Clinical Trials Register

Summary
EudraCT Number:	2014-002698-13
Sponsor's Protocol Code Number:	GX-H9-002
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-03-17
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

Greece - EOF

A.2

EudraCT number

2014-002698-13

A.3

Full title of the trial

A randomized, active-controlled, multiple-dose, open-label study to evaluate the safety, tolerability, and efficacy of the long-acting antibody-fused recombinant human growth hormone (GX-H9) in adult growth hormone deficiency (AGHD)

A.3.1

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

A clinical study in AGHD to assess safety, tolerability and efficacy of GX-H9

A.4.1

Sponsor's protocol code number

GX-H9-002

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	Genexine, Inc
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	Genexine, Inc
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	PPD
B.5.2	Functional name of contact point	Matthias Oleszewski
B.5.3	Address:
B.5.3.1	Street Address	Hansastr. 32
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	80686
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 62 336 50 174
B.5.5	Fax number	+49 89 578 77 400
B.5.6	E-mail	Matthias.Oleszewski@ppdi.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	GX-H9
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.3.9.2	Current sponsor code	GX-H9
D.3.9.3	Other descriptive name	hGH-hyFc, recombinant human growth hormone
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	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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	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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Genotropin®
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Genotropin®
D.3.4	Pharmaceutical form	Powder and solvent for 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	somatropin
D.3.9.1	CAS number	12629-01-5
D.3.9.2	Current sponsor code	Genotropin®
D.3.9.3	Other descriptive name	recombinant DNA-derived human growth hormone
D.3.9.4	EV Substance Code	SUB10584MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	12
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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	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

Adult Growth Hormone Deficiency (AGHD)

E.1.1.1

Medical condition in easily understood language

Lack of growth hormone in the body

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10056438
E.1.2	Term	Growth hormone deficiency
E.1.2	System Organ Class	10014698 - Endocrine disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To evaluate the change in insulin-like growth factor-1 (IGF-1) levels in relation to time and dose strengths

E.2.2

Secondary objectives of the trial

•To assess the PK and PD profiles of long acting antibody fused rhGH (GX-H9) in the treatment of AGHD.
•To evaluate the safety and tolerability of GX-H9 in the treatment of AGHD.
•To assess the lipid parameters (total cholesterol, high density lipoprotein cholesterol [HDL C], low density lipoprotein cholesterol [LDL C], triglycerides, lipoprotein[a]) as actual values and percent CFB at Week 12.
•To assess the waist circumference as actual values and CFB at Week 12.
•To assess the hip circumference as actual values and CFB at Week 12.
•To assess the waist-to-hip ratio as actual values and CFB at Week 12.
•To assess the body mass index (BMI) as actual values CFB at Week 12.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each subject must meet all of the following criteria to be enrolled in this study:
1. Is a male or female aged ≥20 and ≤ 65 years with AGHD, either adult onset GHD due to hypothalamic pituitary disease or childhood onset GHD that is either idiopathic or due to hypothalamic pituitary disease or due to genetic causes.
2. Has documented confirmation (medical history) of GH deficiency during adulthood by 1 or more GH stimulation tests, as follows:
• Insulin tolerance test (peak hGH≤3.0 ng/mL)
• Arginine + growth-hormone-releasing hormone (peak hGH≤4.0 ng/mL)
3. Has been treated with stable hormonal replacement therapies for deficiencies of other hypothalamo pituitary axes and must have been on an optimized and stable treatment regimen for at least 3 months before screening (free thyroxine [T4] level within normal range at screening). Temporary adjustment of glucocorticoid replacement therapy, as appropriate, is acceptable.
4. Has a screening IGF-1 level of at least 1 SD (IGF-1 SD score <-1) below the mean IGF 1 level standardized for age and gender according to the central laboratory reference values.
5. Has a BMI of ≥18.0 and ≤ 35.0 kg/m2 (both male and female subjects).
6. Has a confirmed negative test result for anti-rhGH antibodies at screening.
7. Must agree to use appropriate contraceptive methods (ie, condoms, cervical cap in conjunction with spermicide, sterilization, and intra uterine device) during the study and for 3 months after the last dose of study drug.
8. Female subjects must have a negative serum pregnancy test result at screening.
9. Must be willing and able to provide written informed consent before performing any study procedures.

E.4

Principal exclusion criteria

A subject meeting any of the following criteria will be excluded from the study:
1. Has evidence of growth of pituitary adenoma or other intracranial tumor within the last 12 months which has to be confirmed by computed tomography or magnetic resonance imaging scan (with contrast) within 3 months before screening. (Subjects with inactive remnant intracranial tumors are eligible).
2. Is currently receiving antitumor therapy and has a history of malignancy other than i) cranial tumor or leukemia causing GHD, or ii) fully treated basal cell carcinoma or evidence of active malignancy.
3. Has any clinically significant electrocardiogram (ECG) abnormality at screening.
4. Has evidence of intracranial hypertension at screening.
5. Has uncontrolled diabetes mellitus with diet and exercise, as determined based on glycated hemoglobin (HbA1c) levels ≥7.0% at screening.
6. Has impaired liver function defined as elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.0 × upper limit of normal (ULN).
7. Has impaired kidney function defined as increased serum creatinine levels greater than 1.5 × ULN.
8. Has had active acromegaly within 18 months before screening.
9. Has active carpal tunnel syndrome.
10. Has Prader-Willi syndrome.
11. Has had active Cushing syndrome within 12 months before screening.
12. Has any other major medical conditions, including eg, clinically manifested hypertension, tuberculosis, major surgery within the 3 months before screening, or significantly abnormal laboratory test results (eg, disturbed calcium homeostasis); or any other conditions (eg, acute infections) that may influence drug absorption, metabolism, or excretion, or that may interfere with any study variables in the judgment of the investigator.
13. Has been treated with systemic corticosteroids other than replacement therapy within 3 months before screening.
14. Is a female subject of childbearing potential who is pregnant, breastfeeding, or intends to become pregnant.
15. Has been treated with anabolic steroids other than gonadal steroid-replacement therapy within 2 months before screening. Oral estrogen replacement and hormonal contraceptives are not allowed in female subjects. For replacement purposes, transdermal estrogens are permitted in female subjects.
16. Has a history of noncompliance with medications, uncooperativeness, or alcohol/drug abuse.
17. Has a positive result from serology examination for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
18. Has a known or suspected hypersensitivity to rhGH.
19. Has donated blood or had any major blood loss greater than 500 mL within 90 days before screening.
20. Has a history of any medical or psychiatric condition that in the opinion of the investigator would pose a risk for participation in this study or interfere with the compliance needed for this study.
21. Has received an investigational drug or product or has participated in a drug study within 60 days before screening.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the change in serum IGF-1 levels in relation to time and dose strengths.

E.5.1.1

Timepoint(s) of evaluation of this end point

The serum IGF-1 levels will be assessed as following time points:
•Subjects receiving 0.1 and 0.3 mg protein/kg GX-H9 weekly and 6 μg/kg Genotropin® daily: On Day 4 (72 hours after dosing, +1 day visit window) at Weeks 1, 3, 5, 7, 9, 11 and 12
•Subjects receiving 0.3 and 0.6 mg protein/kg GX-H9 every other week: On Day 4 (72 hours after dosing, +1 day visit window) at Weeks 1, 3, 5, 7, 9 and 11

E.5.2

Secondary end point(s)

The secondary PK endpoints will be PK parameters, including AUC0-t, AUC0 inf, AUC0-tau, Cmax, Tmax, and t1/2.

E.5.2.1

Timepoint(s) of evaluation of this end point

first and last week of treatment.

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

Yes

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)

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

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

Yes

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.3.1

Comparator description

Genotropin®

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

France

Germany

Greece

Hungary

Korea, Republic of

Poland

Serbia

Slovakia

Sweden

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

The end of the study is defined as the date on which the last subject completes the last visit (includes 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)

None - Patient will continue on normal standard of care

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

2015-02-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-12-30

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