Prepubertal Children With Growth Failure Associated With Primary Insulin-Like Growth Factor-1 (IGF-1) Deficiency

Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Prepubertal Children With Growth Failure Associated With Primary IGF-1 Deficiency: A Phase 3, Randomized, Open Label, Observation-Controlled, Multicenter, Parallel-Dose Comparison Trial

This study is intended to determine whether twice daily weight based dosing with recombinant human insulin-like growth factor (rhIGF-1) will safely and effectively increase the growth of prepubertal children with short stature associated with low IGF-1 levels but who produce sufficient growth hormone (GH). Subjects will be randomized to either an observation arm or to active treatment.

Prepubertal growth failure associated with primary IGF-1 deficiency (IGFD). Primary IGFD is a term that has been used to describe patients with intrinsic cellular defects in GH action. In this protocol, primary IGFD is defined as short stature (height standard deviation score[SDS]<-2 below the mean for age and gender), low serum IGF-1 (IGF-1 SDS <-2 below the mean for age and gender), and levels of growth hormone (GH) that are normal (≥7ng/mL) after a GH stimulation test. Primary IGFD is believed to result from a lower than normal ability to produce IGF-1 when exposed to normal levels of GH, i.e., a type of GH insensitivity or GH resistance.

This trial is one year, randomized, open label, observation-controlled, parallel-dose comparison efficacy and safety study conducted in approximately 40 centers across the United States.

Inclusion Criteria:

• Chronological age ≥ 3 and chronological or bone age less than or equal to 11 years inclusive in girls;
• Chronological age ≥ 3 and chronological or bone age less than or equal to 12 years inclusive for boys
• Prepubertal
• Height SD score of < -2
• IGF-1 SD score of < -2

Exclusion Criteria:

• Prior treatment with rhGH, rhIGF-1, or other growth-influencing medications
• Growth failure associated with other identifiable causes (e.g., syndromes, chromosomal abnormality)
• Chronic illness such as diabetes, cystic fibrosis, etc.