A Study of PEG-somatropin in the Treatment of Children With Idiopathic Short Stature

Study Overview
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Brief Summary
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This study aims to explore the optimal dose of pegylated recombinant human growth hormone (PEG-rhGH) injection to treat children with idiopathic short stature (ISS), evaluate its safety and efficacy, and provide scientific and reliable evidence for the medication dosage in Phase III clinical study.

Official Title
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Pegylated Somatropin (PEG Somatropin) in the Treatment of Children With Idiopathic Short Stature: A Controlled, Prospective, Randomized, Multicenter Phase-II Study With An Untreated Control Group.

Conditions
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Dwarfism

Intervention / Treatment
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* Drug: Jintrolong® low dose group
* Drug: Jintrolong® high dose group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Boys are between 4 and 9 years of age and girls are between 4 and 8 years of age. Height <-2 SD for chronological age. Growth velocity<5.0 cm/yr. GH peak concentration ≥10.0 ng/mL in two different stimulation tests. The difference of bone age (BA) and chronological age (CA) is within -2 to +2. IGF-1 concentration is between -2 SDS to +2 SDS. Prepubertal Status(Tanner Stage I). Birth weight within the normal range. Growth hormone treatment-naive. Subjects are willing and able to cooperate to complete scheduled visits, treatment plans and laboratory tests and other procedures, to sign informed consent. Exclusion Criteria: Subjects with abnormal liver and kidney functions (ALT > upper limit of normal value; Cr > upper limit of normal value). Subjects are positive for anti-HBc, HbsAg or HbeAg in Hepatitis B virus tests. Subjects with known highly allergic constitution or allergy to investigational product or its excipient. Subjects with systemic chronic disease and immune deficiency. Patients diagnosed with tumor. Patients with mental disease. Patients with other types of abnormal growth and development. Growth hormone deficiency (GHD) (confirmed by GH stimulation test); Turner syndrome (confirmed by karyotype test of girls); Noonan syndrome (hypertelorism, pectus carinatum, hypophrenia, frequently with skin disease and congenital heart disease, missense mutation of the protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene on chromosome 12 for half of the patients, for both male and female patients); Laron sydrome (confirmed by IGF-1 generation test); Small for gestational age ( the birth height or weight is below the tenth percentile or 2 SD, with catch-up growth uncompleted at 2 years old). Growth disorders caused by malnutrition or hypothyroidism (thyroid function test). Congenital skeletal abnormalities or scoliosis, claudication. Subjects with impaired glucose regulation (IGR) (including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) ) or diabetes). Subjects with abnormal electrolyte, blood gas analysis (vein), creatine kinase. Subjects who took part in other clinical trials within 3 months. Subjects who received medications which may interfere GH secretion or GH function, or other hormones within 3 months (such as sex steroids, glucocorticoids, etc.). For patients with potential high tumor risks such as tumor markers exceed normal range and some other relative information, they may be excluded from the treatment. Other conditions which is inappropriate for this study in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 9 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: Jintrolong® low dose group<br>PEG-rhGH Injection (27IU/4.5mg/0.5ml/bottle) 0.1 mg/kg/w by subcutaneous injection for 52 weeks. | Drug: Jintrolong® low dose group<br>* PEG-somatropin 0.1mg/kg/wk by weekly subcutaneous injection for 52 weeks.<br>* Other names: PEG-somatropin;Drug: Jintrolong® high dose group<br>* PEG-somatropin 0.2 mg/kg/wk by weekly subcutaneous injection for 52 weeks.<br>* Other names: PEG-somatropin;|
| Experimental: Jintrolong® high dose group<br>PEG-rhGH Injection (27IU/4.5mg/0.5ml/bottle) 0.2 mg/kg/w by subcutaneous injection for 52 weeks. | Drug: Jintrolong® low dose group<br>* PEG-somatropin 0.1mg/kg/wk by weekly subcutaneous injection for 52 weeks.<br>* Other names: PEG-somatropin;Drug: Jintrolong® high dose group<br>* PEG-somatropin 0.2 mg/kg/wk by weekly subcutaneous injection for 52 weeks.<br>* Other names: PEG-somatropin;|
| No Intervention: Negative control group<br>Untreated Control Group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Height Standard Deviation Score for Chronological Age (ΔHtSDSCA) | Change in Height Standard Deviation Score for Chronological Age (ΔHtSDSCA) from Baseline to 52 weeks；ΔHtSDSCA=(height Yx - reference mean for CA Yx) / reference SD for CA Yx (Yx refers to the height value at particular timepoint x) | Baseline，52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Annualized Height Velocity | Annualized Height Velocity=12×(Height Yx - Height at Baseline)/(Date of Yx - Date of Baseline) (Yx refers to the height value at particular timepoint x) | Baseline，52 weeks | 
| Change in Bone Maturation | Bone Maturation=(BA Yx-BA at Baseline)/(Date of Yx - Date of Baseline) (Yx refers to the BA value at particular timepoint x) | Baseline，52 weeks | 
| Change in IGF-1 Standard Deviation Score (IGF-1 SDS) | GF-1 SDS=(IGF-1 Yx - reference mean for CA Yx) / reference SD for CA Yx (Yx refers to the IGF-1 value at particular timepoint x) | Baseline，52 weeks | 
| IGF-1/IGFBP-3 molar ratio at 52 weeks | IGF-1/IGFBP-3 molar ration=[IGF-1(ng/ml)/7.6]/[IGFBP-3 (ng/ml)/25.75] | Baseline，52 weeks |