Clinical Trials Register

Summary
EudraCT Number:	2020-005194-27
Sponsor's Protocol Code Number:	ZP1848-20060
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2020-005194-27

A.3

Full title of the trial

A Single-Center Phase 3b Trial Investigating the Long-term Effect on Intestinal
Absorption, Nutritional Status and Long-Term Safety of treatment with Glepaglutide in Patients
with Short Bowel Syndrome (SBS)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

The long-term effect on intestinal absorption and safety of treatment with
Glepaglutide in patients with short bowel syndrome

A.3.2

Name or abbreviated title of the trial where available

EASE SBS 4

A.4.1

Sponsor's protocol code number

ZP1848-20060

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1260-2961

A.5.4

Other Identifiers

Name:

IND

Number:

133151

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Zealand Pharma A/S
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Zealand Pharma A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Zealand Pharma A/S
B.5.2	Functional name of contact point	Mikkel Askjær Agersnap
B.5.3	Address:
B.5.3.1	Street Address	Sydmarken 11
B.5.3.2	Town/ city	Søborg
B.5.3.3	Post code	DK-2860
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+455060 3869
B.5.6	E-mail	MAgersnap@zealandpharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Glepaglutide
D.3.2	Product code	ZP1848
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GLEPAGLUTIDE
D.3.9.1	CAS number	914009-86-2
D.3.9.2	Current sponsor code	ZP1848
D.3.9.4	EV Substance Code	SUB192388
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Short bowel syndrome

E.1.1.1

Medical condition in easily understood language

Short gut

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10049416
E.1.2	Term	Short-bowel syndrome
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To demonstrate the 24-week effect
of glepaglutide on the absorption of
fluids.

E.2.2

Secondary objectives of the trial

1. To assess the effects of
glepaglutide on absorption of energy,
absorption of the individual
macronutrients and absorption of
electrolytes.
2. To evaluate the long-term
efficacy of glepaglutide in patients
with SBS.
3. To describe the long-term safety
of glepaglutide.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent obtained before any trial-related activities. Trial-related activities are any
procedures that are carried out as part of the trial, including activities to determine suitability
for the trial.
2. Age ≥ 18 years and ≤ 90 years at screening.
3. Willing to comply with trial procedures, including 2 in-house visits with urine and fecal
output collection.
4. Stable condition of SBS either with intestinal failure (IF) or intestinal insufficiency. For
patients with SBS-IF a stable condition is defined as < 25% change in PS volume or energy
content for 4 weeks prior to screening.
5. Stable body weight (<5% change in weight in the 3 months prior to screening).
6. Wet weight of fecal excretion ≥1,500 g/day demonstrated during a hospital stay prior to
screening*.
*If inclusion criteria #6 cannot be met, a visit may be scheduled where fecal output collected at
home by the patient or during a hospital stay can be assessed. If the wet weight of fecal excretion
≥1,500 g/day can be demonstrated, the criterion #6 is met.

E.4

Principal exclusion criteria

General
1. Current, or within 30 days prior to screening, participation in another interventional clinical
trial that includes administration of an active compound.
2. Mental incapacity or language barriers which preclude adequate understanding or
cooperation, or unwillingness to comply with trial requirements.
3. Previous participation in this trial. Participation is defined as having received trial product.
4. Females of childbearing potential, who are pregnant, breast-feeding, intend to become
pregnant or are not using highly effective contraceptive methods. Male patients with female
partners, who intend to become pregnant.

Medical history and concomitant diseases
5. 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.
6. Poorly controlled inflammatory bowel disease (IBD) that is moderately or severely active or
fistula interfering with measurements or examinations required in the trial.
7. Current bowel obstruction.
8. Known radiation enteritis or significant villous atrophy, e.g., due to active celiac disease.
9. Cardiac disease defined as: decompensated heart failure (New York Heart Association
[NYHA] Class III-IV), unstable angina pectoris, and/or myocardial infarction within the last
6 months prior to screening.
10. Clinically significant abnormal electrocardiogram (ECG) as judged by the Investigator.
11. Human immunodeficiency virus (HIV) positive, acute liver disease including positive results
for Hepatitis B antigens (HBsAg) and Hepatitis C (HCV), or unstable chronic liver disease.
12. 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.
13. 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
14. Use of GLP-1, GLP-2, human growth hormone (HGH), somatostatin, or analogs thereof,
within 3 months prior to screening.
15. Known or suspected hypersensitivity to glepaglutide, its components or related products.
16. Use of dipeptidyl peptidase (DPP)-4 inhibitors within 3 months prior to screening.
17. Surgical resection of gut tissue within 6 months prior to screening.
18. Systemic immunosuppressive therapy for treatment of the gastrointestinal tract that has been
introduced or has been unstable within 3 months prior to screening.
19. Unstable biological therapy (e.g. anti-TNF-α, natalizumab, etc.) within 6 months prior to
screening, including significant changes in doses or switch of drug.

E.5 End points

E.5.1

Primary end point(s)

1. Absorption of wet weight/fluids: Change from baseline to
Week 24 assessed by 48-hour metabolic balance studies.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 0 (baseline) and week 24

E.5.2

Secondary end point(s)

1. Absorption of energy (oral intake minus fecal excretion):
Change from baseline to Week 24 measured by 48-hour
metabolic balance studies. Energy absorption is measured by
bomb calorimetry.
Secondary efficacy endpoints:
2. Absorption of individual macronutrients (carbohydrates,
lipids and proteins): Change from baseline to Week 24
measured by 48-hour metabolic balance studies.
3. Absorption of electrolytes (sodium, potassium, calcium
and magnesium): Change from baseline to Week 24
measured by 48-hour metabolic balance studies.
For patients with SBS-IF only:
4. Weekly PS volume: Change from baseline to Week 12 and
24.
5. Weekly PS macronutrients (carbohydrates, lipids and
proteins) and electrolytes (sodium, potassium and
magnesium): Change from baseline to Week 12 and 24.
Safety endpoints:
6. Treatment-emergent AEs until follow-up at Week 56.
7. Immunogenicity (anti-glepaglutide antibodies, reactivity to
ZP18481-34, cross-reactivity to glucagon-like peptide [GLP]-
2, glepaglutide neutralizing antibodies) at baseline (W0),
Week 4, 12, 24, 52, and 56.

E.5.2.1

Timepoint(s) of evaluation of this end point

From week 0 to week 56 (visit 1-12 plus follow up)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-09-05

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