Growth Disorders, Insulin-Like Growth Factor-1 Deficiency
Conditions
Keywords
Primary IGF-1 Deficiency
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.
Interventions
DRUGrhIGF-1 (mecasermin, Tercica, Inc.)
Twice Daily Injection
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Study Initiation Date: 14 March 2004. Study completion Date: 02 July 2008. 44 investigators screened subjects; 14 did not enroll any subjects. 137 subjects were enrolled. Consent for one randomized subject was withdrawn prior to any study measurements. This subject was excluded from all analyses.
Pre-assignment details
Subject screening consisted of three staged clinic visits over 6 weeks, including a medical history, complete physical examination, IGF-1 measurements, a Growth Hormone (GH) stimulation test, and an IGF-1 generation test.
Participants by arm
| Arm | Count |
|---|---|
| Untreated Observational Group | 25 |
| 40 μg/kg BID (Twice Daily Dosing) 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. | 16 |
| 80 μg/kg BID (Twice Daily Dosing) Injection of rhIGF-1 80 μg/kg BID | 44 |
| 120 μg/kg BID (Twice Daily Dosing) Injection of rhIGF-1 120 μg/kg BID | 51 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 4 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Untreated | 120 μg/kg BID (Twice Daily Dosing) | 80 μg/kg BID (Twice Daily Dosing) | 40 μg/kg BID (Twice Daily Dosing) |
|---|---|---|---|---|---|
| Age, Continuous | 7.5 years STANDARD_DEVIATION 2.5 | 7.0 years STANDARD_DEVIATION 2.4 | 7.6 years STANDARD_DEVIATION 2.7 | 7.7 years STANDARD_DEVIATION 2.4 | 7.6 years STANDARD_DEVIATION 2.4 |
| Height Standard Deviation (SD) Score | -2.8 SD STANDARD_DEVIATION 0.7 | -2.8 SD STANDARD_DEVIATION 0.7 | -2.9 SD STANDARD_DEVIATION 0.8 | -2.7 SD STANDARD_DEVIATION 0.5 | -2.6 SD STANDARD_DEVIATION 0.6 |
| IGF-1 Standard Deviation (SD) Score | -2.8 SD STANDARD_DEVIATION 0.8 | -2.6 SD STANDARD_DEVIATION 0.7 | -3.0 SD STANDARD_DEVIATION 0.8 | -2.6 SD STANDARD_DEVIATION 0.7 | -2.8 SD STANDARD_DEVIATION 0.8 |
| Maximum Stimulated Growth Hormone | 18.6 ng/mL STANDARD_DEVIATION 12.1 | 17.0 ng/mL STANDARD_DEVIATION 6.5 | 20.7 ng/mL STANDARD_DEVIATION 16.8 | 17.8 ng/mL STANDARD_DEVIATION 9 | 16.9 ng/mL STANDARD_DEVIATION 6.2 |
| Race/Ethnicity, Customized Asian | 4 participants | 1 participants | 2 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black | 2 participants | 0 participants | 2 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic | 10 participants | 2 participants | 4 participants | 4 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 2 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 117 participants | 22 participants | 41 participants | 38 participants | 16 participants |
| Sex: Female, Male Female | 36 Participants | 10 Participants | 8 Participants | 14 Participants | 4 Participants |
| Sex: Female, Male Male | 100 Participants | 15 Participants | 43 Participants | 30 Participants | 12 Participants |
| Stratum Height Standard Deviation Score < -2.6 | 76 participants | 13 participants | 30 participants | 25 participants | 8 participants |
| Stratum Height Standard Deviation Score >= -2.6 | 60 participants | 12 participants | 21 participants | 19 participants | 8 participants |
| Weight | 18.6 Kg STANDARD_DEVIATION 5.3 | 17.8 Kg STANDARD_DEVIATION 4.6 | 18.5 Kg STANDARD_DEVIATION 5.7 | 19.4 Kg STANDARD_DEVIATION 5.4 | 18.5 Kg STANDARD_DEVIATION 4.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 25 | 16 / 16 | 37 / 44 | 43 / 51 |
| serious Total, serious adverse events | 1 / 25 | 1 / 16 | 2 / 44 | 5 / 51 |
Outcome results
Primary
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.
Time frame: Measured at baseline and at one year
Population: A modified intention-to-treat population consisting of all randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Height Velocity During the First Year - Intent to Treat (ITT)Population | 5.2 cm/yr | Standard Deviation 1 |
| 80 μg/kg BID (Twice Daily Dosing) | Height Velocity During the First Year - Intent to Treat (ITT)Population | 6.9 cm/yr | Standard Deviation 1 |
| 120 μg/kg BID (Twice Daily Dosing) | Height Velocity During the First Year - Intent to Treat (ITT)Population | 7.7 cm/yr | Standard Deviation 1.5 |
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [1.19, 2.39]ANCOVA
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [1.99, 3.16]ANCOVA
Comparison: The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: 0.003295% CI: [0.27, 1.31]ANCOVA
Secondary
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.
Time frame: Measured at baseline and at one year
Population: A modified intention-to-treat population that consists of all randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Change From Baseline in Height Standard Deviation (SD) Score at One Year - ITT Population | 0.02 SD/year | Standard Deviation 0.24 |
| 80 μg/kg BID (Twice Daily Dosing) | Change From Baseline in Height Standard Deviation (SD) Score at One Year - ITT Population | 0.38 SD/year | Standard Deviation 0.17 |
| 120 μg/kg BID (Twice Daily Dosing) | Change From Baseline in Height Standard Deviation (SD) Score at One Year - ITT Population | 0.48 SD/year | Standard Deviation 0.32 |
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [0.24, 0.5]ANCOVA
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [0.34, 0.6]ANCOVA
Comparison: The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: 0.049595% CI: [0, 0.22]ANCOVA
Secondary
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.
Time frame: Measured at baseline and at one year
Population: All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Changes in Bone Age From Baseline to One Year | 0.8 Year | Standard Deviation 0.3 |
| 80 μg/kg BID (Twice Daily Dosing) | Changes in Bone Age From Baseline to One Year | 1.1 Year | Standard Deviation 0.4 |
| 120 μg/kg BID (Twice Daily Dosing) | Changes in Bone Age From Baseline to One Year | 1.2 Year | Standard Deviation 0.5 |
Secondary
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.
Time frame: Study Day 1 and Day 7
Population: All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with measurements both pre and post exposure to rhGH. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | IGF Generation Test: Change of Serum IGF-1 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 40 ng/mL | Standard Deviation 49 |
| 80 μg/kg BID (Twice Daily Dosing) | IGF Generation Test: Change of Serum IGF-1 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 53 ng/mL | Standard Deviation 49 |
| 120 μg/kg BID (Twice Daily Dosing) | IGF Generation Test: Change of Serum IGF-1 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 48 ng/mL | Standard Deviation 43 |
Secondary
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.
Time frame: Study Day 1 and Day 7
Population: All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with measurements both pre and post exposure to rhGH. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | IGF Generation Test: Change of Serum IGFBP-3 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 744 mg/dL | Standard Deviation 459 |
| 80 μg/kg BID (Twice Daily Dosing) | IGF Generation Test: Change of Serum IGFBP-3 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 800 mg/dL | Standard Deviation 1095 |
| 120 μg/kg BID (Twice Daily Dosing) | IGF Generation Test: Change of Serum IGFBP-3 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) | 681 mg/dL | Standard Deviation 568 |
Secondary
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.
Time frame: Measured at baseline and at one year
Population: All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Percent Changes From Baseline in Serum Concentrations of IGF-1 at One Year | 64 Percent change | Standard Deviation 120 |
| 80 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of IGF-1 at One Year | 227 Percent change | Standard Deviation 220 |
| 120 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of IGF-1 at One Year | 266 Percent change | Standard Deviation 215 |
Secondary
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.
Time frame: Measured at baseline and at one year
Population: All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Percent Changes From Baseline in Serum Concentrations of IGF-2 at One Year | 14 Percent change | Standard Deviation 28 |
| 80 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of IGF-2 at One Year | -38 Percent change | Standard Deviation 37 |
| 120 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of IGF-2 at One Year | -37 Percent change | Standard Deviation 32 |
Secondary
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.
Time frame: Measured at baseline and at one year
Population: All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) at One Year | -16 Percent change | Standard Deviation 26 |
| 80 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) at One Year | 58 Percent change | Standard Deviation 84 |
| 120 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) at One Year | 61 Percent change | Standard Deviation 79 |
Secondary
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.
Time frame: Measured at baseline and at one year
Population: All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) at One Year | 13 Percent change | Standard Deviation 33 |
| 80 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) at One Year | -19 Percent change | Standard Deviation 22 |
| 120 μg/kg BID (Twice Daily Dosing) | Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) at One Year | -19 Percent change | Standard Deviation 28 |
Post Hoc
Change From Baseline in Height Standard Deviation (SD) Score at One Year - Completers
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.
Time frame: One Year
Population: All randomized subjects who completed 12 months of treatment in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Change From Baseline in Height Standard Deviation (SD) Score at One Year - Completers | 0.02 SD/year | Standard Deviation 0.24 |
| 80 μg/kg BID (Twice Daily Dosing) | Change From Baseline in Height Standard Deviation (SD) Score at One Year - Completers | 0.39 SD/year | Standard Deviation 0.17 |
| 120 μg/kg BID (Twice Daily Dosing) | Change From Baseline in Height Standard Deviation (SD) Score at One Year - Completers | 0.53 SD/year | Standard Deviation 0.3 |
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [0.25, 0.5]ANCOVA
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [0.39, 0.64]ANCOVA
Comparison: The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: 0.007195% CI: [0.04, 0.26]ANCOVA
Post Hoc
Height Velocity During the First Year for Subjects - Completers
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.
Time frame: One Year
Population: All randomized subjects who completed 12 months of treatment in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Untreated | Height Velocity During the First Year for Subjects - Completers | 5.2 cm/year | Standard Deviation 1 |
| 80 μg/kg BID (Twice Daily Dosing) | Height Velocity During the First Year for Subjects - Completers | 7.0 cm/year | Standard Deviation 1 |
| 120 μg/kg BID (Twice Daily Dosing) | Height Velocity During the First Year for Subjects - Completers | 7.9 cm/year | Standard Deviation 1.4 |
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [1.26, 2.4]ANCOVA
Comparison: The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: <0.000195% CI: [2.26, 3.39]ANCOVA
Comparison: The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.p-value: 0.000295% CI: [0.5, 1.51]ANCOVA