Trial Outcomes & Findings for Study Aimed At Improving Height With Genotonorm In Children Born Little And/Or Light With Growth Retardation At The Age (NCT NCT00174252)
NCT ID: NCT00174252
Last Updated: 2010-06-15
Results Overview
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.
COMPLETED
PHASE3
57 participants
9 and 12 months
2010-06-15
Participant Flow
Participant milestones
| Measure |
Genotonorm
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
|---|---|
|
Overall Study
STARTED
|
57
|
|
Overall Study
COMPLETED
|
55
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Genotonorm
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
|---|---|
|
Overall Study
Protocol Violation
|
2
|
Baseline Characteristics
Study Aimed At Improving Height With Genotonorm In Children Born Little And/Or Light With Growth Retardation At The Age
Baseline characteristics by cohort
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
|---|---|
|
Age, Customized
<4 years
|
1 participants
n=99 Participants
|
|
Age, Customized
Between 4 and 8 years
|
49 participants
n=99 Participants
|
|
Age, Customized
Between 8 and 12 years
|
7 participants
n=99 Participants
|
|
Age, Customized
>=12 years
|
0 participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 9 and 12 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: Baseline, 12 monthsPopulation: 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.
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".
Outcome measures
| Measure |
Genotonorm
n=46 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 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
|
0.81 SD for CA
Standard Deviation 0.26
|
—
|
SECONDARY outcome
Timeframe: Baseline, 24 monthsPopulation: 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.
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".
Outcome measures
| Measure |
Genotonorm
n=47 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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 outcome
Timeframe: Baseline, 12 and 24 monthsPopulation: 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.
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".
Outcome measures
| Measure |
Genotonorm
n=8 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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
|
—
|
|
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 0.20
|
—
|
SECONDARY outcome
Timeframe: Baseline, 12 monthsPopulation: 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.
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".
Outcome measures
| Measure |
Genotonorm
n=33 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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 outcome
Timeframe: Baseline, 24 monthsPopulation: 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.
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".
Outcome measures
| Measure |
Genotonorm
n=31 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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 outcome
Timeframe: Baseline, 12 and 24 monthsPopulation: 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.
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".
Outcome measures
| Measure |
Genotonorm
n=7 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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 1.30
|
—
|
|
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 outcome
Timeframe: 12 and 24 monthsPopulation: 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.
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
Outcome measures
| Measure |
Genotonorm
n=49 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 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 Months
|
3.77 SD for CA
Standard Deviation 1.68
|
—
|
|
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 outcome
Timeframe: 12 and 24 monthsPopulation: 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.
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
Outcome measures
| Measure |
Genotonorm
n=8 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 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 Months
|
5.24 SD for CA
Standard Deviation 1.64
|
—
|
|
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 outcome
Timeframe: Baseline, 12 monthsPopulation: 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.
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
Outcome measures
| Measure |
Genotonorm
n=33 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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 outcome
Timeframe: Baseline, 24 monthsPopulation: 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.
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
Outcome measures
| Measure |
Genotonorm
n=39 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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 outcome
Timeframe: 12 and 24 monthsPopulation: 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.
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
Outcome measures
| Measure |
Genotonorm
n=7 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 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 Months
|
4.02 SD for BA
Standard Deviation 2.37
|
—
|
|
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 outcome
Timeframe: Baseline, 12 monthsPopulation: 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.
Change in Height SD (CA) was calculated as: Height SD (CA) at 12 months minus Height SD (CA) at Baseline
Outcome measures
| Measure |
Genotonorm
n=46 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
n=8 Participants
|
|---|---|---|
|
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
|
-1.59 SD for CA
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline, 24 monthsPopulation: 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.
Height SD (CA) at 24 months.
Outcome measures
| Measure |
Genotonorm
n=44 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
n=8 Participants
|
|---|---|---|
|
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
|
-1.18 SD for CA
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline, 12 monthsPopulation: 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.
Change in Height SD (BA) was calculated as: Height SD (BA) at 12 months minus Height SD (BA) at Baseline
Outcome measures
| Measure |
Genotonorm
n=33 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
n=7 Participants
|
|---|---|---|
|
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
|
0.76 SD for BA
Standard Error 0.48
|
SECONDARY outcome
Timeframe: Baseline, 24 monthsPopulation: 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.
Height SD (BA) at 24 months
Outcome measures
| Measure |
Genotonorm
n=31 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
n=7 Participants
|
|---|---|---|
|
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
|
0.64 SD for BA
Standard Error 0.53
|
SECONDARY outcome
Timeframe: 6, 9, 12, 15, 18, 21, and 24 monthsPopulation: 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.
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
Outcome measures
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 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
9 Months (n=46)
|
0.93 SD
Standard Deviation 1.26
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: 6, 9, 12, 15, 18, 21, and 24 monthsPopulation: 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.
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
Outcome measures
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 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 and 12 Months
6 Months (n=7)
|
2.32 SD
Standard Deviation 0.68
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: 12 and 24 monthsPopulation: 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.
Outcome measures
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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
|
—
|
|
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 outcome
Timeframe: 12 and 24 monthsPopulation: 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.
Outcome measures
| Measure |
Genotonorm
n=8 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 12 and 24 monthsPopulation: FAS. Number of Participants Analyzed = Number of children with evaluable height data at 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.
Outcome measures
| Measure |
Genotonorm
n=55 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
Change in Height From Baseline
12 Months
|
9.0 centimeters (cm)
Standard Deviation 1.3
|
—
|
|
Change in Height From Baseline
24 Months
|
16.4 centimeters (cm)
Standard Deviation 2.2
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 and 24 monthsPopulation: FAS. Number of Participants Analyzed = Number of children treated. n = Number of children with evaluable growth rate data 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}
Outcome measures
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
Growth Rate at 12 and 24 Months
12 Months
|
9.06 cm/year
Standard Deviation 1.40
|
—
|
|
Growth Rate at 12 and 24 Months
24 Months (n=55)
|
7.23 cm/year
Standard Deviation 1.38
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 and 24 monthsPopulation: FAS. Number of Participants Analyzed = Number of children treated. n = Number of children with evaluable BMI data 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
Outcome measures
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 12 and 24 monthsPopulation: FAS. Number of Participants Analyzed = Number of children treated. n = Number of children with evaluable BA data at 12 and 24 months.
Change in BA was calculated as: (12 or 24 months minus Screening)
Outcome measures
| Measure |
Genotonorm
n=57 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
Change in BA From Baseline at 12 and 24 Months
12 Months (n=33)
|
1.2 year
Standard Deviation 0.9
|
—
|
|
Change in BA From Baseline at 12 and 24 Months
24 Months (n=31)
|
2.5 year
Standard Deviation 1.1
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 and 24 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Genotonorm
n=43 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 and 24 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Genotonorm
n=7 Participants
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
Genotonorm (IGF-1 > 2 SD at 9 and 12 Months)
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
Adverse Events
Genotonorm
Serious adverse events
| Measure |
Genotonorm
n=57 participants at risk
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
|---|---|
|
Congenital, familial and genetic disorders
Amniotic band syndrome
|
1.8%
1/57
|
|
Ear and labyrinth disorders
Deafness
|
1.8%
1/57
|
|
Infections and infestations
Pneumonia
|
1.8%
1/57
|
|
Infections and infestations
Staphylococcal infection
|
1.8%
1/57
|
|
Renal and urinary disorders
Dysuria
|
1.8%
1/57
|
|
Renal and urinary disorders
Haematuria
|
1.8%
1/57
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
1.8%
1/57
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
|
1.8%
1/57
|
Other adverse events
| Measure |
Genotonorm
n=57 participants at risk
Initiated at a dose of 0.40 milligrams (mg)/kilograms (kg) of Genotonorm divided in 7 daily subcutaneous injections and titrated as needed.
|
|---|---|
|
Blood and lymphatic system disorders
Microcytosis
|
1.8%
1/57
|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
1.8%
1/57
|
|
Eye disorders
Conjunctivitis
|
1.8%
1/57
|
|
Eye disorders
Conjunctivitis allergic
|
1.8%
1/57
|
|
Eye disorders
Eyelid oedema
|
1.8%
1/57
|
|
Gastrointestinal disorders
Constipation
|
7.0%
4/57
|
|
Gastrointestinal disorders
Diarrhoea
|
1.8%
1/57
|
|
General disorders
Fatigue
|
1.8%
1/57
|
|
General disorders
Pain
|
1.8%
1/57
|
|
General disorders
Pyrexia
|
1.8%
1/57
|
|
Immune system disorders
House dust allergy
|
1.8%
1/57
|
|
Infections and infestations
Bronchiolitis
|
1.8%
1/57
|
|
Infections and infestations
Bronchitis
|
8.8%
5/57
|
|
Infections and infestations
Ear infection
|
5.3%
3/57
|
|
Infections and infestations
Furuncle
|
1.8%
1/57
|
|
Infections and infestations
Gastroenteritis
|
5.3%
3/57
|
|
Infections and infestations
Influenza
|
1.8%
1/57
|
|
Infections and infestations
Laryngitis
|
1.8%
1/57
|
|
Infections and infestations
Lyme disease
|
1.8%
1/57
|
|
Infections and infestations
Nasopharyngitis
|
7.0%
4/57
|
|
Infections and infestations
Oral herpes
|
1.8%
1/57
|
|
Infections and infestations
Otitis media
|
1.8%
1/57
|
|
Infections and infestations
Pharyngitis
|
1.8%
1/57
|
|
Infections and infestations
Pneumonia
|
1.8%
1/57
|
|
Infections and infestations
Rhinitis
|
7.0%
4/57
|
|
Infections and infestations
Skin infection
|
1.8%
1/57
|
|
Infections and infestations
Tinea infection
|
1.8%
1/57
|
|
Infections and infestations
Tonsillitis
|
3.5%
2/57
|
|
Infections and infestations
Upper respiratory tract infection
|
1.8%
1/57
|
|
Infections and infestations
Varicella
|
10.5%
6/57
|
|
Infections and infestations
Viral infection
|
1.8%
1/57
|
|
Infections and infestations
Vulvitis
|
1.8%
1/57
|
|
Investigations
Insulin-like growth factor increased
|
5.3%
3/57
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.8%
1/57
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.5%
2/57
|
|
Nervous system disorders
Headache
|
8.8%
5/57
|
|
Psychiatric disorders
Sleep disorder
|
1.8%
1/57
|
|
Psychiatric disorders
Sleep terror
|
1.8%
1/57
|
|
Renal and urinary disorders
Enuresis
|
1.8%
1/57
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.3%
3/57
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
1.8%
1/57
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
|
1.8%
1/57
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
1.8%
1/57
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
1.8%
1/57
|
|
Skin and subcutaneous tissue disorders
Eczema
|
1.8%
1/57
|
|
Skin and subcutaneous tissue disorders
Lipodystrophy acquired
|
1.8%
1/57
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.8%
1/57
|
|
Surgical and medical procedures
Adenotonsillectomy
|
1.8%
1/57
|
|
Surgical and medical procedures
Tonsillectomy
|
1.8%
1/57
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER