Dose Finding Study of GX-H9 in Paeditaric Patients With Growth Hormone Deficiency

NCT03309891 | Completed Phase 2 DMC

• 1 other identifier: GX-H9-003
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, active controlled, Phase 2 study designed to assess the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of weekly and semi-monthly doses of GX-H9 in the treatment of Paediatric Growth Hormone Deficiency (PGHD) as compared to the standard of care daily rhGH treatment.

Conditions

Growth Hormone Deficiency

Outcome Measures

Primary Outcomes (1)

• Annual height velocity in cm/year

  The primary efficacy variable was the AHV in cm/year at 6 months.

  6 months

Secondary Outcomes (11)

• Annualized Height velocity expressed in SDS

  3, 6, 12 and 24 months

• Change in height SDS (compared to baseline value)

  3, 6, 12 and 24 months

• Annualized height velocity expressed in cm/year

  3, 12 and 24 months

• Change in height expressed in cm

  3, 6, 12 and 24 months

• Change in absolute IGF-I levels

  25 months

Study Arms (4)

Cohort 1

EXPERIMENTAL

GX-H9 subcutaneous injections (weekly)

Drug: GX-H9

Cohort 2

EXPERIMENTAL

GX-H9 subcutaneous injections (weekly)

Drug: GX-H9

Cohort 3

EXPERIMENTAL

GX-H9 subcutaneous injections (twice-monthly)

Drug: GX-H9

Cohort 4

ACTIVE COMPARATOR

Genotropin subcutaneous injections (daily)

Drug: Genotropin

Interventions

GX-H9 DRUG

subcutaneous injection (weekly or twice-monthly)

Cohort 1; Cohort 2; Cohort 3

Genotropin DRUG

subcutaneous injection (daily)

Cohort 4

Eligibility Criteria

• Age: 3 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pre-pubertal children with either isolated GHD, or GH insufficiency as part of multiple pituitary hormone insufficiency, idiopathic or organic GH insufficiency (e.g., due to pituitary tumor, pituitary or brain surgery):
• Boys: 3 years ≤ boy's age ≤ 11 years
• Girls: 3 years ≤ girl's age ≤ 10 years
• GHD confirmed by 2 different GH provocation tests with peak GH concentration below 10 ng/mL as described in consensus guidelines. Well documented historical GH provocation tests can be used for study eligibility providing that the tests are performed as defined in Appendix 2 (e.g. the same sampling time points). Data of each historical GH stimulation test will be reviewed by Medical Monitor and Sponsor in order to assess acceptance for the study
• Without prior exposure to any rhGH therapy
• Bone age (BA) is not older than chronological age and should not be greater than 9 years for girls and 10 years for boys
• Impaired height and height velocity defined as:
• Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age (CA) and gender according to the standards from Prader et. al 1989, (HT SDS ≤ -2.0)
• All subjects must have at least one cranial imaging study \[magnetic resonance imaging (MRI) or computed tomography (CT)\] prior to randomization:
• To exclude intracranial causes of GHD in subjects without history of pituitary tumor \[obtained within 6 months prior to informed consent signing, or
• Subjects with a previously treated pituitary tumor must have no tumor progression for at least the past year \[obtained within 3 months prior to informed consent signing, compared with a previous MRI or CT performed at least 12 months earlier\]
• If not performed within these specified time frames prior to informed consent signing, may be performed as a part of the screening procedures
• Body mass Index (BMI) must be within ±2 SD of mean BMI for the chronological age and sex according to the 2000 CDC standards
• Baseline IGF-1 level of at least 1 SD below the mean IGF-1 level standardized for age and sex (IGF-1 SDS≤ -1.0) according to the central laboratory reference values. One IGF-1 retest is allowed during the Screening period if first results were not higher than
• SDS and if GH stimulation tests results and auxology parameters met eligibility criteria

You may not qualify if:

• History of radiation therapy or chemotherapy
• Malnourished children defined as:
• Serum albumin below the lower limit of normal (LLN) according to the reference ranges of central laboratory; and
• Serum iron below the lower limit of normal (LLN) according to the reference ranges of central laboratory; and
• BMI\<-2 SD for age and sex
• Children with psychosocial dwarfism
• Children born small for gestational age (SGA-birth weight and/or birth length \< -2 SD for gestational age according to the standards from Niklasson et al., 1991)
• Presence of anti-hGH antibodies at screening
• Any clinically significant abnormality likely to affect growth or the ability to evaluate growth, such as, but not limited to, chronic diseases like renal insufficiency, spinal cord irradiation, etc.
• Subjects with diabetes mellitus
• Subjects with impaired fasting sugar (based on WHO; fasting blood sugar \> 110mg/dl or 6.1 mmol/l) after repeated blood analysis
• Chromosomal abnormalities and medical syndromes (Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, SHOX mutations/deletions and skeletal dysplasias), with the exception of septo-optic dysplasia
• Evidence of closed epiphyses
• Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids and methylphenidate for attention deficit hyperactivity disorder (ADHD), with the exception of hormone replacement therapies \[thyroxine, hydrocortisone, desmopressin (DDAVP)\]
• Children requiring glucocorticoid therapy, other than treated for hypothalamo-pituitary-adrenal insufficiency in replacement doses who are taking a dose of greater than 400 μg/d of inhaled budesonide or equivalents for longer than 1 month during a calendar year (e.g. asthma)

Sponsors & Collaborators

• Genexine, Inc.: lead

Study Sites (1)

Odessa National Medical University, Odessa Regional Children's Hospital

Odesa, Ukraine

Location

MeSH Terms

Conditions

Dwarfism, Pituitary

Interventions

GX-H9; Human Growth Hormone

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jungwon Woo

  Genexine, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase 2, randomized, open-label, active controlled, dose finding study

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: October 16, 2017
• Study Start: January 18, 2016
• Primary Completion: October 27, 2017
• Study Completion: May 15, 2019
• Last Updated: April 20, 2020

Record last verified: 2020-04

Locations

UA (1)