GB06 Phase III Trial for Pediatric Growth Hormone Deficiency

Growth hormone deficiency (GHD) in children is characterized by short stature with a low annual height growth rate. GHD also alters body composition, including loss of lean body mass, increased abdominal visceral fat deposition, and a higher waist-to-hip ratio. Patients with GHD may also have hyperlipidemia and atherosclerosis, left ventricular dysfunction, hypertension, and elevated plasma fibrinogen levels, leading to increased cardiovascular and cerebrovascular risk. In addition, GHD can also affect cognitive function and overall well-being. These patients are also more likely to experience low energy, difficulty in concentration, social isolation, and depression.

Growth hormone (GH) supplementation is the ideal treatment for patients with GHD, and the above-mentioned abnormalities can also be improved after GH therapy. Recombinant human GH has been approved for the treatment of GHD and used for more than 30 years with favorable efficacy and safety. GB06, developed by Kexing Biopharm Co., Ltd., is a biosimilar of Norditropin®FlexProTM. Its effectiveness and safety have been verified in phase I clinical studies. This study aims to further assess the comparability of the efficacy and safety of GB06 and Norditropin®FlexProTM in pediatric patients with GHD.

Inclusion criteria

• The legal guardian of the participant understands and signs the written informed consent form (ICF); Participants over 8 years old are also required to sign the ICF, and if they are under 8 years old but can express consent, their opinions should be clearly documented.
• Age ≥ 3 years old and ≤ 11 years old (boys) or ≤ 10 years old (girls);
• Height below two standard deviations (SD) of the average height of children of the same age and gender;
• Annual height velocity (AHV) <5cm/year, based on height within 6 months to 18 months before screening;
• Body mass index (BMI) within the average ±2 SD of healthy children of the same age and gender;
• Short stature with normal intellectual development;
• Tanner stage I (testicular volume <4ml for boys, no palpable breast gland tissue for girls);
• IGF-1 level below the reference value corresponding to -1SDS for children of the same age and gender;
• Bone age lags behind the chronological age;
• Diagnosis as GHD by GH stimulation test with two different drugs within 12 months before screening, and the peak GH level ≤ 10.0ng/ml;
• A standard karyotype of 46, XX for girls.

Exclusion criteria

• Known allergy to ingredients of the study drug;
• Previous treatment with recombinant human growth hormone (rhGH) or IGF-1 or combination with other treatments that may affect growth;
• Administration of any investigational drug within 3 months before screening or participation in another clinical trial before randomization;
• Small for gestational age;
• Epiphyseal closure;
• Congenital intracranial hypertension;
• Slipped capital femoral epiphysis;
• GHD secondary to another pituitary hormone deficiency;
• Previous history or current diagnosis of malignancy (including intracranial tumors); Intracranial tumors must be confirmed by magnetic resonance imaging or computed tomography;
• History of fundus lesions (optic nerve papilledema lesions);
• Diagnosis of diabetes, or fasting blood glucose ≥ 7.0 mmol/L or hemoglobin A1c (HbA1c) ≥ 6.5%;
• Administration of systemic corticosteroid therapy consecutively for more than 2 weeks within 3 months before screening;
• Expected requirement to inhale budesonide >400μg/day or equivalent dose of inhaled glucocorticoid therapy for more than four consecutive weeks during the trial;
• Other growth abnormalities or abnormalities that may affect height, including but not limited to: chromosomal aneuploidy, Turner syndrome, Lehren's syndrome, Noonan syndrome, Prader-Willi syndrome, SHOX-1 gene abnormality, GH receptor deletion, or other significant genetic mutations causing short stature; Significant spinal abnormalities, including but not limited to scoliosis, kyphosis, and spina bifida; Congenital anomalies (resulting in skeletal abnormalities), including but not limited to Russell-Silver syndrome and bone dysplasia; Family history of bone dysplasia;
• Other clinically significant abnormalities that may affect growth or assessment of growth capacity, including but not limited to hepatic and renal dysfunction [e.g., alanine aminotransferase (ALT)> 1.5 times the upper limit of normal, creatinine (Cr) >upper limit of normal value], malnutrition, severe cardiopulmonary and hematological diseases, systemic infection, immunodeficiency, mental abnormalities, and other congenital malformations;
• Infectious diseases, such as hepatitis B, hepatitis C, AIDS, syphilis, and tuberculosis. Hepatitis B virus DNA levels will be assessed in individuals who are positive for HBV surface antigen.

A hepatitis C virus RNA test is required if the hepatitis C virus antibody test is positive. Quantitative results below the lower limit of detection will be excluded.

• Concomitant use of other treatments that may affect growth, including but not limited to methylphenidate for attention deficit hyperactivity disorder;
• History of drug or alcohol abuse;
• Children with hypothyroidism and/or adrenal insufficiency who have not received adequate stable replacement therapy lasting at least 90 days before randomization;
• Other diseases that the investigator believes may endanger the safety of the participant or protocol compliance;
• Potentially poor compliance in this study.
• Other conditions that the investigator deems unsuitable for inclusion.