Somatropin + Leuprorelin vs Somatropin Alone in Pubertal Children With Idiopathic Short Stature

Study Overview
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Brief Summary
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The present randomized trial was initially intended to study the benefits of a combined treatment with growth hormone (GH) and a gonadotropin-releasing hormone (GnRH) agonist for pubertal children with idiopathic short stature. However, treatments were stopped in January 2012 at the request of the French drug agency. Therefore, a protocol amendment divided the study in two study periods. Study Period 1 involved combined treatment with somatropin and leuprorelin or treatment with somatropin alone. Participants from France who participated in this Period 1 of the study were asked to participate in a long term safety follow up defined as a Period 2 of the study. Participants from the Netherlands were offered participation in Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS, clinicaltrials.gov Identifier: NCT01088412) for long term safety follow up independent of this study.

Official Title
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Efficacy and Safety of Somatropin in Combination With Leuprorelin Compared to Somatropin Alone in Pubertal Children With Idiopathic Short Stature

Conditions
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Idiopathic Short Stature (ISS)

Intervention / Treatment
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* Drug: somatropin
* Drug: leuprorelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female children with ISS age greater than or equal to 8 years and less than or equal to 12 years and 3 months for girls and greater than or equal to 9 years and less than or equal to 14 years and 3 months for boys bone age less than or equal to 12.0 years for girls and less than or equal to 14.0 years for boys based on a central reading of an X-ray of the left hand and wrist Pubertal stage B2 and B3 for girls based on the Tanner method Pubertal stage G2 and G3 for boys based on the Tanner method Exclusion Criteria: Growth hormone deficiency (GHD) Insulin-like growth factor-I levels greater than 3 SDS Chromosomal abnormality diagnosed locally on a karyotype. For girls, the karyotype to eliminate a Turner syndrome, is mandatory Small for gestational age (SGA) Has reached menarche (had her first menstrual period) Have any significant concomitant disease that is likely to interfere with growth or with the study, or is a known contraindication to Growth Hormone treatment

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 171 Months

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: 1<br> | Drug: somatropin<br>* 0.05 mg/kg/day<br>* Other names: Humatrope;Drug: leuprorelin<br>* 11.25 mg/3 months<br>|
| Experimental: 2<br> | Drug: somatropin<br>* 0.05 mg/kg/day<br>* Other names: Humatrope;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Drug-related Adverse Events | A drug-related AE was an AE that occurred postdose or was present predose and became more severe postdose and was considered to be related to study treatment. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. | Baseline through End of Study (up to 9 years) | 
| Adult Height Standard Deviation Score (SDS) | The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. | Baseline through End of Study (up to 9 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity | Height velocity is the difference between 2 height measurements, divided by years elapsed between measurements. | Baseline through End of Study (up to 9 years) | 
| Height SDS | SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. | Baseline through End of Study (up to 9 years) | 
| Difference Between Adult Height SDS and Target Height SDS | This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of target height [calculated as (mother's height (SDS) + father's height (SDS))/2] for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. | Baseline through End of Study (up to 9 years) | 
| Difference Between Adult Height SDS and Baseline Predicted Height SDS | This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of baseline predicted height [calculated using the Bayley-Pinneau method based on height and bone age] for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. | Baseline through End up Study (up to 9 years) | 
| Difference Between Adult Height SDS and Baseline Height SDS | This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of baseline height for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. | Baseline through End up Study (up to 9 years) | 
| Percentage of Children With Normal Adult Height SDS | Percentage of children with normal adult height SDS (greater than -2 SDS and less than +2 SDS) | Baseline through End of Study (up to 9 years) | 
| Bone Age | Bone age measured using the X-Ray of left hand and wrist. | Baseline through End of Study (up to 9 years) |