Safety and Efficacy of Y-shape Pegylated Somatropin in Growth Hormone Deficiency Children

Study Overview
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Brief Summary
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This is a multicenter, randomized, open-labeled, positive controlled phase 2&3 combined study to evaluate the safety and efficacy of weekly Y-shape pegylated somatropin, compared to daily somatropin (Norditropin®), in prepubertal, treatment-naive children with growth hormone deficiency.

Detailed Description
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This multicenter, randomized, open-labeled, positive controlled study is divided into two stages. The first one is aimed to exploit the optimal dose of Y-shape pegylated somatropin, while the second one is aimed to confirm the efficacy and safety of the study drug. A total of 400 prepubertal children with growth hormone deficiency were expected to enrolled. Subjects will firstly undergo a 52 weeks treatment, and then followed for 5 weeks.

Official Title
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A Multi-center, Randomized, Positive-control, Phase 2&3 Combined Study of Y-shape Pegylated Somatropin in Prepubertal Children With Growth Hormone Deficiency.

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Y-shape pegylated somatropin
* Drug: Y-shape pegylated somatropin
* Drug: Y-shape pegylated somatropin
* Drug: Norditropin®
* Drug: Y-shape pegylated somatropin
* Drug: Norditropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of GHD confirmed by two different GH stimulation tests, defined as a peak of GH level of <10.0 ng/ml, determined with a validated assay. Bone age (BA) at least 2 years less than the chronological age. Growth velocity less than 5.0 cm/year. Impaired HT defined as at least 2.0 standard deviations (SD) below of the mean height for chronological age and sex (HT SDS<-2.0). Prepubertal (Tanner Ⅰ) males and females by physical examination, aged older than 3 years and younger than10 years for girls and 11 years for boys. Short stature with normal intelligence. Baseline IGF-1 level below the median IGF-1 level standardized for age and sex. Written, signed informed consent of the parent(s) or legal guardian(s) of the subject and written assent of the subject (if the subject is 8 years old or above). Exclusion Criteria: Prior exposure to growth promotion treatment, such as recombinant human growth hormone or gonadal hormones, for more than 1 month. Known hypersensitivity to somatropin or excipients, such as mannitol, lysine, sodium chloride. Children with closed epiphyses. Short stature etiologies other than GHD, such as idiopathic short stature, Turner syndrome, Prader-Willi syndrome, Russell-Silver syndrome, born small for gestational age regardless of GH status. Other causes of short stature such as hypothyroidism, adrenocortical hormone deficiency, antidiuretic hormone deficiency. Any medical conditions and/or presence that may affect growth velocity such as liver dysfunction, kidney dysfunction, malnutrition, diabetes mellitus, severe dysfunction in major organ such as heart, sever systemic infections, severe immune dysfunction, mental disorders, and other congenital malformations. Suffering from chronic infectious diseases such as chronic hepatitis B, AIDS or tuberculosis. Receiving non-physiological adrenal corticosteroids. Confirmed pituitary and/or hypothalamic malignance by MRI within one year prior to screening. History or presence of any other malignance disease, any evidence of present tumor growth. Evidence of congenital intracranial hypertension. Evidence of slipped capital femoral epiphysis. Evidence of scoliosis over 15°. Participation in any other trial of an investigational agent within 3 months prior to screening. Any other conditions which in the opinion of the investigator precluded enrollment into the study.

Ages Eligible for Study
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Minimum Age: 3 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: Y-shape pegylated somatropin low dose<br> | Drug: Y-shape pegylated somatropin<br>* Y-shape pegylated somatropin 100μg/kg, subcutaneous injection, Once weekly.<br>|
| Experimental: Y-shape pegylated somatropin middle dose<br> | Drug: Y-shape pegylated somatropin<br>* Y-shape pegylated somatropin 120μg/kg, subcutaneous injection, Once weekly.<br>|
| Experimental: Y-shape pegylated somatropin high dose<br> | Drug: Y-shape pegylated somatropin<br>* Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.<br>|
| Active Comparator: Norditropin-1<br> | Drug: Norditropin®<br>* Norditropin 245μg/kg/week, subcutaneous injection, Once daily.<br>|
| Experimental: Y-shape pegylated somatropin optimal dose<br> | Drug: Y-shape pegylated somatropin<br>* Y-shape pegylated somatropin 140μg/kg, subcutaneous injection, Once weekly.<br>|
| Active Comparator: Norditropin-2<br> | Drug: Norditropin<br>* Norditropin 245μg/kg/week, subcutaneous injection, Once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: Change of areas under the curve of IGF-1 concentration from baseline (ΔIGF-1 AUC). |  | 12 weeks | 
| Phase 3: Height velocity. |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of height standard deviation score according to chronological age. |  | 52 weeks | 
| Change of height standard deviation score according to bone age. |  | 52 weeks | 
| Serum IGF-l level |  | change from baseline to 52 weeks | 
| Serum IGFBP-3 level |  | change from baseline to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth Hormone Deficiency, somatropin, recombinated human growth hormone, Growth Hormone