Efficacy and Safety of Recombinant Human Growth Hormone on Height Velocity in Subjects With Idiopathic Short Stature

Study Overview
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Brief Summary
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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.

Official Title
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A 12-month, Open-labelled, Randomised, Parallel-group, Multi-centre, Interventional Trial to Evaluate the Efficacy and Safety of Recombinant Human Growth Hormone (hGH) (Norditropin® Nordilet®) Therapy on Height Velocity (Ht-V) in Patients With Idiopathic Short Stature in Korea

Conditions
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Growth Disorder, Idiopathic Short Stature

Intervention / Treatment
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* Drug: somatropin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hGH:12months treatment<br> | Drug: somatropin<br>* 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.<br>|
| Active Comparator: hGH: 6 month un-treatment + 6 month treatment<br> | Drug: somatropin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | After 6 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | After 6 months of treatment. | 
| 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. | After 6 months of treatment. | 
| 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. | After 6 months of treatment. | 
| Change in Bone Age | Change in bone age from the baseline to 6 months. | After 6 months of treatment. | 
| Occurrence of Adverse Events | AEs were collected throughout the trial in both groups. | Throughout the trial (12 months) | 
| 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. | At the first 6 months and the last 6 months in group A |