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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: rhIGF-1 (mecasermin, Tercica, Inc.)


Participation Criteria
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Eligibility Criteria
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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.

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 |
| --- | --- |
| No Intervention: Untreated<br>Observational Group | |
| Experimental: 40 μg/kg BID (twice daily dosing)<br>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. | Drug: rhIGF-1 (mecasermin, Tercica, Inc.)<br>* Twice Daily Injection<br>|
| Experimental: 80 μg/kg BID (twice daily dosing)<br>Injection of rhIGF-1 80 μg/kg BID | Drug: rhIGF-1 (mecasermin, Tercica, Inc.)<br>* Twice Daily Injection<br>|
| Experimental: 120 μg/kg BID (twice daily dosing)<br>Injection of rhIGF-1 120 μg/kg BID | Drug: rhIGF-1 (mecasermin, Tercica, Inc.)<br>* Twice Daily Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity During the First Year - Intent to Treat (ITT)Population | 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. | Measured at baseline and at one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Height Standard Deviation (SD) Score at One Year - ITT Population | 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. | Measured at baseline and at one year | 
| Changes in Bone Age From Baseline to 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. | Measured at baseline and at one year | 
| Percent Changes From Baseline in Serum Concentrations of IGF-1 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. | Measured at baseline and at one year | 
| Percent Changes From Baseline in Serum Concentrations of IGF-2 at One Year | Blood sample was collected for measuring the level of IGF-2 in the growth factor panel. | Measured at baseline and at one year | 
| Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) 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. | Measured at baseline and at one year | 
| Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) 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. | Measured at baseline and at one year | 
| IGF Generation Test: Change of Serum IGF-1 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 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. | Study Day 1 and Day 7 | 
| IGF Generation Test: Change of Serum IGFBP-3 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 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. | Study Day 1 and Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary IGF-1 Deficiency