Use the Protocol Title. The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study Following A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Cohort 1
A single subcutaneous injection of SHR-1222 dose 1 versus placebo
干预措施: SHR-1222 (Drug)
Cohort 1
A single subcutaneous injection of SHR-1222 dose 1 versus placebo
干预措施: Placebo (Drug)
Cohort 2
A single subcutaneous injection of SHR-1222 dose 2 versus placebo
干预措施: SHR-1222 (Drug)
Cohort 2
A single subcutaneous injection of SHR-1222 dose 2 versus placebo
干预措施: Placebo (Drug)
Cohort 3
A single subcutaneous injection of SHR-1222 dose 3 versus placebo
干预措施: SHR-1222 (Drug)
Cohort 3
A single subcutaneous injection of SHR-1222 dose 3 versus placebo
干预措施: Placebo (Drug)
Cohort 4
A single subcutaneous injection of SHR-1222 dose 4 versus placebo
干预措施: SHR-1222 (Drug)
Cohort 4
A single subcutaneous injection of SHR-1222 dose 4 versus placebo
干预措施: Placebo (Drug)
Cohort 5
A single subcutaneous injection of SHR-1222 dose 5 versus placebo
干预措施: SHR-1222 (Drug)
Cohort 5
A single subcutaneous injection of SHR-1222 dose 5 versus placebo
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: Dose administration to 85 days after dose administration
次要结局
- 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 collum femoris (T value) 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(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(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(Pre-dose to 85 days after dose administration)
- Antidrug antibody concentration(Pre-dose to 85 days after dose administration)