

Conditions and MedDRA coding

Short Bowel Syndrome

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Patients rolling over from the lead-in trial: Signed informed consent
2. Patients rolling over from the lead-in trial: 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)

Exclusion criteria 30

1. Patients rolling over from the lead-in trial: Withdrew consent from lead-in trial.
2. Patients rolling over from the lead-in trial: 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. Patients rolling over from the lead-in trial: 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. Patients rolling over from the lead-in trial: 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. Patients rolling over from the lead-in trial: Committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
6. Patients rolling over from the lead-in trial: An employee of the sponsor or Investigator or otherwise dependent on them.
7. Patients screened directly to the Extension Trial: More than 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.
8. Patients screened directly to the Extension Trial: Poorly controlled inflammatory bowel disease (IBD) that is moderately or severely active or fistula interfering with measurements or examinations required in the trial.
9. Patients screened directly to the Extension Trial: Bowel obstruction.
10. Patients screened directly to the Extension Trial: Known radiation enteritis or significant villous atrophy, e.g., due to active celiac disease.
11. Patients screened directly to the Extension Trial: Cardiac disease defined as: decompensated heart failure (New York Heart Association [NYHA] Class III-IV), unstable angina pectoris, and.
12. Patients screened directly to the Extension Trial: Clinically significant abnormal ECG as judged by the Investigator.
13. Patients screened directly to the Extension Trial: Repeated (2 or more consecutive measurements separated by at least 15 minutes) systolic blood pressure measurements > 180 mm Hg.
14. Patients screened directly to the Extension Trial: Human immunodeficiency virus (HIV) positive, acute liver disease, or unstable chronic liver disease.
15. Patients screened directly to the Extension Trial: 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.
16. Patients screened directly to the Extension Trial: Estimated creatinine clearance (CrCL; by the Cockcroft-Gault formula) < 30 mL/min.
17. Patients screened directly to the Extension Trial: 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
18. Patients screened directly to the Extension Trial: Use of GLP-1, GLP-2, HGH, somatostatin, or analogs thereof, within 3 months prior to Screening.
19. Patients screened directly to the Extension Trial: Use of DPP-4 inhibitors within 3 months prior to Screening.
20. Patients screened directly to the Extension Trial: Systemic immunosuppressive therapy that has been introduced or has been unstable within 3 months prior to Screening.
21. Patients screened directly to the Extension Trial: Unstable biological therapy (e.g. anti-tumor necrosis factor alpha [TNF-α], natalizumab, etc.) within 6 months prior to Screening, including significant changes in doses or switch of drug.
22. Patients screened directly to the Extension Trial: 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.
23. Patients screened directly to the Extension Trial: Known or suspected hypersensitivity to glepaglutide or related products.
24. Patients screened directly to the Extension Trial: Previous exposure to glepaglutide.
25. Patients screened directly to the Extension Trial: Previous participation (randomization) in this trial.
26. Patients screened directly to the Extension Trial: Current, or within 30 days prior to Screening, participation in another interventional clinical trial that includes administration of an active compound.
27. Patients screened directly to the Extension Trial: Mental incapacity or language barriers which preclude adequate understanding or cooperation, or unwillingness to comply with trial requirements.
28. Patients screened directly to the Extension Trial: 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.
29. Patients screened directly to the Extension Trial: Committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
30. Patients screened directly to the Extension Trial: An employee of the Sponsor or Investigator or otherwise dependent on them.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 9

1. Safety Endpoints: Incidence and type of AEs (primary endpoint)
2. Safety Endpoints: Incidence and type of serious adverse events (SAEs) and AESIs.
3. Safety Endpoints: Changes from baseline in: - Vital signs -Electrocardiogram (ECG)
4. Safety Endpoints: Changes from baseline in: -Hematology -Biochemistry -Urinalysis
5. Safety Endpoints: Immunogenicity
6. Efficacy Endpoints: Reduction in weekly PS volume from baseline
7. Efficacy Endpoints:Reduction of at least 20% in weekly PS volume from baseline
8. Efficacy Endpoints: Reduction in days on PS ≥ 1 day/week from baseline
9. Efficacy Endpoints: Reduction in weekly PS volume of 100% (weaned off)

Secondary endpoints 5

1. Change in fluid composite effect (FCE) from baseline
2. Reduction in calculated energy content of parenteral macronutrients from baseline
3. Reduction in number of days on PS per week from baseline
4. Reduction of at least 40% in weekly PS volume from baseline
5. Change in weight from baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zealand Pharma A/S

Sponsor organisation

Zealand Pharma A/S

Address

Sydmarken 11

City

Soeborg

Postcode

2860

Country

Denmark

Scientific contact point

Organisation

Zealand Pharma A/S

Contact name

Zealand Pharma

Public contact point

Organisation

Zealand Pharma A/S

Contact name

Zealand Pharma

Locations

5 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 47 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications