Growth Hormone Deficiency
Conditions
Brief summary
To estimate the evolution of height and growth rate over 5 years of growth hormone (GH) treatment To estimate the prognostic factors of growth rate with GH treatment To confirm the good clinical and biological safety of GH treatment in such children
Interventions
DRUGSomatropin
Liquid, daily, during 3 years and extended to 5 years Dosage: 0,46 mg/kg/week - the maximum dose should not exceed 50 µg/kg/day
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Glucocorticosteroid treatment for 12 months at least * Bone age \< 15 years for a boy and \< 13 years for a girl * Child measured height \< - 2 SD, Child currently treated by GH
Exclusion criteria
* Known diabetes (type 1 or type 2) * A previous history of intolerance or hypersensitivity to the study drug or to drugs with similar chemical structures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36: Full Analysis Population | Baseline, 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; Yx refers to the value at particular timepoint x. 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. |
| Change From Baseline in Height Standard Deviation Score (SD) for Chronological Age (CA) at Month 36: Per Protocol (PP) Population | Baseline, 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; Yx refers to the value at particular timepoint x. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Growth Rate (GR) Standard Deviation Score (SDS) for Bone Age (BA) | Month 12, 24, 36, 48, 60 | GR SDS BA Yx = (GR Yx - reference mean for BA Yx) / reference SD for BA Yx; Yx refers to the value at particular timepoint x. GR in SDS was calculated using Sempe reference means and SD for GR. BA was estimated locally using an X-ray from the left wrist and hand. |
| Body Mass Index (BMI) | Baseline, Month 12, 24, 36, 48, 60 | BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). |
| Change From Baseline in Height at Month 12, 24, 36, 48 and 60 | Baseline, Month 12, 24, 36, 48, 60 | The standing height measurements were performed 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 Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, 24, 48 and 60 | Baseline, Month 12, 24, 48, 60 | The standing height measurements were performed 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; Yx refers to the value at particular timepoint x. 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. |
| Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Baseline, Month 12, 24, 36, 48, 60 | The standing height measurements were performed 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 BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx; Yx refers to the value at particular timepoint x. 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. |
| Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Baseline, Month 12, 24, 36, 48, 60 | 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, 24, 36, 48, 60 | 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. |
| Mean Height | Baseline, Month 12, 24, 36, 48, 60 | The standing height measurements were performed 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 Bone Age (BA) | Baseline, Month 12, 24, 36, 48, 60 | The standing height measurements were performed 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 BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx; Yx refers to the value at particular timepoint x. 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. |
| Annual Growth Rate (AGR) | Baseline, Month 12, 24, 36, 48, 60 | AGR at Yx was derived by subtracting AGR at baseline from Yx value. AGR was calculated each year and re scaled 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). Yx refers to the value at particular timepoint x. |
| Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA) | Baseline, Month 12, 24, 36, 48, 60 | GR SDS CA Yx = (GR Yx - reference mean for CA Yx) / reference SD for CA Yx; Yx refers to the value at particular timepoint x. GR in SDS was calculated using Sempe reference means and SD for GR. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Received Concomitant Medications | Baseline up to Month 60 | — |
| Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Screening, Month 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 | — |
| Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Screening, Month 12, 24, 36, 48, 60 | Fasting and 2 hours plasma glucose levels were assessed using standard oral glucose tolerance test (OGTT). |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline up to 28 days after last study treatment | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs include both SAEs and non-SAEs. |
| Number of Participants With Significant Changes in Physical Examinations | Baseline, Month 12, 24, 36, 48, 60, End of Treatment (EOT) | Number of participants with clinically significant physical examinations changes since previous visit were reported. Physical examination including estimation of pubertal stage and blood pressure measurement; |
| Number of Participants With at Least 1 Medical or Surgical History | Screening | — |
Countries
France
Participant flow
Pre-assignment details
The reason 'Study Terminated by Sponsor' mentioned in the participant flow indicates the termination of study at a site (due to Good Clinical Practice \[GCP\] compliance issues) and does not reflect the overall status of study.
Participants by arm
| Arm | Count |
|---|---|
| Genotonorm Genotonorm 0.46 milligram per kilogram (mg/kg) administered weekly, divided into 7 daily subcutaneous injections (maximum dose not exceeding 50 microgram \[mcg\]/kg/day) for up to 60 months. | 98 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Death | 3 |
| Overall Study | Did not meet continuation criterion | 16 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 6 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Study terminated by sponsor | 11 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Genotonorm |
|---|---|
| Age, Continuous | 11.8 years STANDARD_DEVIATION 3.2 |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 81 / 98 |
| serious Total, serious adverse events | 45 / 98 |
Outcome results
Primary
Change From Baseline in Height Standard Deviation Score (SD) for Chronological Age (CA) at Month 36: Per Protocol (PP) Population
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; Yx refers to the value at particular timepoint x. 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.
Time frame: Baseline, Month 36
Population: PP analysis set included all participants (excluding a site with GCP issues) who received at least 1 dose of GH, had at least 1 subsequent rating of height, no major protocol violation till first 3 years post initiation of treatment and total GH treatment duration of 36 months or more. n=participants evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SD) for Chronological Age (CA) at Month 36: Per Protocol (PP) Population | Baseline (n=21) | -2.86 SDS | Standard Deviation 0.89 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SD) for Chronological Age (CA) at Month 36: Per Protocol (PP) Population | Change at Month 36 (n=19) | 0.81 SDS | Standard Deviation 1.18 |
Comparison: Month 36p-value: 0.008Student's paired t-test
Primary
Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36: Full Analysis Population
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; Yx refers to the value at particular timepoint x. 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.
Time frame: Baseline, Month 36
Population: Full analysis set (FAS) included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36: Full Analysis Population | Baseline (n=58) | -2.91 Standard Deviation Score (SDS) | Standard Deviation 1.19 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36: Full Analysis Population | Change at Month 36 (n=30) | 0.80 Standard Deviation Score (SDS) | Standard Deviation 1.03 |
Comparison: Month 36p-value: <0.001Student's paired t-test
Secondary
Annual Growth Rate (AGR)
AGR at Yx was derived by subtracting AGR at baseline from Yx value. AGR was calculated each year and re scaled 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). Yx refers to the value at particular timepoint x.
Time frame: Baseline, Month 12, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Annual Growth Rate (AGR) | Baseline (n=52) | 3.0 cm/year | Standard Deviation 2 |
| Genotonorm | Annual Growth Rate (AGR) | Month 12 (n=49) | 6.7 cm/year | Standard Deviation 2.6 |
| Genotonorm | Annual Growth Rate (AGR) | Month 24 (n=41) | 6.0 cm/year | Standard Deviation 2.7 |
| Genotonorm | Annual Growth Rate (AGR) | Month 36 (n=30) | 5.9 cm/year | Standard Deviation 2.7 |
| Genotonorm | Annual Growth Rate (AGR) | Month 48 (n=14) | 4.8 cm/year | Standard Deviation 2.5 |
| Genotonorm | Annual Growth Rate (AGR) | Month 60 (n=9) | 4.9 cm/year | Standard Deviation 3 |
Secondary
Body Mass Index (BMI)
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2).
Time frame: Baseline, Month 12, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Body Mass Index (BMI) | Month 60 (n=9) | 20.8 kg/m^2 | Standard Deviation 3.3 |
| Genotonorm | Body Mass Index (BMI) | Baseline (n=58) | 19.4 kg/m^2 | Standard Deviation 3.6 |
| Genotonorm | Body Mass Index (BMI) | Month 12 (n=50) | 19.1 kg/m^2 | Standard Deviation 3.1 |
| Genotonorm | Body Mass Index (BMI) | Month 24 (n=41) | 19.4 kg/m^2 | Standard Deviation 3 |
| Genotonorm | Body Mass Index (BMI) | Month 36 (n=30) | 19.4 kg/m^2 | Standard Deviation 2.4 |
| Genotonorm | Body Mass Index (BMI) | Month 48 (n=14) | 19.7 kg/m^2 | Standard Deviation 3 |
Secondary
Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60
BA was estimated locally using an X-ray from the left wrist and hand.
Time frame: Baseline, Month 12, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 48 (n=13) | 52.8 months | Standard Deviation 21.2 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Baseline (n=58) | 117.9 months | Standard Deviation 34.6 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 12 (n=37) | 17.8 months | Standard Deviation 11 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 24 (n=32) | 28.2 months | Standard Deviation 17.9 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 36 (n=23) | 36.5 months | Standard Deviation 17.8 |
| Genotonorm | Change From Baseline in Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 60 (n=7) | 70.0 months | Standard Deviation 27 |
Secondary
Change From Baseline in Height at Month 12, 24, 36, 48 and 60
The standing height measurements were performed 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, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Change From Baseline in Height at Month 12, 24, 36, 48 and 60 | Baseline (n=58) | 133.9 cm | Standard Deviation 15.7 |
| Genotonorm | Change From Baseline in Height at Month 12, 24, 36, 48 and 60 | Change at Month 12 (n=50) | 6.8 cm | Standard Deviation 2.8 |
| Genotonorm | Change From Baseline in Height at Month 12, 24, 36, 48 and 60 | Change at Month 24 (n=41) | 12.9 cm | Standard Deviation 4.7 |
| Genotonorm | Change From Baseline in Height at Month 12, 24, 36, 48 and 60 | Change at Month 36 (n=30) | 18.8 cm | Standard Deviation 6.1 |
| Genotonorm | Change From Baseline in Height at Month 12, 24, 36, 48 and 60 | Change at Month 48 (n=14) | 23.9 cm | Standard Deviation 8.5 |
| Genotonorm | Change From Baseline in Height at Month 12, 24, 36, 48 and 60 | Change at Month 60 (n=9) | 30.3 cm | Standard Deviation 7.6 |
Secondary
Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, 24, 36, 48 and 60
The standing height measurements were performed 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 BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx; Yx refers to the value at particular timepoint x. 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.
Time frame: Baseline, Month 12, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified 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, 24, 36, 48 and 60 | Baseline (n=51) | -0.29 SDS | Standard Deviation 1.15 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 12 (n=36) | -0.02 SDS | Standard Deviation 0.99 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 24 (n=26) | 0.28 SDS | Standard Deviation 1.18 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 36 (n=21) | 0.31 SDS | Standard Deviation 1.17 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 48 (n=13) | -0.08 SDS | Standard Deviation 1.3 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, 24, 36, 48 and 60 | Change at Month 60 (n=7) | 0.01 SDS | Standard Deviation 1.33 |
Secondary
Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, 24, 48 and 60
The standing height measurements were performed 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; Yx refers to the value at particular timepoint x. 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.
Time frame: Baseline, Month 12, 24, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified 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, 24, 48 and 60 | Baseline (n=58) | -2.91 SDS | Standard Deviation 1.19 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, 24, 48 and 60 | Change at Month 12 (n=50) | 0.28 SDS | Standard Deviation 0.57 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, 24, 48 and 60 | Change at Month 24 (n=41) | 0.57 SDS | Standard Deviation 0.95 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, 24, 48 and 60 | Change at Month 48 (n=14) | 0.82 SDS | Standard Deviation 1.42 |
| Genotonorm | Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, 24, 48 and 60 | Change at Month 60 (n=9) | 0.75 SDS | Standard Deviation 1.13 |
Secondary
Growth Rate (GR) Standard Deviation Score (SDS) for Bone Age (BA)
GR SDS BA Yx = (GR Yx - reference mean for BA Yx) / reference SD for BA Yx; Yx refers to the value at particular timepoint x. GR in SDS was calculated using Sempe reference means and SD for GR. BA was estimated locally using an X-ray from the left wrist and hand.
Time frame: Month 12, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Bone Age (BA) | Month 12 (n=36) | -0.13 SDS | Standard Deviation 2.15 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Bone Age (BA) | Month 24 (n=25) | 0.07 SDS | Standard Deviation 2.51 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Bone Age (BA) | Month 36 (n=20) | 0.05 SDS | Standard Deviation 1.94 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Bone Age (BA) | Month 48 (n=11) | -1.00 SDS | Standard Deviation 1.38 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Bone Age (BA) | Month 60 (n=7) | -0.43 SDS | Standard Deviation 1.22 |
Secondary
Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA)
GR SDS CA Yx = (GR Yx - reference mean for CA Yx) / reference SD for CA Yx; Yx refers to the value at particular timepoint x. GR in SDS was calculated using Sempe reference means and SD for GR. CA calculated as integer (Date of height measurement-Date of birth)/365.25\*12.
Time frame: Baseline, Month 12, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA) | Baseline (n=52) | -2.04 SDS | Standard Deviation 2.03 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA) | Month 12 (n=49) | 1.77 SDS | Standard Deviation 4.29 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA) | Month 24 (n=41) | 5.26 SDS | Standard Deviation 16.79 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA) | Month 36 (n=29) | 3.64 SDS | Standard Deviation 9.06 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA) | Month 48 (n=13) | 0.93 SDS | Standard Deviation 2.73 |
| Genotonorm | Growth Rate (GR) Standard Deviation Score (SDS) for Chronological Age (CA) | Month 60 (n=9) | 1.40 SDS | Standard Deviation 1.71 |
Secondary
Mean Height
The standing height measurements were performed 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, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Mean Height | Baseline (n=58) | 133.9 centimeters (cm) | Standard Deviation 15.7 |
| Genotonorm | Mean Height | Month 12 (n=50) | 139.5 centimeters (cm) | Standard Deviation 16.8 |
| Genotonorm | Mean Height | Month 24 (n=41) | 146.0 centimeters (cm) | Standard Deviation 16.4 |
| Genotonorm | Mean Height | Month 36 (n=30) | 150.4 centimeters (cm) | Standard Deviation 16 |
| Genotonorm | Mean Height | Month 48 (n=14) | 152.4 centimeters (cm) | Standard Deviation 16 |
| Genotonorm | Mean Height | Month 60 (n=9) | 156.0 centimeters (cm) | Standard Deviation 11.3 |
Secondary
Mean Height Standard Deviation Score (SDS) for Bone Age (BA)
The standing height measurements were performed 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 BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx; Yx refers to the value at particular timepoint x. 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.
Time frame: Baseline, Month 12, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Baseline (n=51) | -0.29 SDS | Standard Deviation 1.15 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 12 (n=40) | -0.36 SDS | Standard Deviation 1.52 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 24 (n=29) | 0.11 SDS | Standard Deviation 1.36 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 36 (n=24) | 0.14 SDS | Standard Deviation 1.48 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 48 (n=13) | -0.26 SDS | Standard Deviation 1.28 |
| Genotonorm | Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Month 60 (n=7) | -0.19 SDS | Standard Deviation 1.15 |
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, 24, 36, 48, 60
Population: FAS included all participants (excluding a site with GCP issues) who had received at least 1 injection of GH and had at least 1 post-Baseline measurement of height. Here n signifies those participants who were evaluable for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 24 (n=32) | 0.80 ratio | Standard Deviation 0.09 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Baseline (n=58) | 0.78 ratio | Standard Deviation 0.1 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 12 (n=37) | 0.82 ratio | Standard Deviation 0.11 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 36 (n=23) | 0.79 ratio | Standard Deviation 0.1 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 48 (n=13) | 0.81 ratio | Standard Deviation 0.08 |
| Genotonorm | Ratio of Bone Age (BA) to Chronological Age (CA) | Month 60 (n=7) | 0.85 ratio | Standard Deviation 0.1 |
Other Pre-specified
Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60
Fasting and 2 hours plasma glucose levels were assessed using standard oral glucose tolerance test (OGTT).
Time frame: Screening, Month 12, 24, 36, 48, 60
Population: Safety analysis set included all participants (including a site with GCP issues) who had received at least 1 study dose of GH.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Fasting: Screening (n=91) | 4.5 milli mole per liter (mmol/L) | Standard Deviation 0.7 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Fasting: Month 12 (n=69) | 4.6 milli mole per liter (mmol/L) | Standard Deviation 0.7 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Fasting: Month 24 (n=59) | 4.7 milli mole per liter (mmol/L) | Standard Deviation 0.6 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Fasting: Month 36 (n=45) | 4.6 milli mole per liter (mmol/L) | Standard Deviation 0.5 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Fasting: Month 48 (n=20) | 4.7 milli mole per liter (mmol/L) | Standard Deviation 0.4 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Fasting: Month 60 (n=14) | 4.5 milli mole per liter (mmol/L) | Standard Deviation 0.6 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Postprandial: Screening (n=94) | 5.6 milli mole per liter (mmol/L) | Standard Deviation 1.2 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Postprandial: Month 12 (n=66) | 6.1 milli mole per liter (mmol/L) | Standard Deviation 1.4 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Postprandial: Month 24 (n=59) | 6.1 milli mole per liter (mmol/L) | Standard Deviation 1.4 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Postprandial: Month 36 (n=41) | 6.4 milli mole per liter (mmol/L) | Standard Deviation 1.6 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Postprandial: Month 48 (n=19) | 6.1 milli mole per liter (mmol/L) | Standard Deviation 1.1 |
| Genotonorm | Fasting and Postprandial Plasma Glucose Levels at Month 12, 24, 36, 48 and 60 | Glucose Postprandial: Month 60 (n=13) | 6.3 milli mole per liter (mmol/L) | Standard Deviation 1.5 |
Other Pre-specified
Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels
Time frame: Screening, Month 6, 12, 18, 24, 30, 36, 42, 48, 54, 60
Population: Safety analysis set included all participants (including a site with GCP issues) who had received at least 1 study dose of GH.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Screening (n=93) | 335 nanogram per milliliter (ng/mL) | Standard Deviation 157 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 6 (n=63) | 604 nanogram per milliliter (ng/mL) | Standard Deviation 291 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 12 (n=71) | 538 nanogram per milliliter (ng/mL) | Standard Deviation 268 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 18 (n=47) | 624 nanogram per milliliter (ng/mL) | Standard Deviation 251 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 24 (n=62) | 579 nanogram per milliliter (ng/mL) | Standard Deviation 262 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 30 (n=50) | 559 nanogram per milliliter (ng/mL) | Standard Deviation 250 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 36 (n=44) | 511 nanogram per milliliter (ng/mL) | Standard Deviation 186 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 42 (n=22) | 555 nanogram per milliliter (ng/mL) | Standard Deviation 224 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 48 (n=21) | 581 nanogram per milliliter (ng/mL) | Standard Deviation 244 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 54 (n=16) | 593 nanogram per milliliter (ng/mL) | Standard Deviation 184 |
| Genotonorm | Fasting Serum Insulin Like Growth Factor-1 (IGF-1) Levels | Month 60 (n=10) | 501 nanogram per milliliter (ng/mL) | Standard Deviation 180 |
Other Pre-specified
Number of Participants Who Received Concomitant Medications
Time frame: Baseline up to Month 60
Population: Safety analysis set included all participants (including a site with GCP issues) who had received at least 1 study dose of GH.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotonorm | Number of Participants Who Received Concomitant Medications | 98 participants |
Other Pre-specified
Number of Participants With at Least 1 Medical or Surgical History
Time frame: Screening
Population: Safety analysis set included all participants (including a site with GCP issues) who had received at least 1 study dose of GH.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotonorm | Number of Participants With at Least 1 Medical or Surgical History | 67 participants |
Other Pre-specified
Number of Participants With Significant Changes in Physical Examinations
Number of participants with clinically significant physical examinations changes since previous visit were reported. Physical examination including estimation of pubertal stage and blood pressure measurement;
Time frame: Baseline, Month 12, 24, 36, 48, 60, End of Treatment (EOT)
Population: Safety analysis set included all participants (including a site with GCP issues) who had received at least 1 study dose of GH.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotonorm | Number of Participants With Significant Changes in Physical Examinations | Baseline (n=93) | 1 participants |
| Genotonorm | Number of Participants With Significant Changes in Physical Examinations | Month 12 (n=93) | 16 participants |
| Genotonorm | Number of Participants With Significant Changes in Physical Examinations | Month 24 (n=72) | 16 participants |
| Genotonorm | Number of Participants With Significant Changes in Physical Examinations | Month 36 (n=52) | 5 participants |
| Genotonorm | Number of Participants With Significant Changes in Physical Examinations | Month 48 (n=23) | 4 participants |
| Genotonorm | Number of Participants With Significant Changes in Physical Examinations | Month 60 (n=12) | 2 participants |
| Genotonorm | Number of Participants With Significant Changes in Physical Examinations | EOT (n=44) | 11 participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs include both SAEs and non-SAEs.
Time frame: Baseline up to 28 days after last study treatment
Population: Safety analysis set included all participants (including a site with GCP issues) who had received at least 1 study dose of GH.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotonorm | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 84 participants |
| Genotonorm | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 45 participants |