Growth Hormone Therapy, Infant, Small for Gestational Age
Conditions
Brief summary
The planned study focuses on the effect of a one year Somatropin treatment (0.035 mg/kg/d or 0.067 mg/kg/d) in short children born SGA on neuromuscular function and cognitive performance.
Interventions
DRUGSomatropin
Patients will be randomized at baseline in a 1:1 ratio into treatment group or control group. After six months the control group will undergo GH therapy with a higher dose of 0.067 mg/kg/day, too. All patients are treated with growth hormone for 12 months.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
* Pre-pubertal boys between 6 and 10 years of age or girls between 6 and 9 years of age. * Birth length- and/or birth weight-SDS adjusted to gestational age \< -2.0 (Voigt et al. 2002, Voigt et al. 2006 or Lawrence et al. 1989). * Current height-SDS \< -2.5 (Brandt/Reinken 1992) and parental adjusted height-SDS below -1 (Hermanussen and Cole 2003). * Growth velocity SDS \< 0 during the last year before inclusion (Brandt/Reinken 1988).
Exclusion criteria
* Severe SGA (birth weight or length \< -4 SD) and clinically relevant dysmorphic features. * Severe pre-maturity (GA \< 32 weeks of gestation). * Severe perinatal complications like asphyxia, sepsis, necrotizing enterocolitis (NEC), respiratory distress syndrome, if associated with long-term sequelae (like short bowel syndrome, bronchopulmonary dysplasia (BPD), cerebral palsy etc). * Inability to perform one- or two leg jumps from a standing position. * Prior GH treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | Baseline and Month 6 | Vmax was measured by Leonardo Jumping Platform during two-leg jump. |
| Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | Baseline and Month 6 | Vmax was measured by Leonardo Jumping Platform during two-leg jump. |
| Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | Baseline and Month 6 | PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | Baseline and Month 6 | Peak jump power (PJP) was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | Baseline and Month 6 | PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | Baseline and Month 6 | PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Months 12 and 18 | Baseline, Month 12 and Month 18 | NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores\[sum of differences of correct {C} - incorrect {IC} Yes answers(1);sum of C Yes answers(2);sum of IC Yes answers(3);sum of differences of C-IC Yes answers with high associative items{ 87%-95%}(4);sum of differences of C-IC Yes answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)\].Scores were rated as below average(\<40), average(40-60), above average(\>60) and working time ranging between 9-12 minutes. |
| Change From Baseline in Intellectual Performance of Children Using Child Behavior Checklist 4-18 Years (CBCL 4-18) at Months 6, 12 and 18 | Baseline, Month 6, Month 12 and Month 18 | CBCL was standardized for children ages 4 to 18 years and measured child internalizing and externalizing behaviors and total problems. The 4-18 years' checklist contains 140 questions and responses were recorded on a Likert scale: 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. The range of possible values was 0-280 (0=good to 280=worst). |
| Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; One-leg-jump) at Months 6, 12 and 18 | Baseline, Month 6 , Month 12 and Month 18 | PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during one leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; One-leg-jump) at Months 6, 12 and 18 | Baseline, Month 6, Month 12 and Month 18 | PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during one leg jump. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Maximum Jump Velocity (Vmax; One-leg-jump) at Months 6, 12 and 18 | Baseline, Month 6, Month 12 and Month 18 | Vmax was measured by Leonardo Jumping Platform during one leg jump. |
| Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 | Baseline and Month 6 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity). |
| Change From Baseline in Five-chair Rising Test-Peak Jump Power (PJP) at Months 12 and 18 | Baseline, Month 12 and Month 18 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity). |
| Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 | Baseline and Month 6 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest. |
| Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Months 12 and 18 | Baseline, Month 12 and Month 18 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest. |
| Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 | Baseline and Month 6 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity. |
| Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Months 12 and 18 | Baseline, Month 12 and Month 18 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity. |
| Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Baseline and Month 6 | Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests. |
| Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Months 12 and 18 | Baseline, Month 12 and Month 18 | Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests. |
| Change From Baseline in One-chair Rising Test-Peak Jump Power (PJP) at Months 6, 12 and 18 | Baseline, Month 6 , Month 12 and Month 18 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJP is defined as the peak of the calculated power (force multiplied by velocity). |
| Change From Baseline in One-chair Rising Test-Peak Jump Force (PJF) at Months 6, 12 and 18 | Baseline, Month 6 , Month 12 and Month 18 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest. |
| Change From Baseline in One-chair Rising Test (Time to Perform the Tasks) at Months 6, 12 and 18 | Baseline, Month 6 , Month 12 and Month 18 | The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). |
| Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6 | Baseline and Month 6 | MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Months 12 and 18 | Baseline, Month 12 and Month 18 | MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population. |
| Mean Upper Arm Circumference | Baseline, Month 6, Month 12 and Month 18 | — |
| Mean Thigh Circumference | Baseline, Month 6, Month 12 and Month 18 | Thigh measurements were taken as a mean of 3 consecutive measurements at upper thigh about an inch down from the crotch line. |
| Mean Calf Circumference | Baseline, Month 6, Month 12 and Month 18 | Calf measurements were taken as a mean of 3 consecutive measurements at largest part of calf muscle, usually about 4 inches down from below the knee. |
| Mean Height at Month 6 | Month 6 | Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. |
| Mean Height at Months 12 and 18 | Month 12 and Month 18 | Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. |
| Mean Growth Velocity at Month 6 | Month 6 | Growth velocity measures the annual rate of increase in height. |
| Mean Growth Velocity at Months 12 and 18 | Month 12 and Month 18 | Growth velocity measures the annual rate of increase in height. |
| Mean Height-Standard Deviation Score (SDS) at Month 6 | Month 6 | Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population. |
| Mean Height-Standard Deviation Score (SDS) at Months 12 and 18 | Month 12 and Month 18 | Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population. |
| Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6 | Month 6 | Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population. |
| Mean Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18 | Month 12 and Month 18 | — |
| Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6 | Baseline and Month 6 | Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Height-Standard Deviation Score (SDS) at Months 12 and 18 | Baseline, Month 12 and Month 18 | Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6 | Baseline and Month 6 | Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population. |
| Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18 | Baseline, Month 12 and Month 18 | Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population. |
| Sitting Height-Standard Deviation Score (SDS) | Baseline, Month 6, Month 12 and Month 18 | Sitting height was measured using a stadiometer with a specialized chair. The SDS indicates how similar the participant was to the reference population. |
| Body Mass Index-Standard Deviation Score (BMI-SDS) | Baseline, Month 6, Month 12 and Month 18 | The BMI was used to measure body fat based on height and weight. It was calculated by body weight (kg) divided by the height (m) squared. The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Head Circumference at Months 6, 12 and 18 | Baseline, Month 6, Month 12 and Month 18 | The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion). |
| Change From Baseline in Head Circumference-Standard Deviation Score (SDS) at Months 6, 12 and 18 | Baseline, Month 6, Month 12 and Month 18 | The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion). The SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 | Baseline and Month 6 | Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Months 12 and 18 | Baseline, Month 12 and Month 18 | Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline and Month 6 | K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme \[greater than (\>) 131\], above average (116-130), average (85-115), below average (70-84), lower extreme \[less than (\<) 69\]. |
| Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Months 12 and 18 | Baseline, Month 12 and Month 18 | K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme \[greater than (\>) 131\], above average (116-130), average (85-115), below average (70-84), lower extreme \[less than (\<) 69\]. |
| Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline and Month 6 | The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); Sustained Attention, change of reaction (Flexibility); Divided Attention, controlled reaction disposition (Go/No go) and Vigilance. It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results. |
| Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Months 12 and 18 | Baseline, Month 12 and Month 18 | The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); Sustained Attention, change of reaction (Flexibility); Divided Attention, controlled reaction disposition (Go/No go) and Vigilance. It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results. |
| Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline and Month 6 | NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores\[sum of differences of correct {C} - incorrect {IC} Yes answers(1);sum of C Yes answers(2);sum of IC Yes answers(3);sum of differences of C-IC Yes answers with high associative items{ 87%-95%}(4);sum of differences of C-IC Yes answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)\].Scores were rated as below average(\<40), average(40-60), above average(\>60) and working time ranging between 9-12 minutes. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bone Density Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months | Baseline, Month 6, Month 12 and Month 18 | Bone Mineral Density (BMD) was measured by pqCT. The Z-score measures the distance of the measured BMD value from the appropriate normal age matched population mean value in units of standard deviation of this population. More negative scores indicate less BMD compared to age matched population and more positive scores indicate higher BMD compared to age matched population. |
| Change From Baseline in Bone Stability Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months | Baseline, Month 6, Month 12 and Month 18 | Bone stability was measured by pqCT. Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- (or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average. |
| Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months | Baseline, Month 6, Month 12 and Month 18 | Bone structure was measured by pqCT.Parameters included:total area,cortical area,marrow area,cortical thickness,cortical density of the radius,bone strength,cross-sectional muscle and fat area,total bone density,bone mineral count,trabecular BMD,bone cross-sectional area.Baseline and post-baseline SDS values transformed to age and sex specific z-score(\[Ln(test result/M)\]/S);Ln=natural logarithm;M=age-/height- and sex-specific mean value;S=age-/height- and sex-specific coefficient of variation).Positive values are above the average for participant's age and sex;negative values are below. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Somatropin Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals. | 12 |
| Control Arm No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months. | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Does not meet inclusion criteria | 1 | 0 |
| Overall Study | Randomized but not treated | 0 | 1 |
| Overall Study | Terminated by sponsor | 2 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Somatropin | Control Arm | Total |
|---|---|---|---|
| Age Continuous | 6.6 Years STANDARD_DEVIATION 1 | 7.6 Years STANDARD_DEVIATION 1.4 | 7.1 Years STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 12 | 7 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6
Vmax was measured by Leonardo Jumping Platform during two-leg jump.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | 0.01 Meter/second (m/s) | Standard Error 0.08 |
| Control Arm | Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | 0.12 Meter/second (m/s) | Standard Error 0.09 |
Primary
Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6
Vmax was measured by Leonardo Jumping Platform during two-leg jump.
Time frame: Baseline and Month 6
Population: PP population included participants who received the study medication for at least 22 weeks. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | 0.01 m/s | Standard Error 0.05 |
| Control Arm | Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | 0.25 m/s | Standard Error 0.06 |
Primary
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6
PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | -0.70 Newtons | Standard Error 0.62 |
| Control Arm | Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | -0.55 Newtons | Standard Error 0.29 |
Primary
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6
PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline and Month 6
Population: PP population included participants who received the study medication for at least 22 weeks. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | -0.83 Newtons | Standard Error 1.27 |
| Control Arm | Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | -0.85 Newtons | Standard Error 0.73 |
Primary
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6
Peak jump power (PJP) was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | -0.15 Watt/kilogram (W/kg) | Standard Error 1.01 |
| Control Arm | Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 | 0.28 Watt/kilogram (W/kg) | Standard Error 0.51 |
Comparison: Analysis of covariance (ANCOVA) method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.723295% CI: [-3.93, 3.08]ANCOVA
Primary
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6
PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline and Month 6
Population: PP population included participants who received the study medication for at least 22 weeks. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | -1.02 W/kg | Standard Error 0.43 |
| Control Arm | Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 | 0.59 W/kg | Standard Error 0.27 |
Comparison: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.194195% CI: [-8.04, 4.82]ANCOVA
Secondary
Body Mass Index-Standard Deviation Score (BMI-SDS)
The BMI was used to measure body fat based on height and weight. It was calculated by body weight (kg) divided by the height (m) squared. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 | Change at Month 6 | 0.2 m/s | Standard Deviation 0.29 |
| Somatropin | Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 | Baseline | 0.7 m/s | Standard Deviation 0.22 |
| Control Arm | Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 | Baseline | 0.6 m/s | Standard Deviation 0.16 |
| Control Arm | Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 | Change at Month 6 | 0.0 m/s | Standard Deviation 0.18 |
Secondary
Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Months 12 and 18
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 | Baseline | 0.4 kilonewton (kN) | Standard Deviation 0.11 |
| Somatropin | Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 | Change at Month 6 | -0.0 kilonewton (kN) | Standard Deviation 0.23 |
| Control Arm | Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 | Baseline | 0.4 kilonewton (kN) | Standard Deviation 0.19 |
| Control Arm | Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 | Change at Month 6 | 0.0 kilonewton (kN) | Standard Deviation 0.2 |
Secondary
Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Months 12 and 18
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 | Baseline | 0.1 kilowatt (kW) | Standard Deviation 0.07 |
| Somatropin | Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 | Change at Month 6 | 0.0 kilowatt (kW) | Standard Deviation 0.07 |
| Control Arm | Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 | Baseline | 0.1 kilowatt (kW) | Standard Deviation 0.05 |
| Control Arm | Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 | Change at Month 6 | 0.0 kilowatt (kW) | Standard Deviation 0.05 |
Secondary
Change From Baseline in Five-chair Rising Test-Peak Jump Power (PJP) at Months 12 and 18
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6
Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Baseline (Average rise time) | 1.2 seconds | Standard Deviation 0.9 |
| Somatropin | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Change at Month 6 (Average rise time) | -0.5 seconds | Standard Deviation 1.15 |
| Somatropin | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Baseline (Average time per test) | 2.0 seconds | Standard Deviation 0.7 |
| Somatropin | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Change at Month 6 (Average time per test) | -0.2 seconds | Standard Deviation 0.54 |
| Somatropin | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Baseline (Total time to perform 5 tests) | 9.6 seconds | Standard Deviation 3.91 |
| Somatropin | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Change at Month 6 (Total time to perform 5 tests) | 0.1 seconds | Standard Deviation 3.04 |
| Control Arm | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Baseline (Total time to perform 5 tests) | 10.8 seconds | Standard Deviation 2.24 |
| Control Arm | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Baseline (Average rise time) | 0.7 seconds | Standard Deviation 0.31 |
| Control Arm | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Change at Month 6 (Average time per test) | -0.1 seconds | Standard Deviation 0.87 |
| Control Arm | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Change at Month 6 (Average rise time) | 0.1 seconds | Standard Deviation 0.27 |
| Control Arm | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Change at Month 6 (Total time to perform 5 tests) | 2.0 seconds | Standard Deviation 8.48 |
| Control Arm | Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 | Baseline (Average time per test) | 2.3 seconds | Standard Deviation 0.6 |
Secondary
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Months 12 and 18
Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6
Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6 | 3.89 cm/year | Standard Error 1.02 |
| Control Arm | Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6 | -0.77 cm/year | Standard Error 1.4 |
Comparison: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.016195% CI: [1.13, 8.21]ANCOVA
Secondary
Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18
Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Head Circumference at Months 6, 12 and 18
The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion).
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Head Circumference-Standard Deviation Score (SDS) at Months 6, 12 and 18
The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion). The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6
Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6 | 0.33 cm | Standard Error 0.21 |
| Control Arm | Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6 | -0.22 cm | Standard Error 0.25 |
Comparison: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.110795% CI: [-0.15, 1.25]ANCOVA
Secondary
Change From Baseline in Height-Standard Deviation Score (SDS) at Months 12 and 18
Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Intellectual Performance of Children Using Child Behavior Checklist 4-18 Years (CBCL 4-18) at Months 6, 12 and 18
CBCL was standardized for children ages 4 to 18 years and measured child internalizing and externalizing behaviors and total problems. The 4-18 years' checklist contains 140 questions and responses were recorded on a Likert scale: 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. The range of possible values was 0-280 (0=good to 280=worst).
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6
K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme \[greater than (\>) 131\], above average (116-130), average (85-115), below average (70-84), lower extreme \[less than (\<) 69\].
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Sequential Processing) | 25.7 Units on a scale | Standard Deviation 8.35 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Sequential Processing) | 2.6 Units on a scale | Standard Deviation 5.82 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Simultaneous Processing) | 45.7 Units on a scale | Standard Deviation 7.2 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Simultaneous Processing) | -0.1 Units on a scale | Standard Deviation 4.53 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Achievement) | 300.7 Units on a scale | Standard Deviation 66.83 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Achievement) | 32.1 Units on a scale | Standard Deviation 48.79 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Nonverbal) | 46.2 Units on a scale | Standard Deviation 8.65 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Nonverbal) | -1.4 Units on a scale | Standard Deviation 3.78 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Mental Processing Composite) | 70.0 Units on a scale | Standard Deviation 12.38 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Mental Processing Composite) | 1.4 Units on a scale | Standard Deviation 6.39 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Nonverbal) | 0.0 Units on a scale | Standard Deviation 5.35 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Sequential Processing) | 28.5 Units on a scale | Standard Deviation 8.33 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Achievement) | 16.7 Units on a scale | Standard Deviation 27.52 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Sequential Processing) | -1.9 Units on a scale | Standard Deviation 4.15 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Mental Processing Composite) | -0.9 Units on a scale | Standard Deviation 7.28 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Simultaneous Processing) | 49.8 Units on a scale | Standard Deviation 12.74 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Nonverbal) | 49.8 Units on a scale | Standard Deviation 13.21 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Change at Month 6 (Simultaneous Processing) | 1.5 Units on a scale | Standard Deviation 4.3 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Mental Processing Composite) | 78.1 Units on a scale | Standard Deviation 19.95 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 | Baseline (Achievement) | 341.8 Units on a scale | Standard Deviation 76.88 |
Comparison: For K-ABC Test (Sequential Processing): Kruskal-Wallis Analysis of Variance (ANOVA) model was used to calculate p-value.p-value: 0.0532Kruskal-Wallis
Comparison: For K-ABC Test (Simultaneous Processing): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.3383Kruskal-Wallis
Comparison: For K-ABC Test (Achievement): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.683Kruskal-Wallis
Comparison: For K-ABC Test (Non-Verbal): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.4935Kruskal-Wallis
Comparison: For K-ABC Test (Mental Processing Composite): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.3458Kruskal-Wallis
Secondary
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Months 12 and 18
K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme \[greater than (\>) 131\], above average (116-130), average (85-115), below average (70-84), lower extreme \[less than (\<) 69\].
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6
The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); Sustained Attention, change of reaction (Flexibility); Divided Attention, controlled reaction disposition (Go/No go) and Vigilance. It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure and 'n' signifies participants who received the study drug and evaluated at the time point for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Distractibility) | 554.3 Seconds | Standard Deviation 201.08 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Distractibility) (n= 7, 10) | 5.6 Seconds | Standard Deviation 230.95 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Alertness) | 433.9 Seconds | Standard Deviation 140.74 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Alertness) (n= 8, 10) | -16.1 Seconds | Standard Deviation 80.85 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Flexibility) | 1350.0 Seconds | Standard Deviation 470.5 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Flexibility) (n= 8, 10) | -192.0 Seconds | Standard Deviation 492.73 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Go/No Go) | 539.8 Seconds | Standard Deviation 106.73 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Go/No Go) (n= 8, 9) | 35.6 Seconds | Standard Deviation 113.38 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Vigilance) | 822.2 Seconds | Standard Deviation 200.65 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Vigilance) (n= 7, 10) | -146.0 Seconds | Standard Deviation 278.6 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Go/No Go) (n= 8, 9) | -50.2 Seconds | Standard Deviation 69.9 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Distractibility) | 514.5 Seconds | Standard Deviation 127.41 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Flexibility) (n= 8, 10) | -211.0 Seconds | Standard Deviation 589.41 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Distractibility) (n= 7, 10) | -11.4 Seconds | Standard Deviation 139.52 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Vigilance) (n= 7, 10) | -31.2 Seconds | Standard Deviation 107.62 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Alertness) | 384.6 Seconds | Standard Deviation 124.94 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Go/No Go) | 514.9 Seconds | Standard Deviation 91.95 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Change at 6 Month (Alertness) (n= 8, 10) | 4.0 Seconds | Standard Deviation 107.42 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Vigilance) | 693.4 Seconds | Standard Deviation 118.01 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 | Baseline (Flexibility) | 1313.0 Seconds | Standard Deviation 477.19 |
Comparison: For KITAP Test (Distractibility): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.6256Kruskal-Wallis
Comparison: For KITAP Test (Alertness): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.859Kruskal-Wallis
Comparison: For KITAP Test (Flexibility): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 1Kruskal-Wallis
Comparison: For KITAP Test (Go/No Go): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.1234Kruskal-Wallis
Comparison: For KITAP Test (Vigilance): Kruskal-Wallis ANOVA model was used to calculate p-value.p-value: 0.3291Kruskal-Wallis
Secondary
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Months 12 and 18
The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); Sustained Attention, change of reaction (Flexibility); Divided Attention, controlled reaction disposition (Go/No go) and Vigilance. It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6
NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores\[sum of differences of correct {C} - incorrect {IC} Yes answers(1);sum of C Yes answers(2);sum of IC Yes answers(3);sum of differences of C-IC Yes answers with high associative items{ 87%-95%}(4);sum of differences of C-IC Yes answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)\].Scores were rated as below average(\<40), average(40-60), above average(\>60) and working time ranging between 9-12 minutes.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (6)] | 44.9 Units on a scale | Standard Deviation 15.83 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (1)] | 39.9 Units on a scale | Standard Deviation 13.6 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (6)] | 0.9 Units on a scale | Standard Deviation 16.55 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (3)] | 45.9 Units on a scale | Standard Deviation 14.89 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (1)] | 33.4 Units on a scale | Standard Deviation 12.18 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 (Instability Index) | -0.1 Units on a scale | Standard Deviation 0.11 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (1)] | 6.0 Units on a scale | Standard Deviation 10.21 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (3)] | 1.5 Units on a scale | Standard Deviation 5.15 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (2)] | 51.3 Units on a scale | Standard Deviation 7.55 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (1)] | 4.4 Units on a scale | Standard Deviation 11.64 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (2)] | 3.1 Units on a scale | Standard Deviation 5.59 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (4)] | 39.3 Units on a scale | Standard Deviation 16.97 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (3)] | 40.0 Units on a scale | Standard Deviation 13.86 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 (Working Time) | 10.6 Units on a scale | Standard Deviation 92.95 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (3)] | 0.6 Units on a scale | Standard Deviation 4.47 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (4)] | 5.6 Units on a scale | Standard Deviation 15.53 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (4)] | 37.4 Units on a scale | Standard Deviation 17.01 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (2)] | 41.6 Units on a scale | Standard Deviation 12.97 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (4)] | 6.3 Units on a scale | Standard Deviation 14.57 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (5)] | 43.3 Units on a scale | Standard Deviation 11.12 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (5)] | 35.0 Units on a scale | Standard Deviation 11.88 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline (Working Time) | 227.0 Units on a scale | Standard Deviation 44.27 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (5)] | 3.3 Units on a scale | Standard Deviation 10.73 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (5)] | 2.6 Units on a scale | Standard Deviation 9.83 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (6)] | 50.0 Units on a scale | Standard Deviation 16.49 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (2)] | 5.0 Units on a scale | Standard Deviation 10.72 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (6)] | 1.5 Units on a scale | Standard Deviation 19.06 |
| Somatropin | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline (Instability Index) | 0.3 Units on a scale | Standard Deviation 0.15 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (6)] | -4.1 Units on a scale | Standard Deviation 13.77 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline (Instability Index) | 0.2 Units on a scale | Standard Deviation 0.21 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 (Instability Index) | -0.1 Units on a scale | Standard Deviation 0.2 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline (Working Time) | 218.3 Units on a scale | Standard Deviation 76.89 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 (Working Time) | -11.1 Units on a scale | Standard Deviation 34.86 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (1)] | 43.9 Units on a scale | Standard Deviation 16.53 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (1)] | 6.7 Units on a scale | Standard Deviation 12.12 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (2)] | 46.8 Units on a scale | Standard Deviation 14.4 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (2)] | -0.6 Units on a scale | Standard Deviation 5.5 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (3)] | 48.1 Units on a scale | Standard Deviation 18.2 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (3)] | 8.3 Units on a scale | Standard Deviation 12.24 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (4)] | 46.4 Units on a scale | Standard Deviation 16.03 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (4)] | 1.4 Units on a scale | Standard Deviation 11.75 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (5)] | 43.6 Units on a scale | Standard Deviation 15.13 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (5)] | 7.7 Units on a scale | Standard Deviation 12.59 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [T-scores (6)] | 52.9 Units on a scale | Standard Deviation 19.96 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [T-scores (6)] | -7.4 Units on a scale | Standard Deviation 14.88 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (1)] | 38.6 Units on a scale | Standard Deviation 13.43 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (1)] | 5.2 Units on a scale | Standard Deviation 11.26 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (2)] | 54.5 Units on a scale | Standard Deviation 8.1 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (2)] | -0.1 Units on a scale | Standard Deviation 3.38 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (3)] | 41.1 Units on a scale | Standard Deviation 16.38 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (3)] | 7.8 Units on a scale | Standard Deviation 12.13 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (4)] | 45.0 Units on a scale | Standard Deviation 15.21 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (4)] | 4.1 Units on a scale | Standard Deviation 10.63 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (5)] | 37.3 Units on a scale | Standard Deviation 13.48 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Change at Month 6 [Age-corrected T-scores (5)] | 6.9 Units on a scale | Standard Deviation 12.57 |
| Control Arm | Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 | Baseline [Age-corrected T-scores (6)] | 55.5 Units on a scale | Standard Deviation 16.64 |
Secondary
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Months 12 and 18
NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores\[sum of differences of correct {C} - incorrect {IC} Yes answers(1);sum of C Yes answers(2);sum of IC Yes answers(3);sum of differences of C-IC Yes answers with high associative items{ 87%-95%}(4);sum of differences of C-IC Yes answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)\].Scores were rated as below average(\<40), average(40-60), above average(\>60) and working time ranging between 9-12 minutes.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6
MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6 | 1.28 kg | Standard Error 1.69 |
| Control Arm | Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6 | 1.13 kg | Standard Error 1.64 |
Comparison: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.95695% CI: [-5.71, 6]ANCOVA
Secondary
Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Months 12 and 18
MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Maximum Jump Velocity (Vmax; One-leg-jump) at Months 6, 12 and 18
Vmax was measured by Leonardo Jumping Platform during one leg jump.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in One-chair Rising Test-Peak Jump Force (PJF) at Months 6, 12 and 18
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Time frame: Baseline, Month 6 , Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in One-chair Rising Test-Peak Jump Power (PJP) at Months 6, 12 and 18
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Time frame: Baseline, Month 6 , Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in One-chair Rising Test (Time to Perform the Tasks) at Months 6, 12 and 18
The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising).
Time frame: Baseline, Month 6 , Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; One-leg-jump) at Months 6, 12 and 18
PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during one leg jump. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; One-leg-jump) at Months 6, 12 and 18
PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during one leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 6 , Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6
Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.
Time frame: Baseline and Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 | Change at Month 6 (Triceps SDS) | -0.41 Millimeter (mm) | Standard Error 0.16 |
| Somatropin | Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 | Change at Month 6 (Subscapular SDS) | -0.30 Millimeter (mm) | Standard Error 0.1 |
| Somatropin | Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 | Change at Month 6 (Suprailiac SDS) | -0.60 Millimeter (mm) | Standard Error 0.07 |
| Control Arm | Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 | Change at Month 6 (Triceps SDS) | -0.06 Millimeter (mm) | Standard Error 0.18 |
| Control Arm | Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 | Change at Month 6 (Subscapular SDS) | -0.16 Millimeter (mm) | Standard Error 0.13 |
| Control Arm | Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 | Change at Month 6 (Suprailiac SDS) | -0.33 Millimeter (mm) | Standard Error 0.12 |
Comparison: Subscapular SDS: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.349495% CI: [-0.49, 0.19]ANCOVA
Comparison: Triceps SDS: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.18795% CI: [-0.89, 0.2]ANCOVA
Comparison: Suprailiac SDS: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.p-value: 0.045895% CI: [-0.54, -0.01]ANCOVA
Secondary
Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Months 12 and 18
Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Mean Calf Circumference
Calf measurements were taken as a mean of 3 consecutive measurements at largest part of calf muscle, usually about 4 inches down from below the knee.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Mean Growth Velocity at Month 6
Growth velocity measures the annual rate of increase in height.
Time frame: Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Mean Growth Velocity at Month 6 | 8.2 cm/year | Standard Deviation 1.93 |
| Control Arm | Mean Growth Velocity at Month 6 | 4.6 cm/year | Standard Deviation 1.44 |
Secondary
Mean Growth Velocity at Months 12 and 18
Growth velocity measures the annual rate of increase in height.
Time frame: Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6
Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Time frame: Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6 | 3.4 cm/year | Standard Deviation 2.62 |
| Control Arm | Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6 | -1.1 cm/year | Standard Deviation 1.43 |
Secondary
Mean Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18
Time frame: Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Mean Height at Month 6
Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.
Time frame: Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Mean Height at Month 6 | 112.8 cm | Standard Deviation 5.13 |
| Control Arm | Mean Height at Month 6 | 115.0 cm | Standard Deviation 7.93 |
Secondary
Mean Height at Months 12 and 18
Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.
Time frame: Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Mean Height-Standard Deviation Score (SDS) at Month 6
Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time frame: Month 6
Population: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin | Mean Height-Standard Deviation Score (SDS) at Month 6 | -3.1 cm | Standard Deviation 0.86 |
| Control Arm | Mean Height-Standard Deviation Score (SDS) at Month 6 | -3.7 cm | Standard Deviation 0.77 |
Secondary
Mean Height-Standard Deviation Score (SDS) at Months 12 and 18
Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time frame: Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Mean Thigh Circumference
Thigh measurements were taken as a mean of 3 consecutive measurements at upper thigh about an inch down from the crotch line.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Mean Upper Arm Circumference
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Secondary
Sitting Height-Standard Deviation Score (SDS)
Sitting height was measured using a stadiometer with a specialized chair. The SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Other Pre-specified
Change From Baseline in Bone Density Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
Bone Mineral Density (BMD) was measured by pqCT. The Z-score measures the distance of the measured BMD value from the appropriate normal age matched population mean value in units of standard deviation of this population. More negative scores indicate less BMD compared to age matched population and more positive scores indicate higher BMD compared to age matched population.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Other Pre-specified
Change From Baseline in Bone Stability Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
Bone stability was measured by pqCT. Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- (or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.
Other Pre-specified
Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
Bone structure was measured by pqCT.Parameters included:total area,cortical area,marrow area,cortical thickness,cortical density of the radius,bone strength,cross-sectional muscle and fat area,total bone density,bone mineral count,trabecular BMD,bone cross-sectional area.Baseline and post-baseline SDS values transformed to age and sex specific z-score(\[Ln(test result/M)\]/S);Ln=natural logarithm;M=age-/height- and sex-specific mean value;S=age-/height- and sex-specific coefficient of variation).Positive values are above the average for participant's age and sex;negative values are below.
Time frame: Baseline, Month 6, Month 12 and Month 18
Population: Data were not analyzed as study was prematurely terminated due to insufficient number of participants.