The Efficacy and Safety of Inpegsomatropin Injection in Children With Short Stature Born Small for Gestational Age

A Multicenter, Randomized, Open-Label, Active-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Inpegsomatropin Injection, s.c Once a Week, Compared With Recombinant Human Growth Hormone (rhGH) Injection in Children With Short Stature Born Small for Gestational Age（SGA）

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 short stature born small for gestational age (SGA).It plans to enroll 141 children with short stature born small for gestational age (SGA), who will be stratified by gender and age and randomized in a 1:1:1 ratio to either Experimental Group 1, Experimental Group 2, or the Active Control Group. All participants will undergo a screening period (up to 12 weeks), a treatment period (52 weeks), and a post-treatment follow-up period (5 weeks). Safety and efficacy will be comprehensively evaluated.

Inclusion Criteria:

• Prepubertal (Tanner stage I) children: boys aged ≥2 and <11 years, and girls aged ≥2 and <10 years at screening.
• Bone age is not more than 1 year advanced or more than 2 years delayed compared to chronological age (i.e., -2 years ≤ bone age - chronological age ≤ 1 year).
• Birth weight and/or length below the 10th percentile for gestational age and sex, according to the reference values in Appendix 1.
• Gestational age at birth ≥28 weeks.
• Height at screening below -2 SD for age and sex, according to the reference values in Appendix 2.
• Body mass index (BMI) between the 5th and 95th percentiles for age and sex, according to the reference values in Appendix 3.
• Peak GH level ≥10.0 ng/mL in at least one prior GH stimulation test.
• No prior systemic growth-promoting therapy (used continuously for ≥1 month), including but not limited to growth hormone, insulin-like growth factor-1 (IGF-1), etc.
• Legal guardian has provided written informed consent. If the participant is ≥8 years old, they must also provide written assent. For participants under 8 years old who are capable of expressing agreement, their assent should be formally documented.

Exclusion Criteria:

• Subjects with closed epiphyses.
• Subjects with other types of growth abnormalities, including confirmed or highly suspected growth hormone deficiency (GHD), Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, Turner syndrome, short stature due to GH receptor deficiency, short stature due to growth plate-related gene abnormalities (e.g., SHOX gene anomalies), growth retardation due to malnutrition, or growth retardation due to hypothyroidism.
• Participation in any other clinical trial with drug or non-drug interventions within 3 months prior to screening.
• Use of inhaled corticosteroids for more than 2 consecutive weeks, or oral/intravenous corticosteroids for more than 1 consecutive week, within 3 months prior to screening.
• Current or long-term requirement for therapies that may affect growth, including but not limited to methylphenidate, sex hormones, gonadotropin-releasing hormone analogs, aromatase inhibitors, anabolic agents, or insulin.
• Abnormal liver or kidney function at screening (ALT > 1.5 times the upper limit of normal [ULN], Cr > ULN).
• Diagnosis of diabetes mellitus, or two consecutive fasting blood glucose measurements ≥ 6.1 mmol/L prior to randomization.
• Chronic infectious diseases which, in the investigator's judgment, may affect study participation (e.g., chronic hepatitis B).
• Systemic chronic diseases, such as chronic kidney disease, severe cardiovascular diseases, or psychiatric/psychological disorders.
• Congenital skeletal dysplasia, scoliosis exceeding 15°, limping gait, or a prior diagnosis of slipped capital femoral epiphysis.
• History of intracranial hypertension.
• Past or current history of malignant tumors, including intracranial tumors.
• Known allergy to growth hormone or any of its excipients.
• Any other condition deemed by the investigator as inappropriate for participation in this clinical trial.