The Efficacy and Safety of Inpegsomatropin Injection in Children With Idiopathic Short Stature

This is a multicenter, randomized, open-label, active-controlled Phase III clinical trial to evaluate the efficacy and safety of Inpegsomatropin injection，once a week，compared with recombinant human growth hormone (rhGH) in children with idiopathic short stature (ISS). It plans to enroll 300 children with ISS, who will be randomized , stratified by gender and age, and assigned to either the experimental group or the positive controlled group. Each participant will undergo a screening period (up to 12 weeks), a treatment period (52 weeks), and a post-treatment follow-up period (5 weeks). And the safety and efficacy will be evaluated.


Eligibility Criteria:
Inclusion Criteria:

* Prepubertal children: boys aged ≥3 years and \<11 years at screening with testicular volume \<4 mL; girls aged ≥3 years and \<10 years at screening with breast development at Tanner Stage I, i.e., no palpable breast glandular tissue.
* Bone age ≤ chronological age,with a delay of no more than 2 years compared to chronological age.
* Height at screening is below -2 standard deviations (SD) from the mean for age and sex, with height reference to Appendix 1.
* Body mass index (BMI) is within the 5th to 95th percentile for age and sex of healthy children, with reference to Appendix 2.
* Peak GH level ≥10.0 ng/ml in at least one GH stimulation test.
* No prior systemic pharmacological treatment for growth promotion (continuous use ≥1 month), including but not limited to growth hormone, insulin-like growth factor 1 (IGF-1), etc.
* The legal guardian understands and signs the informed consent form. If the participants is ≥8 years old, they must also sign the informed consent form. For participants under 8 years old who are able to express their consent, their assent should be clearly documented.

Exclusion Criteria:

* Individuals with closed epiphyses;
* Other types of growth and developmental abnormalities, including confirmed or highly suspected growth hormone deficiency (GHD), Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, Turner syndrome, small for gestational age, short stature due to SHOX gene abnormalities, growth delay due to malnutrition, growth delay due to hypothyroidism, and other short statures with a clear etiology; genetic testing results must be obtained before randomization to exclude short stature caused by definite genetic abnormalities;
* Individuals who have participated in any other clinical trial within 3 months prior to screening and have received pharmacological or non-pharmacological interventions;
* Individuals who have received inhaled corticosteroids for more than 2 consecutive weeks, or oral or intravenous corticosteroids for more than 1 week within 3 months prior to screening;
* Individuals who are currently receiving or require long-term treatment with other therapies that may affect growth, including but not limited to methylphenidate, sex hormones, gonadotropin-releasing hormone analogs, aromatase inhibitors, anabolic agents, insulin, etc.;
* Individuals with abnormal liver or kidney function at screening (ALT \> 1.5 times the upper limit of normal, Cr \> upper limit of normal);
* Individuals diagnosed with diabetes mellitus, or with fasting blood glucose ≥6.1 mmol/L on two consecutive occasions;
* Individuals with chronic infectious diseases, such as chronic hepatitis B;
* Individuals with systemic chronic diseases, such as anemia, malnutrition, hypothyroidism, chronic kidney disease, cardiovascular diseases (e.g., congenital heart disease, dilated cardiomyopathy, etc.), psychiatric disorders, or those with congenital anomalies;
* Individuals with congenital skeletal abnormalities, or those with scoliosis exceeding 15°, limping, or a history of slipped capital femoral epiphysis;
* Individuals with a history of increased intracranial pressure;
* Individuals with a history of malignancy or currently having active malignancy, including intracranial tumors;
* Individuals with severe allergic constitutions, or known allergies to growth hormone or its excipients;
* Individuals with any other disease that the investigator deems may endanger the subject's safety or compromise compliance with the study protocol.