A Clinical Study in AGHD to Assess Safety, Tolerability and Efficacy of GX-H9

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02946606
• Date of registration: 28/08/2015
• Prospective Registration: No
• Primary sponsor: Genexine, Inc.
• Public title: A Clinical Study in AGHD to Assess Safety, Tolerability and Efficacy of GX-H9
• Scientific title: 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)
• Date of first enrolment: January 2015
• Target sample size: 45
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02946606
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Korea, Republic of

Contacts

• Name: Eun Jig Lee, MD, PhD
• Affiliation: Yonsei University

Key inclusion & exclusion criteria

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 growth hormone (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 standard deviation (SD) score (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-recombinant human growth hormone
(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 6 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.

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.



Age minimum: 20 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Adult Growth Hormone Deficiency

Intervention(s)

Drug: Genotropin

Drug: GX-H9

Primary Outcome(s)

The change in insulin-like growth factor-1 (IGF-1) levels in relation to time and dose strength [Time Frame: 12 weeks]

Secondary Outcome(s)

Immunogenicity Test After subcutaneous injection of GX-H9 [Time Frame: 12 weeks]

PD profile of GX-H9 in the treatment of AGHD: Maximum serum concentration of IGFBP-3, Cmax [Time Frame: 12 weeks]

Pharmacodynamic (PD) profile of GX-H9 in the treatment of AGHD: Maximum serum concentration of IGF-1, Cmax [Time Frame: 12 weeks]

PK profile of GX-H9 in the treatment of AGHD: Area under the curve, AUC0-inf [Time Frame: 12 weeks]

The lipid parameters as actual values and percent change from baseline (CFB) at week 12: low-density lipoprotein cholesterol [Time Frame: change from baseline at 12weeks]

Data in Physical examination, Vital signs, Electrocardiography, Clinical Laboratory Test Results Related to Investigational Product [Time Frame: 12 weeks]

Pharmacokinetic (PK) profile of GX-H9 in the treatment of AGHD: Area under the curve, AUC0-t [Time Frame: 12 weeks]

PK profile of GX-H9 in the treatment of AGHD: Area under the curve, AUC0-tau [Time Frame: 12 weeks]

PK profile of GX-H9 in the treatment of AGHD: Half-life, t1/2 [Time Frame: 12 weeks]

The changes of glucose metabolism indices [Time Frame: 12 weeks]

PK profile of GX-H9 in the treatment of AGHD: Maximum serum concentration, Cmax [Time Frame: 12 weeks]

The lipid parameters as actual values and percent change from baseline (CFB) at week 12: High-density lipoprotein cholesterol [Time Frame: change from baseline at 12weeks]

PD profile of GX-H9 in the treatment of AGHD: Area under curve of IGF-1, AUC0-t [Time Frame: 12 weeks]

PK profile of GX-H9 in the treatment of AGHD: The time taken to reach the maximum concentration, Tmax [Time Frame: 12 weeks]

The waist-to-hip ratio as actual values and CFB at week 12 [Time Frame: change from baseline at 12weeks]

The BMI as actual values and CFB at week 12 [Time Frame: change from baseline at 12weeks]

The lipid parameters as actual values and percent change from baseline (CFB) at week 12: lipoprotein[a] [Time Frame: change from baseline at 12weeks]

The waist circumference as actual values and CFB at week 12 [Time Frame: change from baseline at 12weeks]

PD profile of GX-H9 in the treatment of AGHD: Area under curve of IGFBP-3, AUC0-t [Time Frame: 12 weeks]

The hip circumference as actual values and CFB at week 12 [Time Frame: change from baseline at 12weeks]

Data in hormonal status of thyroid, estradiol(female), testosterone(male), and cortisol levels [Time Frame: 12 weeks]

The lipid parameters as actual values and percent change from baseline (CFB) at week 12: Triglycerides [Time Frame: change from baseline at 12weeks]

The lipid parameters as actual values and percent change from baseline (CFB)at week 12: total cholesterol [Time Frame: change from baseline at 12weeks]

Secondary ID(s)

GX-H9-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors