Fetal Growth Retardation
Conditions
Brief summary
To estimate the percentage of children with serum IGF-1 \> 2 standard deviation (compared to a child of the same gender and age and without growth hormone (GH) deficiency) 9 months and 12 months after initiation of GH treatment.
Interventions
DRUGGenotonorm (Somatropin)
0.40 mg/kg/week dived in 7 daily subcutaneous injections during 2 years
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 9 Years
Healthy volunteers
No
Inclusion criteria
* Chronological age between 4 and 9 years for a boy and 4 and 7 years for a girl. * Measured Height \< -2.5 Standard Deviation
Exclusion criteria
* Pubertal signs ie: testis volume \> or = 4 ml in boys and breast stage \> or = B2 (Tanner) * Serious chronic disease (diabetes, renal insufficiency, heart failure, hepatic insufficiency, neoplasia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Children With Insulin Growth Factor-1 (IGF-1) > 2 Standard Deviation (SD) at 9 and 12 Months | 9 and 12 months | Percentage of children with serum IGF-1 \> 2 SD (compared to a child of the same gender and age and without growth hormone (GH) deficiency) 9 months and 12 months after initiation of GH treatment. 9 months and 12 months are combined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Height SD BA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | Baseline, 12 and 24 months | The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 12 or 24 months minus height in SD at Baseline. |
| Analysis of Covariance (ANCOVA) for Height SD CA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | Baseline, 12 months | Change in Height SD (CA) was calculated as: Height SD (CA) at 12 months minus Height SD (CA) at Baseline |
| ANCOVA for Height SD CA at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | Baseline, 24 months | Height SD (CA) at 24 months. |
| ANCOVA for Height SD BA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | Baseline, 12 months | Change in Height SD (BA) was calculated as: Height SD (BA) at 12 months minus Height SD (BA) at Baseline |
| ANCOVA for Height SD BA at 24 Months in Children With IGF-1 <= 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | Baseline, 24 months | Height SD (BA) at 24 months |
| Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 6, 9, 12, 15, 18, 21, and 24 months | IGF-1 SD was calculated at each study time point using gender specific IGF-1 reference mean and SD for the CA of the child on the date of the corresponding IGF-1 blood sample: IGF-1 SD = (IGF-1 minus reference mean) divided by reference SD |
| Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 6, 9, 12, 15, 18, 21, and 24 months | IGF-1 SD was calculated at each study time point using these gender specific IGF-1 reference means and SDs for the CA of the child on the date of the corresponding IGF-1 blood sample: IGF-1 SD = (IGF-1 - reference mean) / reference SD |
| IGF-1/Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) Ratio at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 12 and 24 months | — |
| Change in Height SD Chronological Age (CA) From Baseline at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | Baseline, 12 months | The height in SD was calculated using Sempe reference means and standard deviations for height. Change in height SD was calculated as height in SD at 12 months minus height in SD at Baseline. |
| Change in Height SD CA From Baseline at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | Baseline, 24 months | The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 24 months minus height in SD at Baseline. |
| Change in Height SD CA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | Baseline, 12 and 24 months | The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 12 or 24 months minus height in SD at Baseline. |
| Change in Height SD Bone Age (BA) From Baseline at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | Baseline, 12 months | The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 12 months minus height in SD at Baseline. |
| Change in Height SD BA From Baseline at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | Baseline, 24 months | The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 24 months minus height in SD at Baseline. |
| IGF-1/IGFBP-3 Ratio at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 and 24 months | — |
| Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 12 and 24 months | Growth rate SD CA at 12 months was calculated as:(Growth rate at 12 months minus reference mean for CA at 12 months) divided by reference SD for CA at 12 months Growth rate SD CA at 24 months was calculated as:(Growth rate at 24 months minus reference mean for CA at 24 months) divided by reference SD for CA at 24 months |
| Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 and 24 months | Growth rate SD CA at 12 months was calculated as: (Growth rate at 12 months minus reference mean for CA at 12 months) divided by reference SD for CA at 12 months Growth rate SD CA at 24 months was calculated as: (Growth rate at 24 months minus reference mean for CA at 24 months) divided by reference SD for CA at 24 months |
| Summary of Growth Rate SD (BA) at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | Baseline, 12 months | Growth rate SD BA at 12 months was calculated as: (Growth rate at 12 months minus reference mean for BA at 12 months) divided by reference SD for BA at 12 months |
| Summary of Growth Rate SD (BA) at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | Baseline, 24 months | Growth rate SD BA at 24 months was calculated as: (Growth rate at 24 months minus reference mean for BA at 24 months) divided by reference SD for BA at 24 months |
| Summary of Growth Rate SD (BA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 and 24 months | Growth rate SD BA at 12 months was calculated as: (Growth rate at 12 months minus reference mean for BA at 12 months) divided by reference SD for CA at 12 months Growth rate SD BA at 24 months was calculated as: (Growth rate at 24 months minus reference mean for BA at 24 months) divided by reference SD for CA at 24 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Growth Rate at 12 and 24 Months | 12 and 24 months | Growth Rate was calculated at 12 months as: (Height at 12 months minus Height at Day 0) divided by {(Date of 12 months minus Date of Day 0) divided by 365.25} Growth Rate was calculated at 24 months as: (Height at 24 months minus Height at 12 months) divided by {(Date of 24 months minus Date of 12 months) divided by 365.25} |
| Summary of Body Mass Index (BMI) at 12 and 24 Months | 12 and 24 months | BMI was calculated at 12 months and 24 months as: (Weight at 12 or 24 months divided by Height at 12 or 24 months) squared |
| Change in BA From Baseline at 12 and 24 Months | Baseline, 12 and 24 months | Change in BA was calculated as: (12 or 24 months minus Screening) |
| BA/CA at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 12 and 24 months | The BA/CA ratio was calculated at Screening, 12 and 24 months. The CA was the age on the date that the corresponding BA X-ray was performed. |
| BA/CA at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 and 24 months | The BA/CA ratio was calculated at Screening, 12 and 24 months. The CA was the age on the date that the corresponding BA X-ray was performed. |
| Change in Height From Baseline | Baseline, 12 and 24 months | The standing height measurements were performed at the same time of the day by using a wallmounted device (e.g. Harpenden Stadiometer) at each study visit. The pre-specified clinical outcomes were analyzed at 12 and 24 months. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Genotonorm Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Genotonorm |
|---|---|
| Age, Customized >=12 years | 0 participants |
| Age, Customized <4 years | 1 participants |
| Age, Customized Between 4 and 8 years | 49 participants |
| Age, Customized Between 8 and 12 years | 7 participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 57 |
| serious Total, serious adverse events | 6 / 57 |
Outcome results
Primary
Percentage of Children With Insulin Growth Factor-1 (IGF-1) > 2 Standard Deviation (SD) at 9 and 12 Months
Percentage of children with serum IGF-1 \> 2 SD (compared to a child of the same gender and age and without growth hormone (GH) deficiency) 9 months and 12 months after initiation of GH treatment. 9 months and 12 months are combined.
Time frame: 9 and 12 months
Population: The safety analysis set (SAS) was defined as all patients who received at least one dose of GH treatment. Number of Participants Analyzed = Number of children treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotonorm | Percentage of Children With Insulin Growth Factor-1 (IGF-1) > 2 Standard Deviation (SD) at 9 and 12 Months | No | 86.0 percentage of participants |
| Genotonorm | Percentage of Children With Insulin Growth Factor-1 (IGF-1) > 2 Standard Deviation (SD) at 9 and 12 Months | Yes | 14.0 percentage of participants |
Comparison: Applies to no.95% CI: [74.2, 93.7]
Comparison: Applies to yes.95% CI: [6.3, 25.8]
Secondary
Analysis of Covariance (ANCOVA) for Height SD CA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months
Change in Height SD (CA) was calculated as: Height SD (CA) at 12 months minus Height SD (CA) at Baseline
Time frame: Baseline, 12 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months or with IGF-1 \> 2 SD at 9 and 12 months and with evaluable height SD CA data at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | Analysis of Covariance (ANCOVA) for Height SD CA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | -1.94 SD for CA | Standard Error 0.04 |
| Genotonorm (IGF-1 > 2 SD at 9 and 12 Months) | Analysis of Covariance (ANCOVA) for Height SD CA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | -1.59 SD for CA | Standard Error 0.1 |
p-value: 0.002ANCOVA
Secondary
ANCOVA for Height SD BA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months
Change in Height SD (BA) was calculated as: Height SD (BA) at 12 months minus Height SD (BA) at Baseline
Time frame: Baseline, 12 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months or with IGF-1 \> 2 SD at 9 and 12 months and with evaluable height SD BA data at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | ANCOVA for Height SD BA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | 0.56 SD for BA | Standard Error 0.22 |
| Genotonorm (IGF-1 > 2 SD at 9 and 12 Months) | ANCOVA for Height SD BA at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | 0.76 SD for BA | Standard Error 0.48 |
p-value: 0.708ANCOVA
Secondary
ANCOVA for Height SD BA at 24 Months in Children With IGF-1 <= 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months
Height SD (BA) at 24 months
Time frame: Baseline, 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months or with IGF-1 \> 2 SD at 9 and 12 months and with evaluable height SD BA data at 24 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | ANCOVA for Height SD BA at 24 Months in Children With IGF-1 <= 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | 0.05 SD for BA | Standard Error 0.25 |
| Genotonorm (IGF-1 > 2 SD at 9 and 12 Months) | ANCOVA for Height SD BA at 24 Months in Children With IGF-1 <= 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | 0.64 SD for BA | Standard Error 0.53 |
p-value: 0.325ANCOVA
Secondary
ANCOVA for Height SD CA at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months
Height SD (CA) at 24 months.
Time frame: Baseline, 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months or with IGF-1 \> 2 SD at 9 and 12 months and with evaluable height SD CA data at 24 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | ANCOVA for Height SD CA at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | -1.53 SD for CA | Standard Error 0.06 |
| Genotonorm (IGF-1 > 2 SD at 9 and 12 Months) | ANCOVA for Height SD CA at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months and IGF-1 > 2 SD at 9 and 12 Months | -1.18 SD for CA | Standard Error 0.14 |
p-value: 0.023ANCOVA
Secondary
Change in Height SD BA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months
The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 12 or 24 months minus height in SD at Baseline.
Time frame: Baseline, 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \> 2 SD at 9 or 12 months with evaluable height SD BA data at 12 and 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change in Height SD BA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 24 Months | 0.64 SD for BA | Standard Deviation 1.3 |
| Genotonorm | Change in Height SD BA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 Months | 0.64 SD for BA | Standard Deviation 1.19 |
Secondary
Change in Height SD BA From Baseline at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 24 months minus height in SD at Baseline.
Time frame: Baseline, 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable height SD BA data at 24 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | Change in Height SD BA From Baseline at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 0.12 Height in SD | Standard Deviation 1.86 |
Secondary
Change in Height SD Bone Age (BA) From Baseline at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 12 months minus height in SD at Baseline.
Time frame: Baseline, 12 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable height SD BA data at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | Change in Height SD Bone Age (BA) From Baseline at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 0.44 SD for BA | Standard Deviation 1.34 |
Secondary
Change in Height SD CA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months
The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 12 or 24 months minus height in SD at Baseline.
Time frame: Baseline, 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \> 2 SD at 9 and 12 months with evaluable Height SD CA data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change in Height SD CA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 Months | 1.13 SD for BA | Standard Deviation 0.35 |
| Genotonorm | Change in Height SD CA From Baseline at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 24 Months | 1.53 SD for BA | Standard Deviation 0.2 |
Secondary
Change in Height SD CA From Baseline at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
The height in SD was calculated using Sempe reference means and SDs for height. Change in height SD was calculated as height in SD at 24 months minus height in SD at Baseline.
Time frame: Baseline, 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable height SD CA data at 24 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | Change in Height SD CA From Baseline at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 1.24 SD for CA | Standard Deviation 0.48 |
Secondary
Change in Height SD Chronological Age (CA) From Baseline at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
The height in SD was calculated using Sempe reference means and standard deviations for height. Change in height SD was calculated as height in SD at 12 months minus height in SD at Baseline.
Time frame: Baseline, 12 months
Population: The full analysis set (FAS) included all patients who received at least one dose of assigned treatment and had at least one subsequent rating of IGF-1. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable height SD CA data at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | Change in Height SD Chronological Age (CA) From Baseline at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 0.81 SD for CA | Standard Deviation 0.26 |
Secondary
IGF-1/IGFBP-3 Ratio at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months
Time frame: 12 and 24 months
Population: SAS. Number of Participants Analyzed = Number of children with IGF-1 \> 2 SD at 9 and 12 months with evaluable IGF-1/IGFBP-3 data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | IGF-1/IGFBP-3 Ratio at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 Months | 0.23 ratio | Standard Deviation 0.03 |
| Genotonorm | IGF-1/IGFBP-3 Ratio at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 24 Months | 0.21 ratio | Standard Deviation 0.06 |
Secondary
IGF-1/Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) Ratio at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
Time frame: 12 and 24 months
Population: SAS. Number of Participants Analyzed = Number of children treated. n = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable IGF-1/IGFBP-3 data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | IGF-1/Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) Ratio at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 12 Months (n=44) | 0.17 ratio | Standard Deviation 0.06 |
| Genotonorm | IGF-1/Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) Ratio at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 24 Months (n=45) | 0.19 ratio | Standard Deviation 0.07 |
Secondary
Summary of Growth Rate SD (BA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months
Growth rate SD BA at 12 months was calculated as: (Growth rate at 12 months minus reference mean for BA at 12 months) divided by reference SD for CA at 12 months Growth rate SD BA at 24 months was calculated as: (Growth rate at 24 months minus reference mean for BA at 24 months) divided by reference SD for CA at 24 months
Time frame: 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \> 2 SD at 9 and 12 months with evaluable growth rate SD BA data at 12 months. n = Number of children with IGF-1 \> 2 SD at 9 and 12 months with evaluable growth rate SD BA data at 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Summary of Growth Rate SD (BA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 Months | 4.02 SD for BA | Standard Deviation 2.37 |
| Genotonorm | Summary of Growth Rate SD (BA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 24 Months (n=6) | 1.71 SD for BA | Standard Deviation 2.26 |
Secondary
Summary of Growth Rate SD (BA) at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
Growth rate SD BA at 12 months was calculated as: (Growth rate at 12 months minus reference mean for BA at 12 months) divided by reference SD for BA at 12 months
Time frame: Baseline, 12 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable growth rate SD BA data at 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | Summary of Growth Rate SD (BA) at 12 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 2.38 SD for CA | Standard Deviation 1.88 |
Secondary
Summary of Growth Rate SD (BA) at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
Growth rate SD BA at 24 months was calculated as: (Growth rate at 24 months minus reference mean for BA at 24 months) divided by reference SD for BA at 24 months
Time frame: Baseline, 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable growth rate SD BA data at 24 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genotonorm | Summary of Growth Rate SD (BA) at 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 1.26 SD for BA | Standard Deviation 1.62 |
Secondary
Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months
Growth rate SD CA at 12 months was calculated as: (Growth rate at 12 months minus reference mean for CA at 12 months) divided by reference SD for CA at 12 months Growth rate SD CA at 24 months was calculated as: (Growth rate at 24 months minus reference mean for CA at 24 months) divided by reference SD for CA at 24 months
Time frame: 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \> 2 SD at 9 and 12 months with evaluable growth rate SD CA data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 Months | 5.24 SD for CA | Standard Deviation 1.64 |
| Genotonorm | Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 24 Months | 2.15 SD for CA | Standard Deviation 2.21 |
Secondary
Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
Growth rate SD CA at 12 months was calculated as:(Growth rate at 12 months minus reference mean for CA at 12 months) divided by reference SD for CA at 12 months Growth rate SD CA at 24 months was calculated as:(Growth rate at 24 months minus reference mean for CA at 24 months) divided by reference SD for CA at 24 months
Time frame: 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable growth rate SD CA data at 12 months. n = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable growth rate SD CA data at 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 12 Months | 3.77 SD for CA | Standard Deviation 1.68 |
| Genotonorm | Summary of Growth Rate SD (CA) at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 24 Months (n=47) | 1.74 SD for CA | Standard Deviation 1.51 |
Secondary
Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months
IGF-1 SD was calculated at each study time point using these gender specific IGF-1 reference means and SDs for the CA of the child on the date of the corresponding IGF-1 blood sample: IGF-1 SD = (IGF-1 - reference mean) / reference SD
Time frame: 6, 9, 12, 15, 18, 21, and 24 months
Population: SAS. Number of Participants Analyzed = Number of children treated. n = Number of children with IGF-1 \> 2 SD at 9 and 12 months with evaluable IGF-1 SD data at 6, 9, 12, 15, 18, 21, and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 6 Months (n=7) | 2.32 SD | Standard Deviation 0.68 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 9 Months (n=6) | 2.35 SD | Standard Deviation 0.19 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 Months (n=8) | 2.50 SD | Standard Deviation 0.27 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 15 Months (n=7) | 1.40 SD | Standard Deviation 1.08 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 18 Months (n=7) | 2.12 SD | Standard Deviation 1.18 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 21 Months (n=7) | 1.82 SD | Standard Deviation 1.09 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 24 Months (n=8) | 1.81 SD | Standard Deviation 1.03 |
Secondary
Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
IGF-1 SD was calculated at each study time point using gender specific IGF-1 reference mean and SD for the CA of the child on the date of the corresponding IGF-1 blood sample: IGF-1 SD = (IGF-1 minus reference mean) divided by reference SD
Time frame: 6, 9, 12, 15, 18, 21, and 24 months
Population: SAS. Number of Participants Analyzed = Number of children treated. n = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable IGF-1 SD data at 6, 9, 12, 15, 18, 21, and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 6 Months (n=49) | 0.65 SD | Standard Deviation 1.11 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 9 Months (n=46) | 0.93 SD | Standard Deviation 1.26 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 12 Months (n=44) | 1.04 SD | Standard Deviation 0.96 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 15 Months (n=40) | 0.88 SD | Standard Deviation 1.28 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 18 Months (n=43) | 0.88 SD | Standard Deviation 1.17 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 21 Months (n=41) | 0.82 SD | Standard Deviation 0.93 |
| Genotonorm | Summary of IGF-1 SD at 6, 9, 12, 15, 18, 21, and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 24 Months (n=45) | 0.85 SD | Standard Deviation 1.17 |
Other Pre-specified
BA/CA at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months
The BA/CA ratio was calculated at Screening, 12 and 24 months. The CA was the age on the date that the corresponding BA X-ray was performed.
Time frame: 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \> 2 SD at 9 and 12 months with evaluable BA/CA data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | BA/CA at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 12 Months | 0.80 ratio | Standard Deviation 0.21 |
| Genotonorm | BA/CA at 12 and 24 Months in Children With IGF-1 > 2 SD at 9 and 12 Months | 24 Months | 0.83 ratio | Standard Deviation 0.09 |
Other Pre-specified
BA/CA at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months
The BA/CA ratio was calculated at Screening, 12 and 24 months. The CA was the age on the date that the corresponding BA X-ray was performed.
Time frame: 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with IGF-1 \< = 2 SD at 9 or 12 months with evaluable BA/CA data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | BA/CA at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 12 Months | 0.74 ratio | Standard Deviation 0.17 |
| Genotonorm | BA/CA at 12 and 24 Months in Children With IGF-1 < = 2 SD at 9 or 12 Months | 24 Months | 0.82 ratio | Standard Deviation 0.16 |
Other Pre-specified
Change in BA From Baseline at 12 and 24 Months
Change in BA was calculated as: (12 or 24 months minus Screening)
Time frame: Baseline, 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children treated. n = Number of children with evaluable BA data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change in BA From Baseline at 12 and 24 Months | 12 Months (n=33) | 1.2 year | Standard Deviation 0.9 |
| Genotonorm | Change in BA From Baseline at 12 and 24 Months | 24 Months (n=31) | 2.5 year | Standard Deviation 1.1 |
Other Pre-specified
Change in Height From Baseline
The standing height measurements were performed at the same time of the day by using a wallmounted device (e.g. Harpenden Stadiometer) at each study visit. The pre-specified clinical outcomes were analyzed at 12 and 24 months.
Time frame: Baseline, 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children with evaluable height data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change in Height From Baseline | 12 Months | 9.0 centimeters (cm) | Standard Deviation 1.3 |
| Genotonorm | Change in Height From Baseline | 24 Months | 16.4 centimeters (cm) | Standard Deviation 2.2 |
Other Pre-specified
Growth Rate at 12 and 24 Months
Growth Rate was calculated at 12 months as: (Height at 12 months minus Height at Day 0) divided by {(Date of 12 months minus Date of Day 0) divided by 365.25} Growth Rate was calculated at 24 months as: (Height at 24 months minus Height at 12 months) divided by {(Date of 24 months minus Date of 12 months) divided by 365.25}
Time frame: 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children treated. n = Number of children with evaluable growth rate data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Growth Rate at 12 and 24 Months | 12 Months | 9.06 cm/year | Standard Deviation 1.4 |
| Genotonorm | Growth Rate at 12 and 24 Months | 24 Months (n=55) | 7.23 cm/year | Standard Deviation 1.38 |
Other Pre-specified
Summary of Body Mass Index (BMI) at 12 and 24 Months
BMI was calculated at 12 months and 24 months as: (Weight at 12 or 24 months divided by Height at 12 or 24 months) squared
Time frame: 12 and 24 months
Population: FAS. Number of Participants Analyzed = Number of children treated. n = Number of children with evaluable BMI data at 12 and 24 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Summary of Body Mass Index (BMI) at 12 and 24 Months | 12 Months (n=54) | 14.7 kg/meters squared (m2) | Standard Deviation 1.5 |
| Genotonorm | Summary of Body Mass Index (BMI) at 12 and 24 Months | 24 Months (n=55) | 14.9 kg/meters squared (m2) | Standard Deviation 1.4 |