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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: SHR-1222
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>A single subcutaneous injection of SHR-1222 dose 1 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>|
| Experimental: Cohort 2<br>A single subcutaneous injection of SHR-1222 dose 2 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>|
| Experimental: Cohort 3<br>A single subcutaneous injection of SHR-1222 dose 3 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>|
| Experimental: Cohort 4<br>A single subcutaneous injection of SHR-1222 dose 4 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>|
| Experimental: Cohort 5<br>A single subcutaneous injection of SHR-1222 dose 5 versus placebo | Drug: SHR-1222<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: water injection Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number & proportion of subjects with adverse events [Time Frame: dose administration to 85 days after dose administration] Safety and Tolerance: Number & proportion of subjects with adverse events |  | Dose administration to 85 days after dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter-time to maximum concentration (Tmax) |  | Pre-dose to 85 days after dose administration | 
| Assessment of PK parameter-maximum concentration (Cmax) |  | Pre-dose to 85 days after dose administration | 
| Assessment of PK parameter-area under curve (AUC) |  | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline |  | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline |  | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in osteocalcin from baseline |  | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline |  | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in areal bone mineral density of lumbar spine (L1-L4 mean T value) from baseline | by dualenergy X-ray absorptiometry | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in areal bone mineral density of collum femoris (T value) from baseline | by dualenergy X-ray absorptiometry | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in volumetric bone mineral density of lumbar spine (L1-L4 mean T value) from baseline | by quantitative computed tomography | Pre-dose to 85 days after dose administration | 
| Assessment of PD parameter-change in volumetric bone mineral density of collum femoris (T value) from baseline | by quantitative computed tomography | Pre-dose to 85 days after dose administration | 
| Antidrug antibody concentration |  | Pre-dose to 85 days after dose administration |