A Study of PEG-somatropin Injection to Treat Children of Turner Syndrome

Study Overview
=================
Brief Summary
-----------------
This study aims to explore the optimal dose of pegylated recombinant human growth hormone (PEG-rhGH) injection to treat children of Turner syndrome (TS), preliminarily evaluate its safety and efficacy and provide scientific and reliable evidence for the medication dosage in Phase 3 clinical trial.

Official Title
-----------------
A Phase 2 Study of Pegylated Recombinant Human Growth Hormone Injection to Treat Children of Turner Syndrome

Conditions
-----------------
Turner Syndrome

Intervention / Treatment
-----------------
* Biological: PEG-rhGH low dose
* Biological: PEG-rhGH high dose
* Other: Non-treatment control group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female Bone age <12 years Karyotype: 45, X; 45, X / 46, XXqi; 45, X / 46, XXr; 45, X / 46, XX; 46, XXqi; 46, XXpi; 45, X / 47, XXX; 46, XXp-; 45, X / 46, XXp-; 46, XXq-; 45X / 46, XXq-; 45, X / 46, XX / 47, XXX, etc. (count 50 or more cells); Facial appearance and abnormalities: Patients with at least one of the following signs, which include but are not limited to facial pigmented nevus, short neck, webbed neck, low posterior hairline, low-set ears, micrognathia, high-voulted arch, shield-like chest, cubitus valgus, genu valgum, short 4th and 5th metacarpals, nail dysplasia, scoliosis, ptosis and strabismus, cardiovascular abnormalities (such as aortic stenosis, bicuspid aortic valve and hypertension), reproductive abnormalities (such as primary gonadal dysfunction), renal abnormalities, thyroid hypofunction, middle ear lesion, etc. Short stature: height below -2.5SD of the mean height of the same age and gender. Pre-pubertal (Tanner Stage I ) patients No history of growth hormone treatment The subject and his/her guardian sign the informed consent (if the subject is incapable to sign the informed consent, his/her legal guardian shall sign the name of the subject instead) Exclusion Criteria: Subjects with abnormal liver and kidney functions (ALT > upper limit of normal value; Cr > upper limit of normal value) Subjects positive for anti-HBc, HbsAg or HbeAg in Hepatitis B virus tests; Subjects with highly allergic constitution or allergy to proteins or investigational product or its excipient Subjects with systemic chronic disease and immune deficiency Patients diagnosed with tumor For patients whose tumor markers exceeding normal range in combination with other information, considering as potential high risks of tumor, they may be excluded from the treatment. Patients with mental disease Subjects with impaired glucose regulation (IGR) (including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) ) or diabetes Subjects who took part in other clinical trials within 3 months Subjects who received medicines which may interfere GH secretion or GH function, or other hormones within 3 months (such as sex steroids, glucocorticoids, etc.) Other conditions which are unsuitable for this study in the opinion of the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-rhGH low dose<br>PEG-rhGH Injection (27IU/4.5mg/0.5ml/bottle) 0.1 mg/kg/w by subcutaneous injection for 52 weeks. | Biological: PEG-rhGH low dose<br>* PEG-rhGH Injection 0.1 mg/kg/w by subcutaneous injection for 52 weeks.<br>* Other names: Polyethylene Glycol Recombinant Human Somatropin Injection;Biological: PEG-rhGH high dose<br>* PEG-rhGH Injection 0.2 mg/kg/w by subcutaneous injection for 52 weeks.<br>* Other names: Polyethylene Glycol Recombinant Human Somatropin Injection;Other: Non-treatment control group<br> <br> |
| Experimental: PEG-rhGH high dose<br>PEG-rhGH Injection (27IU/4.5mg/0.5ml/bottle) 0.2 mg/kg/w by subcutaneous injection for 52 weeks. | Biological: PEG-rhGH low dose<br>* PEG-rhGH Injection 0.1 mg/kg/w by subcutaneous injection for 52 weeks.<br>* Other names: Polyethylene Glycol Recombinant Human Somatropin Injection;Biological: PEG-rhGH high dose<br>* PEG-rhGH Injection 0.2 mg/kg/w by subcutaneous injection for 52 weeks.<br>* Other names: Polyethylene Glycol Recombinant Human Somatropin Injection;Other: Non-treatment control group<br> <br> |
| No Intervention: Non-treatment control group<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of height standard deviation score before and after treatment (ΔHT SDS) | The change of height standard deviation score of chronological age before and after treatment | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity | Annual growth rate at the end of treatment | 52 weeks | 
| ΔBA/ΔCA | Bone maturation (changes of bone age/ chang of chronological age) | 52 weeks | 
| IGF-1(Insulin-like growth factor 1) SDS |  | 52 weeks |