A Phase 3 Trial of the Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)

Study Overview
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Brief Summary
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A 52 week trial of TransCon hGH, a long-acting growth hormone product, versus human growth hormone therapy. TransCon hGH will be given once-a-week, human growth hormone (hGH) will be given daily. Approximately 150 prepubertal, hGH-treatment naïve children (males and females) with GHD will be included. Randomization will occur in a 2:1 ratio (TransCon hGH : Genotropin). This is a global trial that will be conducted in Armenia, Australia, Belarus, Bulgaria, Georgia, Greece, Italy, New Zealand, Poland, Romania, Russia, Turkey, Ukraine, and the United States.

Official Title
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A Multicenter, Phase 3, Randomized, Open-label, Active-controlled, Parallel-group Trial Investigating the Safety, Tolerability, and Efficacy of TransCon hGH Administered Once a Week Versus Standard Daily hGH Replacement Therapy Over 52 Weeks in Prepubertal Children With Growth Hormone Deficiency (GHD)

Conditions
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hGH (Human Growth Hormone), Growth Hormone Deficiency, Pediatric, Endocrine System Diseases, Hormones, Pituitary Diseases

Intervention / Treatment
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* Drug: Once weekly subcutaneous injection of TransCon hGH
* Drug: Once daily subcutaneous injection of Genotropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prepubertal children with GHD (either isolated or as part of a multiple pituitary hormone deficiency) in Tanner stage 1 (Tanner 1982) aged: Boys: 3-12 years, inclusive Girls: 3-11 years, inclusive Impaired height (HT) defined as at least 2.0 standard deviations (SD) below the mean height for chronological age and sex (HT SDS ≤ -2.0) according to the 2000 CDC Growth Charts for the United States Methods and Development, available at http://www.cdc.gov/growthcharts/ Diagnosis of GHD confirmed by 2 different GH stimulation tests, defined as a peak GH level of ≤10 ng/mL, determined with a validated assay Bone age (BA) at least 6 months less than chronological age Baseline IGF-1 level of at least 1 SD below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤-1) Written, signed informed consent of the parent(s) or legal guardian(s) of the subject and written assent of the subject (if the subject is able to read, understand, and sign) Exclusion Criteria: Children with a body weight below 12 kg Prior exposure to recombinant hGH or IGF-1 therapy Children with past or present intracranial tumor growth as confirmed by a sellar MRI scan (with contrast) at Screening (MRI results from up to 6 months prior to Screening may be accepted) Children with psychosocial dwarfism Children with idiopathic short stature History or presence of malignant disease; any evidence of present tumor growth Closed epiphyses Major medical conditions and/or presence of contraindication to hGH treatment Participation in any other trial of an investigational agent within 3 months prior to Screening

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TransCon hGH<br>Once weekly subcutaneous injection of TransCon hGH | Drug: Once weekly subcutaneous injection of TransCon hGH<br>* Once weekly subcutaneous injection<br>|
| Active Comparator: human growth hormone (Genotropin)<br>Once daily subcutaneous injection of Genotropin | Drug: Once daily subcutaneous injection of Genotropin<br>* Once daily subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Annualized height velocity (AHV) at 52 weeks for weekly lonapegsomatropin (TransCon hGH) and daily hGH treatment groups | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | Number of participants with Treatment-Emergent Adverse Events for the weekly lonapegsomatropin and daily hGH treatment groups | 52 Weeks | 
| Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Annualized height velocity (AHV) over 52 weeks for weekly lonapegsomatropin and daily hGH treatment groups. AHV by visit was determined by ANCOVA model with multiple imputation. For each imputed data set, an ANCOVA model with by visit AHV as the dependent variable, treatment and gender as factors, baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline height SDS - average parental height SDS as covariates were fitted. | Week 5, Week 13, Week 26, Week 39 and Week 52 | 
| Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height Standard Deviation Score (SDS) indicates a better outcome. The change from baseline in height SDS by visit was determined by ANCOVA model and included baseline age, peak GH levels (log transformed) at stimulation test and baseline height SDS as covariates, as well as treatment and gender as factors. | Week 5, Week 13, Week 26, Week 39 and Week 52 | 
| Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean. Average IGF-1 SDS by visit was determined by ANCOVA. The ANCOVA model included baseline age, peak GH levels (log transformed) at stimulation test, baseline IGF-1 SDS as covariates, as well as treatment and gender as factors. Modeled values begin at Week 13 corresponding with achievement of IGF-1 steady state. Average IGF-1 SDS values by visit for the Lonapegsomatropin group were derived from a population pharmacodynamic model; the average IGF-1 SDS values for the Genotropin group are represented by observed values. | Week 13, Week 26, Week 39, and Week 52 | 
| Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation | Number of participants with treatment emergent anti-hGH binding antibody formation during the 52 week study. All samples were negative for anti-hGH neutralizing antibodies. | Start of study treatment through Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sustained Release Growth Hormone, Growth Hormone Deficiency, Human Growth Hormone, hGH, GHD, rHGH, Pediatric Growth Hormone Deficiency, Long Acting Growth Hormone, Somatropin, Prodrug, Growth Failure, Growth Hormone Replacement Therapy, Sustained Release