Endocrine System Diseases
Conditions
Brief summary
To show an increase in annual growth rate 3 years after Visit 2. Annual growth rate in standard deviation (SD) after 3 years will be compared to growth rate before the start of GH treatment.
Interventions
DRUGSomatropin
Adapted dosage based on IGF 1 level and weight Form: liquid; Dosage and Frequency: from 0.0033mg/kg/day to 0.0067 mg/kg/day; Duration: 3 years
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 13 Years
Healthy volunteers
No
Inclusion criteria
* Bone age \< 13 years for a boy and \< 11 years for a girl * Naive child: Measured Height \< -2.5 SD for CA * Child currently treated by GH
Exclusion criteria
* Idiopathic short stature * Syndrome known to be associated with an increased risk of cancer e.g. family history of adenomatous polyposis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Intent-to-Treat (ITT) Population | Baseline, Month 36 | Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population. |
| Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Per-Protocol (PP) Population | Baseline, Month 36 | Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Height | Baseline, Month 12, Month 24, Month 36 | Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. |
| Change From Baseline in Height at Month 12, Month 24 and Month 36 | Baseline, Month 12, Month 24, Month 36 | Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. |
| Mean Height Standard Deviation Score (SDS) for Chronological Age (CA) | Baseline, Month 12, Month 24, Month 36 | Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. Height SDS CA Yx = (height Yx - reference mean for CA Yx) / reference SD for CA Yx. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36 | Baseline, Month 12, Month 24, Month 36 | Change in height SDS CA was derived by subtracting height SDS CA at baseline from Yx value. Height SDS CA (for both baseline and Yx) = (height - reference mean for CA)/reference SD for CA. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement - Date of birth)/365.25\*12. SDS indicates how similar the participant was to the reference population. |
| Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Baseline, Month 12, Month 24, Month 36 | Height SDS BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36 | Baseline, Month 12, Month 24, Month 36 | Change in height SDS BA was derived by subtracting height SDS BA at baseline from Yx value. Height SDS BA (for both baseline and Yx) = (height-reference mean for BA)/reference SD for BA. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population | Baseline, Month 12, Month 24, Month 36 | Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y\[x-1\] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y\[x-1\]) and height recorded at Yx (AGR Yx = \[height Yx-height Y{x-1}\] / (\[date of Yx - date of Y{x-1}\] /365.25). |
| Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in PP Population | Baseline, Month 12, Month 24 | Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population. |
| Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA) | Month 12, Month 24, Month 36 | AGR at Yx was derived by subtracting AGR at baseline from Yx value. AGR was calculated each year and rescaled to 1 year if the interval between Yx and Y\[x-1\] was not 365 days, as long as a participant remained in the study. AGR at Yx = \[height Yx-height Y{x-1}\] / (\[date of Yx - date of Y{x-1}\] /365.25). GR in SDS was calculated using Sempe reference means and SD for growth. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population. |
| Body Mass Index (BMI) | Baseline, Month 12, Month 24, Month 36 | BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared. |
| Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36 | Baseline, Month 12, Month 24, Month 36 | BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared. |
| Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36 | Baseline, Month 12, Month 24, Month 36 | BA was estimated locally using an X-ray from the left wrist and hand. |
| Ratio of Bone Age (BA) to Chronological Age (CA) | Baseline, Month 12, Month 24, Month 36 | BA was estimated locally using an X-ray from the left wrist and hand. CA at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA at each annual study visit was calculated. |
| Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in ITT Population | Baseline, Month 12, Month 24 | Change in AGR SDS for CA derived by subtracting AGR SDS CA at baseline from Yx value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population. |
| Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population | Baseline, Month 12, Month 24, Month 36 | Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y\[x-1\] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y\[x-1\]) and height recorded at Yx (AGR Yx = \[height Yx-height Y{x-1}\] / (\[date of Yx - date of Y{x-1}\] /365.25). |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Genotonorm Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Other | 7 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Genotonorm |
|---|---|
| Age Continuous | 10.3 years STANDARD_DEVIATION 3.6 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 46 |
| serious Total, serious adverse events | 4 / 46 |
Outcome results
Primary
Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Intent-to-Treat (ITT) Population
Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population.
Time frame: Baseline, Month 36
Population: Intent to Treat (ITT) set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Intent-to-Treat (ITT) Population | Change at Month 36 (n = 26) | 2.36 SDS | Standard Deviation 1.98 |
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Intent-to-Treat (ITT) Population | Baseline (n = 42) | -1.29 SDS | Standard Deviation 1.79 |
Primary
Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Per-Protocol (PP) Population
Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population.
Time frame: Baseline, Month 36
Population: Per Protocol (PP) analysis set included all participants in the ITT set without a major protocol violation. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Per-Protocol (PP) Population | Baseline (n = 14) | -1.98 SDS | Standard Deviation 1.06 |
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Per-Protocol (PP) Population | Change at Month 36 (n = 12) | 2.70 SDS | Standard Deviation 2.02 |
Secondary
Body Mass Index (BMI)
BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here n signifies those participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Body Mass Index (BMI) | Baseline (n = 44) | 16.57 kilogram per square meter (kg/m^2) | Standard Deviation 2.37 |
| Genotonorm | Body Mass Index (BMI) | Month 12 (n = 39) | 16.96 kilogram per square meter (kg/m^2) | Standard Deviation 2.64 |
| Genotonorm | Body Mass Index (BMI) | Month 24 (n = 39) | 17.59 kilogram per square meter (kg/m^2) | Standard Deviation 2.69 |
| Genotonorm | Body Mass Index (BMI) | Month 36 (n = 27) | 17.67 kilogram per square meter (kg/m^2) | Standard Deviation 2.08 |
Secondary
Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population
Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y\[x-1\] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y\[x-1\]) and height recorded at Yx (AGR Yx = \[height Yx-height Y{x-1}\] / (\[date of Yx - date of Y{x-1}\] /365.25).
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population | Change at Month 24 (n = 35) | 2.5 centimeter per year (cm/year) | Standard Deviation 2.7 |
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population | Baseline (n = 42) | 4.5 centimeter per year (cm/year) | Standard Deviation 1.8 |
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population | Change at Month 12 (n = 36) | 3.3 centimeter per year (cm/year) | Standard Deviation 2.9 |
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population | Change at Month 36 (n = 26) | 2.0 centimeter per year (cm/year) | Standard Deviation 2 |
Secondary
Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population
Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y\[x-1\] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y\[x-1\]) and height recorded at Yx (AGR Yx = \[height Yx-height Y{x-1}\] / (\[date of Yx - date of Y{x-1}\] /365.25).
Time frame: Baseline, Month 12, Month 24, Month 36
Population: PP analysis set included all participants in the ITT set without a major protocol violation. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population | Baseline (n = 14) | 4.0 cm/year | Standard Deviation 1 |
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population | Change at Month 12 (n = 14) | 4.0 cm/year | Standard Deviation 1 |
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population | Change at Month 24 (n = 14) | 2.5 cm/year | Standard Deviation 1.3 |
| Genotonorm | Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population | Change at Month 36 (n = 12) | 1.8 cm/year | Standard Deviation 1.1 |
Secondary
Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in ITT Population
Change in AGR SDS for CA derived by subtracting AGR SDS CA at baseline from Yx value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population.
Time frame: Baseline, Month 12, Month 24
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in ITT Population | Change at Month 12 (n = 36) | 3.23 SDS | Standard Deviation 2.66 |
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in ITT Population | Change at Month 24 (n = 35) | 2.62 SDS | Standard Deviation 2.05 |
Secondary
Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in PP Population
Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y\[x-1\])/(\[date of Yx-date of Y{x-1}\]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar participant was to reference population.
Time frame: Baseline, Month 12, Month 24
Population: PP analysis set included all participants in the ITT set without a major protocol violation. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in PP Population | Change at Month 24 (n = 14) | 2.97 SDS | Standard Deviation 1.68 |
| Genotonorm | Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in PP Population | Change at Month 12 (n = 14) | 4.40 SDS | Standard Deviation 2.12 |
Secondary
Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36
BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36 | Change at Month 12 (n = 39) | 0.52 kg/m^2 | Standard Deviation 1.01 |
| Genotonorm | Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36 | Change at Month 24 (n = 39) | 1.30 kg/m^2 | Standard Deviation 1.35 |
| Genotonorm | Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36 | Change at Month 36 (n = 27) | 1.89 kg/m^2 | Standard Deviation 1.61 |
Secondary
Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36
BA was estimated locally using an X-ray from the left wrist and hand.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36 | Change at Month 36 (n = 21) | 4.04 years | Standard Deviation 1.09 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36 | Baseline (n = 40) | 8.70 years | Standard Deviation 3.28 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36 | Change at Month 12 (n = 28) | 1.69 years | Standard Deviation 0.9 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36 | Change at Month 24 (n = 28) | 2.60 years | Standard Deviation 0.97 |
Secondary
Change From Baseline in Height at Month 12, Month 24 and Month 36
Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Height at Month 12, Month 24 and Month 36 | Change at Month 12 (n = 39) | 7.7 cm | Standard Deviation 2.1 |
| Genotonorm | Change From Baseline in Height at Month 12, Month 24 and Month 36 | Change at Month 24 (n = 39) | 14.9 cm | Standard Deviation 3.4 |
| Genotonorm | Change From Baseline in Height at Month 12, Month 24 and Month 36 | Change at Month 36 (n = 27) | 22.3 cm | Standard Deviation 3.7 |
Secondary
Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36
Change in height SDS BA was derived by subtracting height SDS BA at baseline from Yx value. Height SDS BA (for both baseline and Yx) = (height-reference mean for BA)/reference SD for BA. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36 | Change at Month 12 (n = 28) | -0.05 SDS | Standard Deviation 1.04 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36 | Change at Month 36 (n = 17) | 0.05 SDS | Standard Deviation 1.32 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36 | Change at Month 24 (n = 27) | 0.06 SDS | Standard Deviation 1.36 |
Secondary
Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36
Change in height SDS CA was derived by subtracting height SDS CA at baseline from Yx value. Height SDS CA (for both baseline and Yx) = (height - reference mean for CA)/reference SD for CA. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement - Date of birth)/365.25\*12. SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36 | Change at Month 12 (n = 39) | 0.41 SDS | Standard Deviation 0.42 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36 | Change at Month 24 (n = 39) | 0.81 SDS | Standard Deviation 0.6 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36 | Change at Month 36 (n = 27) | 1.03 SDS | Standard Deviation 0.62 |
Secondary
Height
Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here n signifies those participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Height | Baseline (n = 44) | 123.9 cm | Standard Deviation 17.3 |
| Genotonorm | Height | Month 12 (n = 39) | 130.3 cm | Standard Deviation 17.5 |
| Genotonorm | Height | Month 24 (n = 39) | 137.8 cm | Standard Deviation 16.9 |
| Genotonorm | Height | Month 36 (n = 27) | 143.5 cm | Standard Deviation 15.8 |
Secondary
Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA)
AGR at Yx was derived by subtracting AGR at baseline from Yx value. AGR was calculated each year and rescaled to 1 year if the interval between Yx and Y\[x-1\] was not 365 days, as long as a participant remained in the study. AGR at Yx = \[height Yx-height Y{x-1}\] / (\[date of Yx - date of Y{x-1}\] /365.25). GR in SDS was calculated using Sempe reference means and SD for growth. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.
Time frame: Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA) | Month 12 (n = 28) | 1.06 SDS | Standard Deviation 1.57 |
| Genotonorm | Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA) | Month 24 (n = 25) | 0.46 SDS | Standard Deviation 1.15 |
| Genotonorm | Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA) | Month 36 (n = 19) | -0.01 SDS | Standard Deviation 1.19 |
Secondary
Mean Height Standard Deviation Score (SDS) for Bone Age (BA)
Height SDS BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Baseline (n = 35) | -0.71 SDS | Standard Deviation 1.52 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 36 (n = 20) | -0.30 SDS | Standard Deviation 1.46 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 12 (n = 32) | -0.55 SDS | Standard Deviation 1.68 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 24 (n = 32) | -0.49 SDS | Standard Deviation 1.77 |
Secondary
Mean Height Standard Deviation Score (SDS) for Chronological Age (CA)
Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. Height SDS CA Yx = (height Yx - reference mean for CA Yx) / reference SD for CA Yx. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here n signifies those participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Chronological Age (CA) | Baseline (n = 44) | -2.84 SDS | Standard Deviation 0.91 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Chronological Age (CA) | Month 12 (n = 39) | -2.42 SDS | Standard Deviation 0.98 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Chronological Age (CA) | Month 36 (n = 27) | -1.72 SDS | Standard Deviation 0.96 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Chronological Age (CA) | Month 24 (n = 39) | -2.09 SDS | Standard Deviation 1.08 |
Secondary
Ratio of Bone Age (BA) to Chronological Age (CA)
BA was estimated locally using an X-ray from the left wrist and hand. CA at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA at each annual study visit was calculated.
Time frame: Baseline, Month 12, Month 24, Month 36
Population: ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and n signifies those participants evaluated at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Baseline (n = 40) | 0.79 ratio | Standard Deviation 0.15 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 12 (n = 30) | 0.83 ratio | Standard Deviation 0.15 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 24 (n = 32) | 0.85 ratio | Standard Deviation 0.12 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 36 (n = 23) | 0.89 ratio | Standard Deviation 0.14 |