Efficacy and Safety of rhGH (Jintropin®) in Pediatric Participants With ISS

Study Overview
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Brief Summary
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Phase 1: To evaluate the safety and efficacy of 0.05mg/kg/d of rhGH (Jintropin®) in the treatment of children with idiopathic short stature (ISS) in 52 weeks. Phase 2: To evaluate the safety and efficacy of rhGH (Jintropin®) in the treatment of children with ISS in 2 years

Official Title
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Phase 2 Study of Efficacy and Safety of rhGH (Jintropin®) in Pediatric Participants With ISS (Idiopathic Short Stature): a 52-week Multicenter, Open-label, Randomized, Negative Controlled Study Followed by a 52-week Open-label Period

Conditions
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Dwarfism

Intervention / Treatment
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* Other: Negative control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Boys are between 4 and 10 years old age and girls are between 4 and 9 years old age; Height <-2.25 SD (Standard deviation) for chronological age; GH (Growth hormone) peak concentration ≥10.0 ng/mL in GH stimulation tests; The bone age (BA) ≤chronological age (CA)+6 months; Prepubertal Status (Tanner Stage I); Birth weight within the normal range; Growth hormone treatment-naive; Participants are willing and able to cooperate to complete scheduled visits, treatment plans and laboratory tests and other procedures, to sign informed consent. Exclusion Criteria: Participants with abnormal liver and kidney functions (ALT > upper limit 1.5 times of normal value; Cr > upper limit of normal value); Participants are positive for anti-HBc, HbsAg or HbeAg in Hepatitis B virus tests; Participants with known highly allergic constitution or allergy to investigational product or its excipient; Participants with systemic chronic disease and immune deficiency; Participants diagnosed with tumor, or with potential high tumor risks such as tumor markers exceed normal range and some other relative information may be excluded from the treatment; Participants with mental disease; Participants 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 participants, for both male and female participants); Laron syndrome (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). Participants with impaired glucose regulation (IGR) (including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) ) or diabetes; BMI (Body mass index) ≥22kg/m²; Congenital skeletal abnormalities or scoliosis, claudication; Participants who took part in other clinical trials within 3 months; Participants who received medications which may interfere GH secretion or GH function, or other hormones within 3 months (such as sex steroids, glucocorticoids, etc.); 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: 10 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: rhGH/Jintropin AQ<br>Jintropin AQ, injection, 30IU/10mg/3ml/cartridge, 0.05mg /kg/d in phase 1 and 0.05-0.07mg/kg/d in phase 2. | Other: Negative control<br>* Untreated-control group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ΔHtSDSca (The change of height standard deviation score of chronological age before and after treatment) | ΔHtSDSca was the difference of HtSDSca before and after treatment, and HtSDSca was calculated by dividing the difference between the actual height of a patient and the mean height of the population for that chronological age by the standard deviation (SD) of the height of the population for that chronological age. | Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ΔHT (Change of height) |  | Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2. | 
| △BA/CA (bone age change / chronological age) |  | Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2. | 
| Yearly growth velocity |  | Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2. | 
| ΔIGF-1 SDS (Change of insulin-like growth factor 1 standard deviation score) |  | Baseline, 4,13,26,39,52,65,78,91,104 weeks after initiating treatment, 52 weeks in phase 1; 2 years in phase 2. |