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

Phase 3

Completed

Conditions: Insulin-Like Growth Factor-1 Deficiency
Growth Disorders

Interventions: Drug: rhIGF-1 (mecasermin, Tercica, Inc.)

Registration Number: NCT00125164

Lead Sponsor: Ipsen

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 137

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
40 μg/kg BID (twice daily dosing)	rhIGF-1 (mecasermin, Tercica, Inc.)	Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
80 μg/kg BID (twice daily dosing)	rhIGF-1 (mecasermin, Tercica, Inc.)	Injection of rhIGF-1 80 μg/kg BID
120 μg/kg BID (twice daily dosing)	rhIGF-1 (mecasermin, Tercica, Inc.)	Injection of rhIGF-1 120 μg/kg BID

Primary Outcome Measures

Name	Time	Method
Height Velocity During the First Year - Intent to Treat (ITT)Population	Measured at baseline and at one year	Height to be measured standing without shoes as the average of three measurements by the same observer using identical technique with a Harpenden or other wall mounted stadiometer. Reposition subject between each measurement.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Height Standard Deviation (SD) Score at One Year - ITT Population	Measured at baseline and at one year	Height to be measured standing without shoes as the average of three measurements by the same observer using identical technique with a Harpenden or other wall mounted stadiometer. Reposition subject between each measurement. Please note that Standard Deviation (SD) Score is a term used in growth studies. The SD Score is calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child.
Changes in Bone Age From Baseline to One Year	Measured at baseline and at one year	Plain X-rays of the left hand and wrist exposed for bone age appraisal. The films are sent to a central facility for standardized evaluation.
Percent Changes From Baseline in Serum Concentrations of IGF-1 at One Year	Measured at baseline and at one year	Blood sample was collected while subject is in a fasting state for measuring the level of IGF-1 in the growth factor panel.
Percent Changes From Baseline in Serum Concentrations of IGF-2 at One Year	Measured at baseline and at one year	Blood sample was collected for measuring the level of IGF-2 in the growth factor panel.
Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) at One Year	Measured at baseline and at one year	Blood sample was collected for measuring the level of insulin-like growth factor binding protein-2 (IGFBP-2) in the growth factor panel.
Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) at One Year	Measured at baseline and at one year	Blood sample was collected while subject is in a fasting state for measuring the level of IGFBP-3 in the growth factor panel.
IGF Generation Test: Change of Serum IGF-1 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH)	Study Day 1 and Day 7	Blood drawn at Study Day 1, followed by 7 days of rhGH daily dosing at 0.05 mg/kg of body weight. Additional blood draw at Study Day 7.
IGF Generation Test: Change of Serum IGFBP-3 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH)	Study Day 1 and Day 7	Blood drawn at Study Day 1, followed by 7 days of rhGH daily dosing at 0.05 mg/kg of body weight. Additional blood draw at Study Day 7.