Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Short Stature Associated With IGF-1 Deficiency

Study Overview
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Brief Summary
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This study is intended to assess the effects of once daily dosing of recombinant human insulin-like growth factor (rhIGF-1) in increasing height velocity.

Detailed Description
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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 growth hormone (GH) action. In this protocol, primary IGFD is defined as short stature (<-2 standard deviations [SDs] below the mean for age and gender), and abnormal serum IGF-1 (<-2 SDs below the mean for age and gender). The trial is an open-label, concentration-controlled trial conducted at up to 20 centers throughout the United States.

Official Title
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Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Short Stature Associated With Primary IGF-1 Deficiency: A Multi-Center, Open Label, Concentration-Controlled Study

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

Intervention / Treatment
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* Drug: rhIGF-1 (mecasermin) for a period of 86 weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronological age ≥ 3 Chronological age or bone age ≤ 12 for boys and ≤ 11 for girls Prepubertal at Visit 1 Height SD score of < -2 IGF-1 SD score of < -2 Exclusion Criteria: Prior treatment with GH, IGF-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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhIGF-1 QD<br>Subjects received subcutaneous injection (SC) injections of rhIGF-1 once a day. | Drug: rhIGF-1 (mecasermin) for a period of 86 weeks<br>* Once a day rhIGF-1 injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity From Pretreatment (Week 0) to Week 34 | Height was 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. The subject was repositioned between each measurement. Height velocity during an interval of time is defined as the change in height during the time interval divided by the duration of the time interval. Missing Week 34 heights were imputed using the last height SD score carried forward. | Pretreatment to Week 34 | 
| Height Velocity From Week 34 to 86 | Height was 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. The subject was repositioned between each measurement. Height velocity during an interval of time is defined as the change in height during the time interval divided by the duration of the time interval. Missing Week 86 heights were imputed using the last height SD score carried forward. | Week 34 to 86 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Height SD Score From Pretreatment to Week 34 | Height was 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. The subject was repositioned between each measurement. The SD score is calculated as the subject 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. | Pretreatment and Week 34 | 
| Change in Height SD Score From Pretreatment to Week 86 | Height was 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. Subjects were repositioned between each measurement. 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. | Pretreatment and Week 86 | 
| Change in Bone Age From Pretreatment to Week 86 Minus Change in Chronological Age | Plain X-rays of the left hand and wrist were exposed for bone age appraisal. The films were sent to a central facility for standardized evaluation. | Pretreatment to Week 86 | 
| Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86 | Growth factor panels for measuring IGFBP-1, IGFBP-2 and IGFBP-3 were evaluated from screening and at each study visit up to Week 86. Inter-quartile range (Q1-Q3) is 10th to 90th percentile. | Pretreatment and Week 86 | 
| Percent Change in Serum Concentration of ALS From Pretreatment to Week 86 | Growth factor panels for measuring ALS were evaluated from screening and at each study visit up to Week 86. Inter-quartile range (Q1-Q3) is 10th to 90th percentile. | Pretreatment and Week 86 | 

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