Growth Disorders, Insulin-Like Growth Factor-1 Deficiency
Conditions
Keywords
Primary IGF-1 Deficiency, IGF-1
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.
Interventions
DRUGrhIGF-1 (mecasermin) for a period of 86 weeks
Once a day rhIGF-1 injections
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
This was a open-label, multi-center and single-arm study conducted at 12 investigational sites (11 active) between 12 January 2005 and 14 January 2009. A total of 45 subjects were enrolled in this study.
Pre-assignment details
The screening period consisted of two-staged clinic visits for up to 6 weeks, followed by an open-label treatment period of 86 weeks.
Participants by arm
| Arm | Count |
|---|---|
| rhIGF-1 QD During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Non-compliance | 2 |
| Overall Study | Other | 1 |
| Overall Study | Subject/Parent Decision | 7 |
Baseline characteristics
| Characteristic | rhIGF-1 QD |
|---|---|
| Age, Continuous | 8.7 years STANDARD_DEVIATION 2.8 |
| Age, Customized Adolescents (12-17 years) | 9 Participants |
| Age, Customized Children (2-11 years) | 36 Participants |
| Body Mass Index Standard Deviation (SD) Score | -0.4 SDs STANDARD_DEVIATION 0.7 |
| Bone Age Imputed | 7.2 years STANDARD_DEVIATION 2.6 |
| Height for Age SD Score | -2.7 SDs STANDARD_DEVIATION 0.6 |
| IGF-1 SD Score | -2.6 SDs STANDARD_DEVIATION 0.5 |
| IGFBP-3 SD Score | -0.7 SDs STANDARD_DEVIATION 1 |
| Maximum Stimulated GH | 20.5 nanogram per milliliter STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized Black | 1 participants |
| Race/Ethnicity, Customized Hispanic | 12 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 31 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 38 Participants |
| Weight for Age SD Score | -2.3 SDs STANDARD_DEVIATION 0.7 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 45 |
| other Total, other adverse events | 41 / 45 |
| serious Total, serious adverse events | 2 / 45 |
Outcome results
Primary
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.
Time frame: Pretreatment to Week 34
Population: The ITT population included all treated subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1 QD | Height Velocity From Pretreatment (Week 0) to Week 34 | 7.0 centimeters per year (cm/yr) | Standard Deviation 1.5 |
Primary
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.
Time frame: Week 34 to 86
Population: The ITT population included all treated subjects. Only subjects in the ITT population who continued past Week 34 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1 QD | Height Velocity From Week 34 to 86 | 6.7 cm/yr | Standard Deviation 1.8 |
Secondary
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.
Time frame: Pretreatment to Week 86
Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1 QD | Change in Bone Age From Pretreatment to Week 86 Minus Change in Chronological Age | 0.2 years | Standard Deviation 0.68 |
Secondary
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.
Time frame: Pretreatment and Week 34
Population: The ITT population included all treated subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1 QD | Change in Height SD Score From Pretreatment to Week 34 | 0.21 SDs | Standard Deviation 0.2 |
Secondary
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.
Time frame: Pretreatment and Week 86
Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1 QD | Change in Height SD Score From Pretreatment to Week 86 | 0.45 SDs | Standard Deviation 0.39 |
Secondary
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.
Time frame: Pretreatment and Week 86
Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| rhIGF-1 QD | Percent Change in Serum Concentration of ALS From Pretreatment to Week 86 | -7.7 percent change |
Secondary
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.
Time frame: Pretreatment and Week 86
Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| rhIGF-1 QD | Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86 | IGFBP-1 | -89.6 percent change |
| rhIGF-1 QD | Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86 | IGFBP-2 | 37.9 percent change |
| rhIGF-1 QD | Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86 | IGFBP-3 | 0 percent change |
Post Hoc
Increase in Height Velocity 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. 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.
Time frame: Pretreatment to Week 34
Population: Completer population included all subjects who remained on study to Week 86. Subjects who completed Week 34 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1 QD | Increase in Height Velocity From Pretreatment to Week 34 | 1.3 cm/yr | Standard Deviation 3.56 |
Post Hoc
Increase in Height Velocity 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. 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.
Time frame: Pretreatment to Week 86
Population: Completer population included all subjects who remained on study to Week 86.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhIGF-1 QD | Increase in Height Velocity From Pretreatment to Week 86 | 1.3 cm/yr | Standard Deviation 3.58 |