NCT04435158已完成1 期
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity Study Following Multiple Subcutaneous Injections of SHR-1222 in Postmenopausal Osteoporosis Patients
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 1
- 主要终点
- Safety and Tolerance: Number of subjects with adverse events
研究概览
简要总结
This is a Multi-Center, Randomized, Double-Blind, Dose Escalation, Placebo Parallel Controlled PhaseⅠClinical study to Evaluate the Safety, Tolerability and Pharmacokinetics, Pharmacodynamics, Immunogenicity with Multiple Subcutaneous Injections of SHR-1222 in Postmenopausal Osteoporosis Patients.
The primary objective of this study is to investigate the safety and tolerability of a range of subcutaneous SHR-1222 in postmenopausal osteoporosis patients. Secondary objectives are to determine the pharmacokinetics (PK), pharmacodynamics (PD) profile of SHR-1222 in postmenopausal osteoporosis patients including assessment of immunogenicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent;
- •Age ≥50 and ≤70 years old and post menopause for at least 5 years at the time of screening;
- •Weight ≥40kg at the time of screening;
- •BMD T-score ≤ -2.50 at the lumbar vertebrae, total hip or femoral neck at the time of screening, based on DXA scans;
- •At least 2 vertebrae in the L1-L4 region and at least one hip are evaluable by DXA;
- •Without disease that would significantly affect the study or bring additional health risks at the time of screening or baseline; blood pressure < 150 / 95mmHg, blood fasting blood glucose < 7.0mmol/l, glycosylated hemoglobin < 7%, or total cholesterol < 6.2mmol/l, triglyceride < 3.4mmol/l under the condition of lifestyle improvement rather than drug treatment; If there are other abnormalities in the examination report of the subject, the subject could only be included after investigator approval;
- •Ambulatory.
排除标准
- •Any disease affecting bone metabolism;
- •Any severe (SQ3) or more than 2 moderate (SQ2) vertebral fractures, as assessed by the central imaging based on lateral spine x-rays at the time of screening;
- •History of hip fracture;
- •25 (OH) vitamin D levels < 20 ng/mL at the time of screening. Vitamin D repletion will be permitted and subjects may be rescreened;
- •BMD T-score < -3.50 at the lumber vertebra, total hip or femoral neck at the time of screening, based on DXA scans;
- •Use of the following agents affecting bone metabolism:
- •IV bisphosphonates or denosumab prior to screening;
- •Oral bisphosphonates, PTH analogs, Strontium or fluoride within 12m prior to screening;
- •Hormone replacement therapy within 6m prior to screening;
- •Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed), Anabolic steroids, Calcitriol and available analogues, thiazide diuretics within 3m prior to screening;
- •History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as hyperprolactinemia, osteosclerosis, Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome;
- •Hyperparathyroidism, hypothyroidism, hyperthyroidism, hypothyroidism, hypercalcemia, hypocalcemia, renal failure, etc at the time of screening;
- •Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years;
- •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 experimental drugs;
- •Past medical history of cerebral infarction, ischemic or hemorrhagic stroke;
- •Past medical history of Myocardial infarction, coronary heart disease, angina pectoris, heart failure (cardiac function II-IV), serious arrhythmia (such as atrial fibrillation, pacemaker needed)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma pancreatic acyl transferase (GGT) or total bilirubin, more than 2 x ULN during screening;
- •3 months prior to screening involved in any drug clinical subjects (except screening failed or not given cinical drugs) or within 5 half-lives of test drug at the time of screening;
- •Any major surgery in 1m prior to screening or a surgery plan during the study;
- •Blood donation or loss more than 400mL or blood transfusion within 3 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;
- •No history of alcohol and substance abuse or positive urine drug screening;
- •Subjects with any other situation should not be involved, which determined by the researchers.
研究组 & 干预措施
Cohort 4：SHR-1222
Experimental
Subcutaneous injection of SHR-1222 dosage 4 every 2 months × 6 months
干预措施: SHR-1222 (Drug)
Cohort 1：SHR-1222
Experimental
Subcutaneous injection of SHR-1222 dosage 1 monthly × 6 months
干预措施: SHR-1222 (Drug)
Cohort 2：SHR-1222
Experimental
Subcutaneous injection of SHR-1222 dosage 2 monthly × 6 months
干预措施: SHR-1222 (Drug)
Cohort 3：SHR-1222
Experimental
Subcutaneous injection of SHR-1222 dosage 3 monthly × 6 months
干预措施: SHR-1222 (Drug)
Cohort 5：SHR-1222
Experimental
Subcutaneous injection of SHR-1222 dosage 5 every 2 months × 6 months
干预措施: SHR-1222 (Drug)
Cohort 6：placebo
Experimental
Subcutaneous injection of placebo × 6 months
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and Tolerance: Number of subjects with adverse events
时间窗: Dose administration to 225 days after first dose administration
Number \& proportion of subjects with adverse events
次要结局
- Antidrug antibody(Pre-dose to 225 days after first dose administration)
- Assessment of PK parameter-area under curve (AUC)(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in areal bone mineral density of total hip from baseline by dualenergy X-ray absorptiometry(Pre-dose to 225 days after first dose administration)
- Assessment of PK parameter-maximum concentration (Cmax)(Pre-dose to 225 days after first dose administration)
- Assessment of PK parameter-time to maximum concentration (Tmax)(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in osteocalcin from baseline(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in serum totol sclerostin(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in areal bone mineral density of lumbar spine (L1-L4) from baseline by dualenergy X-ray absorptiometry(Pre-dose to 225 days after first dose administration)
- Assessment of PD parameter-change in areal bone mineral density of collum femoris from baseline by dualenergy X-ray absorptiometry(Pre-dose to 225 days after first dose administration)
- Neutralizing Antibody(Pre-dose to 225 days after first dose administration)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
1 期
The PK/PD Study of A Single Subcutaneous Injection of SHR-1209 in Healthy SubjectsHypercholesteremiaNCT03634436Jiangsu HengRui Medicine Co., Ltd.32
已完成
1 期
Safety, Tolerability, Pharmacodynamic Effects and Preliminary Evidence for Efficacy of the Anti-Hypertension Vaccine CYT006-AngQbEssential HypertensionNCT00500786Cytos Biotechnology AG88
已完成
2 期
A Study of Multiple Doses of AbGn-168H by Intravenous Infusion in Patients With Moderate to Severe Chronic Plaque PsoriasisModerate to Severe Chronic Plaque PsoriasisNCT02223039AbGenomics B.V Taiwan Branch50
已完成
3 期
Study of Efficacy and Safety of HLX03 in Subjects With Moderate to Severe Plaque PsoriasisPlaque PsoriasisNCT03316781Shanghai Henlius Biotech262
已完成
2 期
Phase IIa Study of Multiple Doses of AbGn-168H by iv Infusion in Moderate to Severe Chronic Plaque Psoriasis PatientsModerate to Severe Chronic Plaque PsoriasisNCT01855880AbGenomics B.V Taiwan Branch54