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

Phase 2

Completed

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

Interventions: Drug: rhIGF-1 (mecasermin) for a period of 86 weeks

Registration Number: NCT00125190

Lead Sponsor: Ipsen

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
rhIGF-1 QD	rhIGF-1 (mecasermin) for a period of 86 weeks	Subjects received subcutaneous injection (SC) injections of rhIGF-1 once a day.

Primary Outcome Measures

Name	Time	Method
Height Velocity From Pretreatment (Week 0) to Week 34	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. 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.
Height Velocity From Week 34 to 86	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.

Secondary Outcome Measures

Name	Time	Method
Change in Height SD Score From Pretreatment to Week 34	Pretreatment and 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.
Change in Height SD Score From Pretreatment to Week 86	Pretreatment and 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.
Change in Bone Age From Pretreatment to Week 86 Minus Change in Chronological Age	Pretreatment to Week 86	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.
Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86	Pretreatment and 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.
Percent Change in Serum Concentration of ALS From Pretreatment to Week 86	Pretreatment and 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.