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

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

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).

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.