Growth Disorder, Idiopathic Short Stature
Conditions
Brief summary
This trial is conducted in Asia. The aim of this trial is to evaluate the efficacy and safety of recombinant human growth hormone (hGH) in subjects with idiopathic short stature in Korea.
Interventions
DRUGsomatropin
A weekly dosage of 0.469 mg of somatropin per kg of body weight per week will be injected subcutaneously (under the skin) in the evening in 7 days per week.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained from subject's parents or legally acceptable representative before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) * Pre-pubertal status (males aged from 4 to 11 \[both inclusive\], females aged from 4 to 9 \[both inclusive\]): an absence of breast development in females (Tanner 1 only) and testicular volume below 4 mL in males * Growth hormone level above 10 ng/mL following a stimulation test (test result within 6 months from screening can be used) * Height below 3 percentile * Bone age below or equal to 12 year * Epiphyses confirmed as open in patients at least 10 years or more of age
Exclusion criteria
* Known presence of one or more pituitary hormone deficiencies (ACTH (adrenocorticotropic hormone), ADH (antidiuretic hormone), FSH (follicle-stimulating hormone), LH (luteinising hormone), TSH (thyroid-stimulating hormone)) * Known primary hypothyroidism, adrenal insufficiency or hypogonadism (treated or untreated) * Specific types of growth failure including, but not limited to, known chromosomal abnormalities associated with growth failure and altered sensitivity to growth hormone * Bone age is advanced over chronological age more than 3 years * Active malignancy, CNS (central nervous system) trauma, active chemotherapy or radiation therapy for neoplasia * Prior history of intracranial hypertension * Hypertrophic cardiomyopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Height Velocity (Ht-V) | After 6 months of treatment | Height velocity (Ht-V) (cm/year) is the change in height per year (after 6 months of treatment). Ht-V was calculated by Novo Nordisk. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in IGF Related Factors: IGF-I (Insulin-like Growth Factor-I) | After 6 months of treatment. | IGF-I (insulin-like growth factor-1) was measured at Visit 1 (screening),Visit 3 (3 months ± 7 days ),Visit 4 (6 months ± 7 days),Visit 5 (9 months ± 7 days ) and Visit 6 (12 months ± 7 days ). Change of IGF-I from baseline to 6 months treatment was calculated. |
| Change in IGF Related Factors: IGFBP-3 (Insulin-like Growth Factor Binding Protein-3) | After 6 months of treatment. | IGFBP-3 was measured at Visit 1(screening), Visit 3 (3 months ± 7 days ), Visit 4 (6 months ± 7 days), 5 (9 months ± 7 days ) and 6 ( 12 months ± 7 days). Change of IGFBP-3 from baseline to 6 months treatment were calculated. |
| Change in Ht-SDS (Height Standard Deviation Score) | After 6 months of treatment. | Height standard deviation scores (HSDS) were calculated using Korean growth data (reported by the Korea Centre for Disease Control and Prevention). The mean normal range for HSDS is from -2 to +2. Negative scores below -2 indicate a height below normal range, whereas positive scores above +2 indicate a height above normal. |
| Occurrence of Adverse Events | Throughout the trial (12 months) | AEs were collected throughout the trial in both groups. |
| Ht-V (Height Velocity) | At the first 6 months and the last 6 months in group A | Height velocity (Ht-V) (cm/year) is the change in height per year (after 6 months of treatment). Three sort of Ht-V was calculated from height data at Visit 2 (day 0), 4 (6 months ± 7 days) and 6 (12 months ± 7 days), as follows: Between Visits 2 and 4, between Visit 4 and 6 and between Visit 2 and 6. Ht-V was calculated by Novo Nordisk. It is the difference between Ht-V for the last 6 months and Ht-V for the first 6 months of treatment. This endpoint was only evaluated for Group A as per the trial protocol. |
| Change in Bone Age | After 6 months of treatment. | Change in bone age from the baseline to 6 months. |
Countries
South Korea
Participant flow
Recruitment details
The trial was conducted at 10 sites in Korea.
Participants by arm
| Arm | Count |
|---|---|
| Group A: 12-month GH Treatment For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®. | 36 |
| Group B: 6-month Untreated + 6-month GH Treatment Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®. | 15 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Group A: 12-month GH Treatment | Group B: 6-month Untreated + 6-month GH Treatment | Total |
|---|---|---|---|
| Age, Continuous | 6.3 years STANDARD_DEVIATION 1.5 | 5.9 years STANDARD_DEVIATION 1.2 | 6.2 years STANDARD_DEVIATION 1.5 |
| Height | 107.7 cm STANDARD_DEVIATION 8.7 | 105.8 cm STANDARD_DEVIATION 7.5 | 107.1 cm STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 17 Participants | 6 Participants | 23 Participants |
| Sex: Female, Male Male | 19 Participants | 9 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 36 | 10 / 15 |
| serious Total, serious adverse events | 4 / 36 | 2 / 15 |
Outcome results
Primary
Height Velocity (Ht-V)
Height velocity (Ht-V) (cm/year) is the change in height per year (after 6 months of treatment). Ht-V was calculated by Novo Nordisk.
Time frame: After 6 months of treatment
Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B. Four (4) subjects had missing height at baseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: 12-month GH Treatment | Height Velocity (Ht-V) | 12.02 cm/year | Standard Error 0.29 |
| Group B: 6-month Untreated + 6-month GH Treatment | Height Velocity (Ht-V) | 6.87 cm/year | Standard Error 0.43 |
Comparison: Let D be a mean difference of the primary endpoint between group A and group B. Null hypothesis H0: D = 0 vs. alternative H1: D ≠ 0 will be statistically tested by an ANOVA model.p-value: <0.000195% CI: [4.09, 6.21]ANOVA
Secondary
Change in Bone Age
Change in bone age from the baseline to 6 months.
Time frame: After 6 months of treatment.
Population: Safety analysis set (SAS) :includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: 12-month GH Treatment | Change in Bone Age | 0.5 years | Standard Deviation 0.2 |
| Group B: 6-month Untreated + 6-month GH Treatment | Change in Bone Age | 0.5 years | Standard Deviation 0.2 |
Secondary
Change in Ht-SDS (Height Standard Deviation Score)
Height standard deviation scores (HSDS) were calculated using Korean growth data (reported by the Korea Centre for Disease Control and Prevention). The mean normal range for HSDS is from -2 to +2. Negative scores below -2 indicate a height below normal range, whereas positive scores above +2 indicate a height above normal.
Time frame: After 6 months of treatment.
Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B. Four (4) subjects had missing height at baseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: 12-month GH Treatment | Change in Ht-SDS (Height Standard Deviation Score) | 0.76 Standard Deviation Score (SDS) | Standard Error 0.04 |
| Group B: 6-month Untreated + 6-month GH Treatment | Change in Ht-SDS (Height Standard Deviation Score) | 0.19 Standard Deviation Score (SDS) | Standard Error 0.06 |
Secondary
Change in IGF Related Factors: IGFBP-3 (Insulin-like Growth Factor Binding Protein-3)
IGFBP-3 was measured at Visit 1(screening), Visit 3 (3 months ± 7 days ), Visit 4 (6 months ± 7 days), 5 (9 months ± 7 days ) and 6 ( 12 months ± 7 days). Change of IGFBP-3 from baseline to 6 months treatment were calculated.
Time frame: After 6 months of treatment.
Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: 12-month GH Treatment | Change in IGF Related Factors: IGFBP-3 (Insulin-like Growth Factor Binding Protein-3) | 0.89 mcg/mL | Standard Error 0.19 |
| Group B: 6-month Untreated + 6-month GH Treatment | Change in IGF Related Factors: IGFBP-3 (Insulin-like Growth Factor Binding Protein-3) | 0.22 mcg/mL | Standard Error 0.3 |
Secondary
Change in IGF Related Factors: IGF-I (Insulin-like Growth Factor-I)
IGF-I (insulin-like growth factor-1) was measured at Visit 1 (screening),Visit 3 (3 months ± 7 days ),Visit 4 (6 months ± 7 days),Visit 5 (9 months ± 7 days ) and Visit 6 (12 months ± 7 days ). Change of IGF-I from baseline to 6 months treatment was calculated.
Time frame: After 6 months of treatment.
Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: 12-month GH Treatment | Change in IGF Related Factors: IGF-I (Insulin-like Growth Factor-I) | 192.58 ng/ml | Standard Error 14 |
| Group B: 6-month Untreated + 6-month GH Treatment | Change in IGF Related Factors: IGF-I (Insulin-like Growth Factor-I) | 28.03 ng/ml | Standard Error 21.81 |
Secondary
Ht-V (Height Velocity)
Height velocity (Ht-V) (cm/year) is the change in height per year (after 6 months of treatment). Three sort of Ht-V was calculated from height data at Visit 2 (day 0), 4 (6 months ± 7 days) and 6 (12 months ± 7 days), as follows: Between Visits 2 and 4, between Visit 4 and 6 and between Visit 2 and 6. Ht-V was calculated by Novo Nordisk. It is the difference between Ht-V for the last 6 months and Ht-V for the first 6 months of treatment. This endpoint was only evaluated for Group A as per the trial protocol.
Time frame: At the first 6 months and the last 6 months in group A
Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Group A: 12-month GH Treatment | Ht-V (Height Velocity) | 2.80 cm/year |
Secondary
Occurrence of Adverse Events
AEs were collected throughout the trial in both groups.
Time frame: Throughout the trial (12 months)
Population: Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: 12-month GH Treatment | Occurrence of Adverse Events | 70 events |
| Group B: 6-month Untreated + 6-month GH Treatment | Occurrence of Adverse Events | 25 events |