Phase Ⅰ Clinical Study Protocol of GB223 Monoclonal Antibody Injection
Phase Ⅰ Clinical Study Protocol of GB223 Monoclonal Antibody Injection
The primary objective of this study is to evaluate the safety, tolerability and
 pharmacokinetic (PK) profiles of single dose of GB223 in healthy subjects; the secondary
 objective is to evaluate the immunogenicity and pharmacodynamic (PD) profiles of single dose
 of GB223 in healthy subjects.
Inclusion Criteria:

 1. Understand the study procedures and contents, and voluntarily sign the informed
 consent form;

 2. Aged from 18 to 65 years at ICF signing (inclusive), males or females;

 3. At screening, the male body weight≥50kg, female body weight ≥45kg, the body weight of
 males and females is not more than 75kg (inclusive), body mass index (BMI) is within
 the range between 19 and 24.0 (both inclusive);

 4. The following tests are normal, or the abnormalities are not clinically significant at
 screening: physical examination, vital sign, laboratory tests, ECG test, chest
 radiography and CT tests of upper and middle abdomen, PPD test and CT test of oral
 cavity;

 5. The subjects and their partners agree to adopt medically confirmed effective
 contraceptive measures during the entire study period and within 12 months after the
 administration of investigational products.

 6. The subjects can receive follow-up visits as scheduled, well communicate with the
 investigators and complete the study as required by the study.

 Exclusion Criteria:

 1. Lactating and pregnant women;

 2. Subjects who have pregnancy plan within 12 months;

 3. Subjects who currently or previously have osteomyelitis or osteonecrosis of jaws, or
 subjects who plan to receive invasive dental surgery or jaw surgery, or subjects whose
 wounds are not cured after dental or oral surgeries;

 4. Subjects who have clear medical history of central nervous system, cardiovascular,
 renal, hepatic, gastrointestinal, respiratory, metabolic system or subjects with other
 significant diseases; subjects who have medical history of psychiatric disorders;
 subjects with medical history of hypertension or screening systolic blood pressure ≥
 140mmHg and/or diastolic blood pressure ≥ 90mmHg, which are clinically significant at
 the discretion of the investigators; subjects who have medical history of orthostatic
 hypotension;

 5. Any of the following is met: allergic constitution; known allergic to the components
 of the investigational product or allergy history to any drug or food or pollen;
 subjects who have abnormal serum immunoglobulin E (IgE) test;

 6. Any of the current symptoms, signs or laboratory test abnormalities indicating the
 possible presence of acute or subacute infection (e.g., pyrexia, cough, urgent
 micturition, urodynia, abdominal pain, diarrhea, cutaneous infected wound etc.)

 7. Subjects who have medical history of drug addiction or drug abuse;

 8. Smoking more than 5 cigarettes/day or equivalent tobacco; or subjects who cannot stop
 smoking during the study period;

 9. Weekly alcohol consumption more than 28 units (1 unit = 285 mL of beer or 25 mL of
 spirits or 100 mL of wine); or subjects who have positive breath alcohol test within
 24 hours before the use of investigational drug;

 10. Subjects who meet any of the following criteria: alanine aminotransferase (ALT) or
 aspartate aminotransferase (AST) >1.5xULN, serum creatinine (Cr) > 1.0xULN;

 11. Abnormal routine blood tests: any of the following is met: white blood cells
 (WBC)<3.0×109/L or >9.15×109/L, neutrophil count (ANC)<1.5×109/L, platelet count
 (PLT)<100×109/L, hemoglobin (HGB)<113g/L;

 12. Abnormal serum calcium: current hypocalcaemia or hypercalcemia, or albumin-corrected
 serum calcium level is not within the normal laboratory range.

 13. Any of the following is positive: hepatitis B surface antigen (HBsAg), hepatitis C
 antibody (HCV-Ab), acquired immunodeficiency syndrome antibody (Anti-HIV) and
 anti-treponema pallidum antibody (TP-Ab);

 14. Subjects with abnormal thyroid and parathyroid function and diseases affecting bone
 metabolism such as rheumatoid arthritis and osteomalacia;

 15. Subjects with recent fracture (within 6 months);

 16. Subjects with positive tumor markers (CEA, AFP, PSA and CA-125);

 17. Patients who previously or currently have malignant tumors within 5 years before
 screening (excluding adequately treated and completely cured skin basal cell carcinoma
 or squamous cell carcinoma, cervical in situ carcinoma);

 18. Participated in other clinical studies within 3 months before enrollment, or subjects
 who received drugs which are known to injure the major organs within 3 months before
 enrollment;

 19. Participated in clinical studies of similar investigational products such as denosumab
 etc.;

 20. Use of drugs which may affect bone metabolism within 4 weeks or 5 half-lives
 (whichever is longer) before this study and the use of drugs which may affect bone
 metabolism during this study period; These drugs include but are not limited to the
 following drugs: contraceptives containing estrogen, bisphosphonate, fluoride, hormone
 replacement therapies (i.e., tibolone, estrogen, estrogenic compounds such as
 raloxifen), calcitonin, strontium, parathyroid hormone or its derivatives, vitamin D
 supplements (>1000IU/day), glucocorticoids (use of inhaled or local glucocorticoid 2
 weeks before enrollment), anabolic hormone drugs (e.g., metandienone, nandrolone
 phenylpropionate, hydroxymetholone, stanozolol, nandrolone decanoate, danazolum),
 calcitriol and diuretics;

 21. Subjects who are considered unsuitable for participating in this study for various
 reasons at the discretion of the investigator.