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

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2014-002698-13-DE
• Date of registration: 23/12/2014
• Prospective Registration: Yes
• 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: 11/06/2015
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002698-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Genotropin® Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Greece, Hungary, Korea, Republic of, Poland, Serbia, Slovakia, Sweden

Contacts

• Name: Emily Merrell
• Affiliation: PPD

• Name: Emily Merrell
• Affiliation: PPD

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 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 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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. 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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Adult Growth Hormone Deficiency (AGHD)
MedDRA version: 18.1 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Name: GX-H9
Pharmaceutical Form: Solution for injection
Current Sponsor code: GX-H9
Other descriptive name: hGH-hyFc, recombinant human growth hormone
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Trade Name: Genotropin®
Product Name: Genotropin®
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: somatropin
CAS Number: 12629-01-5
Current Sponsor code: Genotropin®
Other descriptive name: recombinant DNA-derived human growth hormone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12-

Primary Outcome(s)

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

Primary end point(s): The primary endpoint will be the change in serum IGF-1 levels in relation to time and dose strengths.

Secondary Objective: •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.

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

Secondary Outcome(s)

Secondary end point(s): The secondary PK endpoints will be PK parameters, including AUC0-t, AUC0 inf, AUC0-tau, Cmax, Tmax, and t1/2.

Timepoint(s) of evaluation of this end point: first and last week of treatment.

Secondary ID(s)

GX-H9-002

2014-002698-13-SK

Source(s) of Monetary Support

Genexine, Inc