The PK/PD Study of A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects

Use the Protocol Title. The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study Following A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects

This is a Single Center, Randomized, Double-Blind, Dose Escalation, Placebo Parallel Controlled PhaseⅠClinical study to Evaluate the Safety, Tolerability and Pharmacokinetics, Pharmacodynamics with A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects.

The primary objective of this study is to investigate the safety and tolerability of a range of subcutaneous SHR-1222 in healthy subjects. Secondary objectives are to determine the pharmacokinetics (PK) and pharmacodynamics(PD) profile of SHR-1222 in healthy subjects including assessment of immunogenicity.

50 adult healthy subjects with 5 dose groups will be enrolled in the study, including six subjects in the lowest dose group, four of whom received the SHR-1209 and two of whom received the placebo. The other three groups have 11 subjects in each group, 9 administered SHR-1222 and 2 administered placebo. The primary endpoint is the Safety and Tolerability : adverse events, vital signs, physical examination, laboratory examination, 12 lead electrocardiogram, injection site reactions, etc.

Inclusion Criteria:

• Signed informed consent;
• Male or postmenopausal female;
• Age ≥45 and ≤59 years old;
• The body mass index (BMI) ≥18.5kg/m2 and ≤28 kg/m2;
• T value of areal bone mineral density on any lumbar spine (L1-L4) or collum femoris>-2.5 and <-1;
• The comprehensive physical examination is eligible or slightly abnormal but the researchers determine no clinical implication;
• No smoking, alcohol or drugs abuse.

Exclusion Criteria:

• Any disease affecting bone metabolism;
• Past medical history of cerebral infarction or cerebral arterial thrombosis;
• Past medical history of myocardial infarction;
• Administration of the following drugs within 6m: Hormone replacement therapy, Calcitonin Parathyroid hormone (or any derivative), Supplemental Vitamin D>1,000 IU/day, Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed), Anabolic steroids, Calcitriol and available analogues, thiazide diuretics;
• Administration of the following drugs within 12m: Bisphosphonates, Fluoride for osteoporosis;
• A bone fracture within the previous 6 months;
• A lumbar spine L1-L4 or femoral neck T-score ≤-2.5;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma pancreatic acyl transferase (GGT) or total bilirubin, more than 1.5 x ULN during screening;
• 3 months prior to screening involved in any drug clinical subjects;
• Subjects determined by the researchers have any food, dietary supplement or drugs that affect SHR-1222 absorption, distribution, metabolism and excretion in 4 weeks prior to screening or within 5 half-lives;
• Serious infection, trauma or major surgery in 4 weeks prior to screening;
• A surgery plan during the study;
• Blood donation and transfusion in 3 months prior to screening;
• Unstable thyroid dysfunction in 6 months prior to screening;
• Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive;
• Intolerant to venous blood collection;
• A clinical history of drug allergy or a history of atopic allergic diseases (asthma, urticaria, eczema dermatitis) or a known allergy to experimental or similar
• Subjects with any other situation should not be involved, which determined by the researchers.