Clinical Trials Register

Summary
EudraCT Number:	2021-000176-11
Sponsor's Protocol Code Number:	HM-GLP2-201
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-07-07
Trial 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

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-000176-11

A.3

Full title of the trial

A Multicenter, Proof-of-concept, Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HM15912 in Adult Subjects with Short Bowel Syndrome-associated Intestinal Failure (SBS-IF) (DOLPHINS-2)

A.3.1

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

Study of HM15912 in subjects with Short Bowel Syndrome-associated Intestinal Failure

A.3.2

Name or abbreviated title of the trial where available

DOLPHINS-2

A.4.1

Sponsor's protocol code number

HM-GLP2-201

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04775706

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	Hanmi Pharm. Co., Ltd.
B.1.3.4	Country	Korea, Republic of
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	Hanmi Pharm. Co., Ltd.
B.4.2	Country	Korea, Republic of
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hanmi Pharm. Co., Ltd.
B.5.2	Functional name of contact point	Chief Medical Officer's Office
B.5.3	Address:
B.5.3.1	Street Address	14, Wiryeseong-daero, Songpa-gu
B.5.3.2	Town/ city	Seoul
B.5.3.3	Post code	05545
B.5.3.4	Country	Korea, Republic of
B.5.4	Telephone number	+822 410 9039
B.5.6	E-mail	seungjae.baek@hanmi.co.kr

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/18/2126
D.3 Description of the IMP
D.3.1	Product name	HM15912 (LAPS GLP-2 analog)
D.3.2	Product code	HM15912 (LAPS GLP-2 analog)
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	Human glucagon-like peptide-2 analogue linked to a human immunoglobulin Fc fragment
D.3.9.2	Current sponsor code	HM15912
D.3.9.3	Other descriptive name	Human glucagon-like peptide-2 analogue linked to a human immunoglobulin Fc fragment
D.3.9.4	EV Substance Code	SUB193715
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	125
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)	Yes
	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	No
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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

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-associated Intestinal Failure (SBS-IF)

E.1.1.1

Medical condition in easily understood language

Short bowel length. With intestinal failure, the length and function of the small intestine falls below the minimum necessary for the absorption of nutrients and water to maintain good health.

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

Primary Objectives:
1) To assess safety and tolerability of HM15912 after multiple subcutaneous (SC) doses for 24 weeks
2) To assess the pharmacokinetic (PK) profile of HM15912

E.2.2

Secondary objectives of the trial

To assess the pharmacodynamic (PD) profile of HM15912

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men or women, aged 18 years of age or older with intestinal failure resulting in SBS at the time of
signing the informed consent form (ICF) (or country’s legal age of majority if the legal age is
<18 years)
2. Capable of giving signed informed consent which includes compliance with the requirements and
restrictions listed in the ICF and in this protocol
3. Diagnosis of SBS defined as remaining small bowel in continuity of estimated <200 cm (equal to 79
inches) and with the latest intestinal resection being at least 6 months prior to Screening and
considered stable regarding the PN/IV need. No restorative surgery planned in the study period.
4. Require PN/IV at least 3 days per week for at least 12 months
5. Are willing to adhere to an individual predefined drinking menu during 48-hours recording periods
6. Have no colon polyps or had colon polyps removed by colonoscopy within 6 months prior to
Screening
7. (Only for the subjects who have a remnant part of colon). Not connected to the passage of foods and thereby dormant, can have an
abdominal ultrasound, computerized tomography (CT) scan, or magnetic resonance imaging (MRI)
instead of colonoscopy (if standard of care at site), at the discretion of the Investigator.
Note: If the subject has undergone an upper GI with small bowel follow-through or an abdominal
ultrasound within 6 months before Screening, those test results will be acceptable for the screening
assessments. If the subject has not had these procedures within the 6 months before Screening, then
the procedures will be performed any time after providing informed consent with the results available
and reviewed before Day -1.
8. Have a stoma and able to separate stool and urine during the 48-hour measuring intervals
9. If the subject is not naïve to treatment with GLP-2 analog, the subject may be enrolled if all the
following criteria are met:
a. The duration of discontinuation of GLP-2 analog treatment should be at least 3 months prior
to Screening
b. Willing to provide medical history and/or record to recognize any medically significant
events during previous GLP-2 analog treatment
10. Have body weight ≥30 kg and body mass index (BMI) >18 kg/m2
11. Have at least 12 weeks of clinical remission of Crohn's disease (CD) prior to dosing as demonstrated
by clinical assessment (e.g. Crohn's Disease Activity Index [CDAI], Harvey-Bradshaw Index [HBI])
12. Have stable body weight during the last 3 months prior to Screening (±5% variations allowed)
13. Sexually active female subjects of child-bearing potential must use medically acceptable methods of
birth control during the study and up to 60 days after the last dose of study drug (see Section 8.3.5 for
a list of acceptable birth control methods)
14. Sexually active male subjects must use medically acceptable methods of birth control during the study
and up to 60 days after the last dose of study drug (see Section 8.3.5 for a list of acceptable birth
control methods)

E.4

Principal exclusion criteria

1. Any history of colon cancer.
2. 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 for at least 5 years
3. History of alcohol or drug abuse (within 1 year of screening)
4. Current participation in another study of an investigational agent or investigational device (catheter
lock trials are allowed) within 4 weeks prior to the signing the ICF
5. Have a body weight >100 kg
6. Have no clinically significant abnormal ECG findings (e.g., QTcF > 450 msec for males, QTcF> 470 msec for females, left bundle branch block) that, in the opinion of the Investigator, may interfere with any aspect of study conduct or interpretation of results
7. Have repeated (2 or more consecutive measurements separated by at least 15 minutes) systolic blood pressure (BP) measurements ≥140 mm Hg.
8. Have a hospital admission within 1 month prior to Screening visit
9. Females who are pregnant, breastfeeding, or expect to become pregnant within the projected duration
of the study, starting with the Screening visit through 60 days after the final dose of study drug
10. Males who plan to father children within the projected duration of the study, starting with the
Screening visit through 60 days after the final dose of study drug
11. Have any of the following conditions:
a. Radiation enteritis,
b. Scleroderma,
c. Celiac disease (based on the review of medical history; subjects with normalized antibodies
and histology can be considered for enrollment),
d. Refractory/tropical sprue,
e. Pseudo-obstruction,
f. Active inflammatory bowel disease (IBD) [see inclusion criterion 11],
g. Pre-malignant/malignant change in colonoscopy biopsy or polypectomy,
h. Surgery scheduled during the study period,
i. Positive Human immunodeficiency virus (HIV) test,
j. Positive hepatitis B or C test,
k. Positive syphilis test,
l. Unstable immunological disorders such as rheumatoid arthritis or ulcerous colitis (If the
Investigator would like to enroll a subject with immunological disorders, he/she should
discuss this with the Sponsor and Medical Monitor before enrollment),
m. Significant, active, uncontrolled, untreated systemic diseases
12. Have unstable Crohn’s disease (CD) expected it to worsen over the course of the study and that
required initiation of treatment with biological therapy within 6 months prior to Screening
Note: Subjects treated with stable (unchanged dosage) of immunosuppressant therapy and biological
therapy are eligible for enrollment in the study.
13. Have IBD that required chronic systemic immunosuppressant therapy that had been introduced or
changed during the 3 months prior to Screening
14. Have unstable biological therapy (e.g., anti-tumor necrosis factor (TNF)-α, natalizumab, etc.) within 6
months prior to Screening, including significant changes in doses or switch of drug
15. Have unstable absorption due to cystic fibrosis or known deoxyribonucleic acid (DNA) abnormalities
(e.g., familial adenomatous polyposis, Fanconi-Bickel syndrome)
16. Have more than 4 hospitalizations related to PN/IV volume adjustments within 12 months of
Screening
17. Are not expected to be amenable to oral or tube feeding regimens
18. Have cardiac disease defined as decompensated heart failure (New York Heart Association Class IV),
unstable angina pectoris, and/or myocardial infarction within the last 6 months prior to screening
19. Have estimated creatinine clearance (CrCl; by the Cockcroft-Gault formula) <60 mL/min
20. Clinically significant laboratory abnormalities at the time of Screening, defined as having any of the
following:
a. Platelet count < 100 × 103/µL
b. White blood cells < 3.5 × 103/µL
c. Neutrophils < 1.5 × 103/µL
d. Hemoglobin levels < 8 g/dL
21. Persistent hepatic impairment defined by 2 of the following laboratory tests meeting the criteria
below. Repeat tests done within 2 weeks apart must confirm the results.
e. Total bilirubin ≥2 × the upper limit of normal (ULN), or
f. Aspartate aminotransferase (AST) ≥5 × ULN, or
g. Alanine aminotransferase (ALT) ≥5× ULN
22. Have any use of GLP-1, dipeptidyl peptidase 4 (DPP-4) inhibitor, growth hormone, glutamine, or
analogs thereof within 3 months prior to Screening
23. Subject deemed by the Principal Investigator to be inappropriate for participation in the study (e.g.,
any condition or circumstance which, in the Investigator's opinion, would put the subject at any undue
risk, prevent completion of the study, or interfere with analysis of the study results)

E.5 End points

E.5.1

Primary end point(s)

1) Primary endpoints to "assessment of safety and tolerability of HM15912 after multiple subcutaneous (SC) doses for 24 weeks:
• Incidence of adverse events (AEs)
• Incidence of injection site reactions
• Incidence of clinical laboratory abnormalities
• Clinically significant findings on physical examination
• Changes from baseline in vital signs and 12-lead
electrocardiogram (ECG) parameters

2) Primary endpoints to "assessment of the pharmacokinetic (PK) profile of HM15912":
• Maximum plasma concentration (Cmax)
• Time to maximum plasma concentration (tmax)
• Elimination half-life (t1/2)
• Volume of distribution (Vd)
• Clearance (CL)
• Area under the concentration-time curve from time zero to the
last observable concentration (AUC0-t), and AUC extrapolated
to infinity (AUC0-∞)

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout trial treatment/follow-up period.

E.5.2

Secondary end point(s)

• Change in weekly parenteral nutrition/intravenous fluid (PN/IV) volume from baseline to Week 25
Note: The baseline PN/IV volume (L/week) is the average of actual PN/IV volume received during the last 2 weeks of the Stabilization period.

E.5.2.1

Timepoint(s) of evaluation of this end point

For time-point(s) see section E.5.2.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Open label extension (only study drug); Next dose level will be submitted as an amendment.

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

France

Germany

Poland

E.8.7

Trial has a data monitoring committee

Yes

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

A subject will be considered as having completed the study when:
• Subject completes the Week 53 Visit
OR
• Subject completes the Follow-up Visit

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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)

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

The investigator is responsible for ensuring that consideration has been given to the post- trial care of the subject's medical condition.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Medical Research Network (MRN)
G.4.3.4	Network Country	United Kingdom

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-09-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-07-01

P. End of Trial
P.	End of Trial Status	Ongoing

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