Predictive Markers in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) Children Treated With SAIZEN®

Study Overview
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Brief Summary
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The study aims at identifying the predictive markers after one month of Saizen therapy in Growth Hormone Deficiency (GHD) and Turner Syndrome children.

Official Title
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A Phase IV Open-label Study of Predictive Markers in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children Treated With SAIZEN®

Conditions
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Growth Hormone Deficiency, Turner Syndrome

Intervention / Treatment
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* Drug: Saizen
* Drug: Saizen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One of the following diagnoses and candidacy for SAIZEN® therapy: A) GHD: documented pre-established diagnosis of GHD with a growth hormone (GH) peak response of <10 microgram per liter (mcg/L) with 2 GH stimulation tests, without priming with oestradiol. B) Turner syndrome: documented pre-established diagnosis by karyotype. Prepubertal status according to Tanner Pre-established history of normal thyroid function or adequate substitution for at least 3 months. Weight for stature within the population specific normal range (>5th and <95th percentiles) for gender Willingness and ability to comply with the protocol for the duration of the study. Parent's or guardian's written informed consent, given before any study related procedure that is not part of the subject's normal medical care, with the understanding that the subject or parent/guardian may withdraw consent at any time without prejudice to future medical care. If the child is old enough to read and write, a separate assent form will be given. Exclusion Criteria: Acquired GHD due to central nervous system tumour, trauma, infection, infiltration (documented by imaging), and history of irradiation or cranial surgery Previous treatment with GH, growth hormone-releasing hormone (GHRH), anabolic steroids or any treatment affecting growth. Previous treatment with corticosteroids, except in case of topical or inhaled corticosteroid administration for atopic disease. Corticosteroids for hormonal substitution are also allowed if the condition and the treatment regimen have been stable for at least 3 months. Severe associated pathology affecting growth such as malnutrition, malabsorption, or bone dysplasia. Chronic severe kidney disease. Chronic severe liver disease. Chronic infectious disease. Acute or severe illness during the previous 6 months. Significant concomitant illness that would interfere with participation or assessment in this study. Active malignancy (except non-melanomatous skin malignancies that have undergone surgical excision and/or biopsy, diagnosis and treatment to resolution) History or active Idiopathic intra-cranial hypertension (benign intracranial hypertension or pseudo-tumor cerebri). Diabetes Mellitus type I & II. Any autoimmune disease. Previous screening failure in this study. Use of an investigational drug or participation in another clinical study within the last three months.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Turner Syndrome (TS)<br> | Drug: Saizen<br>* Subjects with TS will receive SAIZEN® as subcutaneous injection at a dose of 0.050 milligram per kilogram (mg/kg) of body weight per day (within the recommended dosage 0.045-0.050 mg/kg body weight) for a period of 1 month<br>|
| Experimental: Growth Hormone Deficiency (GHD)<br> | Drug: Saizen<br>* Subjects with GHD will receive SAIZEN® as subcutaneous injection at a dose of 0.035 mg/kg of body weight per day (within the recommended dosage 0.025-0.035 mg/kg body weight) for a period of 1 month.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1 | IGF-1 SDS was calculated using the Elmlinger reference method. Change in within subject IGF-1 levels (standard deviation scores) at Month 1 from Baseline was assessed. Descriptive statistics were determined for the Baseline and Month 1 assessments, and also for the level of change between these two assessments. If either the Baseline or Month 1 IGF-1 level was missing, then the within-subject change in IGF-1 was assumed to be missing. | Baseline, Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1 |  | Baseline, Month 1 | 
| Change From Baseline in Fasting Glucose Levels at Month 1 |  | Baseline, Month 1 | 
| Change From Baseline in Fasting Insulin Levels at Month 1 |  | Baseline, Month 1 | 
| Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1 | HOMA-IR is used to assess insulin resistance and calculated by an empirical mathematical formula based on fasting plasma glucose and fasting plasma insulin levels. HOMA-IR = fasting plasma insulin (picomole/liter [pmol/L]) * fasting plasma glucose (millimole/liter [mmol/L]) divided by 22.5. | Baseline, Month 1 | 
| Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1 |  | Baseline, Month 1 |