Osteoporosis
Conditions
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.
Interventions
DRUGSHR-1222
Pharmaceutical form: water injection Route of administration: subcutaneous
DRUGPlacebo
Pharmaceutical form: water injection Route of administration: subcutaneous
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 59 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 PK parameter-time to maximum concentration (Tmax) | 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 | by dualenergy X-ray absorptiometry |
| 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 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 | — |
| Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline | Pre-dose to 85 days after dose administration | — |
Countries
China
Outcome results
None listed