A Study to Evaluating the Efficacy and Safety of Recombinant Long-acting Human Growth Hormone (TJ101) in Children With Growth Hormone Deficiency

Study Overview
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Brief Summary
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A Phase III, Randomized, open-label, positive-drug parallel control, Study to Evaluate the Efficacy and Safety of TJ101 in Child subject with growth hormone deficieney.

Official Title
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A Phase III, Randomized, Open-label, Positive-controlled, Multi-center Study to Evaluating the Efficacy and Safety of Recombinant Long-acting Human Growth Hormone (TJ101) in Children With Growth Hormone Deficiency

Conditions
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Pediatric Growth Hormone Deficiency

Intervention / Treatment
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* Drug: TJ101
* Drug: NordiFlex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Boys: 3 years ≤ boy's age ≤ 10 years；Girls: 3 years ≤ girl's age ≤ 9 years Pre-pubertal children(Tanner stage I) GHD confirmed by 2 different GH provocation tests with peak GH concentration below 10 ng/mL in screening or one month Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age (CA) and gender according to Table of standard deviation unit values of age and height of Chinese children aged 3-12 years , (HT SDS ≤ -2.0) Height velocity≤5.0cm/years (Including height records before at least three months)； IGF-1 SDS≤-1.0 Bone age (BA) is no more than two chronological age Body mass Index (BMI) must be within ±2 SD of mean BMI for the chronological age and sex according to Table of standard deviation unit values of Age and BMI of Chinese children aged 3-12 years Without prior exposure to any rhGH therapy For children with growth hormone deficiency that is one of its multiple pituitary hormone deficiencies, alternative therapies targeting the hypothalamus-pituitary-target gland axis must be used for at least 3 months before screening Written informed consent of the parent or legal guardian of the subject and assent of the subject (if the subject can read) Exclusion Criteria: beyond physiological dosage of glucocorticoid therapy Evidence of closed epiphyses Any other chronic condition that can cause short stature and cannot be treated with hormone replacement therapy(Including but not limited Chronic kidney disease, malnutrition, absorption disorders, uncontrolled hypothyroidism, celiac disease, rickets and social-psychological dwarfism) Abnormal liver and renal function (ALT>1.5 times the upper limit of normal range and Cr exceeding the upper limit of normal range) Presence of anti-hGH antibodies at screening Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, with the exception of ADHD(attention deficit hyperactivity disorder) drug hormone replacement therapies [thyroxine, hydrocortisone, desmopressin (DDAVP)] Mutations in growth hormone receptors are suspected, or any syndrome that causes insensitivity to growth hormone At screening, ophthalmologic examination (including fundus microscopy) indicated increased intracranial pressure and/or retinopathy. At screening, previous or existing intracranial tumor growth was confirmed by cranial magnetic resonance imaging (MRI) scan (using contrast agent) (MRI results up to 1 year prior to screening were acceptable) Diseases such as severe cardiopulmonary, blood system, malignant tumor or potential tumor (family history), or systemic infection, low immune function and mental diseases Significant spinal abnormalities, including scoliosis (Cobb Angle & GT;60 ˚), kyphosis and spina bifida. Subjects diagnosed with type 2 or type 1 diabetes who were considered to have received no standard treatment, did not follow their prescribed treatment, or exhibited poor metabolic control, or had fasting glucose > 5.6 mmol/L twice in a row Chromosomal abnormalities and medical syndromes (Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, SHOX mutations/deletions and skeletal dysplasias), with the exception of septo-optic dysplasia Children with low birth weight (birth weight and/or body length are 2 SD below average according to the standard of the general Chinese population of the same gestational age and sex) The subject and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct Subject who has received an investigational product or has participated in a clinical study within 30 days before screening or during the clinical trials. Known or suspected to be HIV positive, serologically positive for syphilis, or other chronic infectious diseases, such as AIDS, tuberculosis, hepatitis, etc The history of drug, drug or alcohol abuse Other conditions not considered suitable for inclusion by the researchers

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 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: TJ101<br>TJ101 1.2 mg/kg once a week for 52weeks | Drug: TJ101<br>* TJ101/ Recombinant Human Somatropin Injection treatment: after screening, subjects will be randomized to receive TJ101 1.2 mg/kg once a week until 52 weeks back site, investigator evaluate effectiveness and safety.<br>|
| Active Comparator: NordiFlex<br>NordiFlex Injection 0.034 mg/kg once a day for 52 weeks | Drug: NordiFlex<br>* TJ101/ Recombinant Human Somatropin Injection treatment: after screening, subjects will be randomized to receive Recombinant Human Somatropin Injection 0.034 mg/kg once a day, until 52 weeks back site, investigator evaluate effectiveness and safety.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Annualized Height velocity at 52 week | The Annualized Height velocity at 52 week | 52weeks after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in Annualized Height velocity at 26 week (compared to Baseline value) |  | 26weeks after first dose | 
| change in Annualized Height velocity at 52 week (compared to Baseline value) |  | 52weeks after first dose |