Efficacy and Safety of a High Dosage Compared to the Label Dosage of Somatropin in Early Pubertal Stage Children With Growth Hormone Deficiency

Study Overview
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Brief Summary
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Multi-center, randomized, controlled, open-label, phase III study comparing the effects of two different dosages of somatropin treatment (in-label or doubled) after 12 and 24 months of treatment, on height velocity in early pubertal children with growth hormone deficiency (GHD). The study will be conducted in Italy. Approximately 26 subjects will participate in this study, distributed as 13 in the in-label dosage group (group A) and 13 in the doubled dosage group (group B).

Official Title
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Efficacy and Safety of a High Dosage Compared to the Label Dosage of Humatrope in Early Pubertal Stage Children With Growth Hormone Deficiency

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Somatropin
* Drug: Somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Height velocity (cm/y) less than 25th percentile at the time of diagnosis. diagnosis of GHD Replacement therapy at label dosage (from 0.025 to 0.035 mg/kg/day) must be started at least 1 year before the enrolment in this study, but at most 3 years before enrolment Bone age less than 12 years for girls and less than 14 years for boys. This assessment should be made by the central reader of bone ages, based on the x-ray taken at Visit 0. Informed consent obtained from either both of the subject's parents or legal representative. Exclusion Criteria: Pubertal clinical stage less than 2 and greater than 3 according to Tanner score (for male subjects a volume of testicle greater than 15 mL). Any evidence of active malignancy. In case of previous surgical removal of both diencephalic and hypophysial masses, an MRI, performed within six months before enrollment into the study, must exclude the growth of residual tumoral tissue. Any known chronic disease such as diabetes mellitus, hepatic disease (defined by elevated liver enzymes 3-fold the upper limit of normal ranges), renal disease with creatinine levels greater than 130 micromol/L, or congestive heart failure. Glucocorticoid therapy in supra physiological doses (inhaled corticoids will be accepted if below 3 puffs/day, for no more than 10 days consecutively). Current or previous therapy with any therapy that may directly influence growth, including growth hormone releasing hormone, estrogens and anabolic steroids.

Ages Eligible for Study
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Maximum Age: 14 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: 1<br>Doubled dosage | Drug: Somatropin<br>* Doubled dosage with respect to the pre-enrollment (in-label) dosage<br>* Other names: Humatrope;|
| Active Comparator: 2<br>In-label dosage | Drug: Somatropin<br>* In-label dosage<br>* Other names: Humatrope;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity Standard Deviation Score (SDS) at 12-Month Endpoint | Height velocity (difference between 2 height measurements, divided by years elapsed between measurements) SDS was derived by subtracting age and gender-matched population mean height velocity from patient's height velocity (based on measurements 12 months apart) then dividing this value by age and gender-matched population height velocity SD. | 12-Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12-Month and 24-Month Endpoints in Height Standard Deviation Score (SDS) | This was derived by subtracting the age-and-gender-matched population 50th percentile height from the patient's height and then dividing this value by the age-and-gender-matched population height SD. | Baseline, 12-Months, 24-Months | 
| Height Velocity Standard Deviation Score (SDS) at 24 Month Endpoint | Height velocity (difference between 2 height measurements, divided by years elapsed between measurements) SDS was derived by subtracting age and gender-matched population mean height velocity from patient's height velocity (based on measurements 12 months apart) then dividing this value by age and gender-matched population height velocity SD. | 24 Months |