A Phase 2, Randomized, Open-label, Active Controlled, Dose Finding Study of Long-acting Hybrid Fc Fused Recombinant Human Growth Hormone (GX-H9) in Paeditaric Patients With Growth Hormone Deficiency
Overview
- Phase
- Phase 2
- Intervention
- GX-H9
- Conditions
- Growth Hormone Deficiency
- Sponsor
- Genexine, Inc.
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Annual height velocity in cm/year
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Detailed Description
GX-H9 is a new hGH product fused to hybrid Fc in studies as a once-a-week and every other week dosing regimen designed to overcome the inconvenience of daily rhGH injections and is under the studies designed to determine if the safety profile is comparable to currently approved daily rhGH products. Obviating the need for daily injections may increase compliance and therefore efficacy, which would be of great benefit to both paediatric and adult patients with GHD and other disorders with associated growth impairment and need for hGH substitution.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
- •Annualized height velocity (HV) of at least 1 SD below the mean HV for chronological age and gender according to the standards of Prader et al (1989). The interval between two height measurements should be at least 6 months (but not longer than 18 months) before inclusion
- •All subjects must have at least one cranial imaging study \[magnetic resonance imaging (MRI) or computed tomography (CT)\] prior to randomization:
Exclusion Criteria
- •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
Arms & Interventions
Cohort 3
GX-H9 subcutaneous injections (twice-monthly)
Intervention: GX-H9
Cohort 1
GX-H9 subcutaneous injections (weekly)
Intervention: GX-H9
Cohort 2
GX-H9 subcutaneous injections (weekly)
Intervention: GX-H9
Cohort 4
Genotropin subcutaneous injections (daily)
Intervention: Genotropin
Outcomes
Primary Outcomes
Annual height velocity in cm/year
Time Frame: 6 months
The primary efficacy variable was the AHV in cm/year at 6 months.
Secondary Outcomes
- Annualized Height velocity expressed in SDS(3, 6, 12 and 24 months)
- Bone maturation after 12 and 24 months of treatment;(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 IGF-I SDS(25 months)
- Predicted adult height change from start to 12 and 24 months(12 and 24 months)
- Change in height expressed in cm(3, 6, 12 and 24 months)
- Change in absolute IGF-I levels(25 months)
- Change in absolute IGFBP-3 levels(25 months)
- Change in IGFBP-3 SDS(25 months)
- Number of subjects needing at least one dose modification(25 months)