The PK/PD Study of A Single Subcutaneous Injection of SHR-1222 in Healthy Subjects
- Registration Number
- NCT03870100
- Lead Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 3 SHR-1222 A single subcutaneous injection of SHR-1222 dose 3 versus placebo Cohort 2 Placebo A single subcutaneous injection of SHR-1222 dose 2 versus placebo Cohort 1 SHR-1222 A single subcutaneous injection of SHR-1222 dose 1 versus placebo Cohort 1 Placebo A single subcutaneous injection of SHR-1222 dose 1 versus placebo Cohort 2 SHR-1222 A single subcutaneous injection of SHR-1222 dose 2 versus placebo Cohort 3 Placebo A single subcutaneous injection of SHR-1222 dose 3 versus placebo Cohort 4 SHR-1222 A single subcutaneous injection of SHR-1222 dose 4 versus placebo Cohort 4 Placebo A single subcutaneous injection of SHR-1222 dose 4 versus placebo Cohort 5 SHR-1222 A single subcutaneous injection of SHR-1222 dose 5 versus placebo Cohort 5 Placebo A single subcutaneous injection of SHR-1222 dose 5 versus placebo
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 by dualenergy X-ray absorptiometry
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 by dualenergy X-ray absorptiometry
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 by quantitative computed tomography
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 by quantitative computed tomography
Antidrug antibody concentration Pre-dose to 85 days after dose administration
Trial Locations
- Locations (1)
2nd Xiangya Hospital of Central South University
🇨🇳Changsha, China