Growth Hormone Treatment for the Prevention of Short Stature in Young Girls With Turner Syndrome Before the Age of 4 Years

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy and safety of recombinant human growth hormone (r-hGH) treatment in girls with Turner Syndrome under the age of 4 years. After 4 years of treatment, height in these girls will be compared with an historical control group of untreated girls with Turner Syndrome, matched for age and height at baseline.

Official Title
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Collaborative Study to Assess the Effects of Treatment With Recombinant Growth Hormone Saizen® in the Prevention of Short Stature in Young Girls Suffering From Turner Syndrome Before the Age of 4 Years. Original French Title: Etude Collaborative Pour apprécier Les Effets du Traitement Par l'Hormone de Croissance Recombinante SAIZEN® Dans le Retard de Croissance de la Fillette Atteinte de Syndrome de Turner Avant l'âge de 4 Ans

Conditions
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Turner's Syndrome

Intervention / Treatment
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* Drug: r-hGH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Young girls with turner syndrome proved by karyotype Growth hormone secretion confirmed with ornithin stimulation test Normal glucidic metabolism confirmed by assessment of HbA1c None associated severe pathology which could have impact on growth (i.e. renal insufficiency, decompensated heart failure) No previous or associated treatment with anabolic or sexual steroids Known parental height Exclusion Criteria: Severe associated pathology with impact on growth Concomitant treatment with impact on growth Previous or associated treatment with anabolic steroids Associated growth hormone deficiency

Ages Eligible for Study
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Maximum Age: 4 Years

Sexes Eligible for Study
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Female

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: r-hGH<br>Participants (girls) will receive r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received will depend on participants' baseline height standard deviation score (SDS) relative to the general population standard: participants with a height SDS of -2 standard deviation (SD) or lower will receive 0.05 milligrams per kilogram (mg/kg) per day r-hGH and those with a height SDS between -1 and -2 SD will receive 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants will receive a fixed dose of 0.05 mg/kg per day for a further 2 years. | Drug: r-hGH<br>* Subcutaneous administration.<br>* Other names: Saizen®;|
| No Intervention: Historical Control<br>This arm will include matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height SDS at Year 4 | Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender. | Year 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Abnormal Glycated Hemoglobin (HbA1c) Levels | HbA1c develops when hemoglobin, a protein within red blood cells that carries oxygen throughout the body, joins with glucose in the blood, becoming glycated. The higher the level of glucose in the blood, the higher the level of HbA1c is detectable on red blood cells. The normal range for HbA1c is 4 percent (%) to 5.9%. Number of participants, who had abnormal HbA1c levels any time during the assessment, were reported. | Baseline up to Year 2 | 
| Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) | BA was determined using left wrist and hand X-ray. CA was determined using the date of birth. Difference of BA and CA (BA-CA) was reported. | Baseline, Year 1, Year 2 | 
| Number of Participants With Anti r-hGH Antibodies |  | Baseline up to Year 2 | 
| Number of Participants With Abnormal Insulin-Like Growth Factor 1 (IGF1) Levels | The normal range for IGF1 levels is 45 to 117 nanogram per milliliter (ng/mL) for girls aged less than (<) 3 years and 80 to 236 ng/mL for girls aged 3 to 6 years. Values outside the normal range were considered abnormal. Number of participants, who had abnormal IGF1 levels any time during the assessment, were reported. | Baseline up to Year 2 | 
| Number of Participants Who Reached Normal Height at Year 4 | Participants with normal height were those who attained a height which was within +/- 2 height SDS of reference population standard. Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender. | Year 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth hormone, Turner syndrome, r-hGH, early treatment