An Open-Label, Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Doses of Subcutaneously Administered Human Monoclonal Antibody Pozelimab in Combination With Single Doses of Subcutaneously Administered siRNA Cemdisiran in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment emergent adverse events (TEAEs)
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of ascending doses of subcutaneous (SC) pozelimab and SC cemdisiran when administered on the same day or sequentially 28 days apart.
The secondary objectives of the study are:
- To assess the concentration-time profiles of total pozelimab, total complement component 5 (C5), cemdisiran, and cemdisiran metabolite(s) following single ascending doses of SC pozelimab and SC cemdisiran when administered on the same day or sequentially 28 days apart
- To assess the pharmacodynamic (PD) profile of ascending doses of SC pozelimab and SC cemdisiran, as well as when administered on the same day or sequentially 28 days apart
- To assess the immunogenicity of pozelimab and cemdisiran
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Has a body mass index less than 30 kg/m2 at the screening visit
- •Judged to be in good health as defined in the protocol
- •Is in good health based on laboratory safety testing obtained at the screening visit NOTE: Subject with a history of Gilbert's disease can be enrolled in the study
- •Willing to undergo vaccination against Neisseria meningitidis unless subjects have documentation of completed series of vaccinations within the past 2 years of the screening visit
- •Must have two negative COVID-19 tests taken 48 hours apart and within 7 days prior to study drug administration
排除标准
- •History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disease, as assessed by the investigator that may confound the results of the study or poses an additional risk to the subject by study participation
- •Hospitalization (>24 h) for any reason within 30 days of the screening visit
- •Has a confirmed positive drug test result at the screening visit and/or prior to enrollment; or a history of recreational drug use (eg, marijuana) and/or drug or alcohol abuse within a year prior to the screening visit
- •Is positive for HIV, hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb), hepatitis C antibody and positive for qualitative (ie, detected) HCV RNA test at the screening visit
- •Within the previous 2 months of the screening visit has a history of bacterial, protozoal, parasitic or viral infection (including COVID-19) and/or persistent chronic or active recurring infection which requires treatment with antibiotics, antivirals, or antifungals
- •Known or suspected COVID-19 disease
- •Known allergy or intolerance to penicillin class antibiotics or macrolides
- •NOTE: Other protocol-defined Inclusion/ Exclusion criteria apply
研究组 & 干预措施
Cohort 1
Cemdisiran at dose 1 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29
干预措施: Pozelimab (Drug)
Cohort 1
Cemdisiran at dose 1 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29
干预措施: Cemdisiran (Drug)
Cohort 2
Cemdisiran at dose 2 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29
干预措施: Pozelimab (Drug)
Cohort 2
Cemdisiran at dose 2 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29
干预措施: Cemdisiran (Drug)
Cohort 3
Cemdisiran at dose 2 SC single dose and pozelimab at dose 2 SC single dose, both administered on day 1
干预措施: Pozelimab (Drug)
Cohort 3
Cemdisiran at dose 2 SC single dose and pozelimab at dose 2 SC single dose, both administered on day 1
干预措施: Cemdisiran (Drug)
结局指标
主要结局
Incidence and severity of treatment emergent adverse events (TEAEs)
时间窗: Up to 20 weeks
次要结局
- Concentrations of total C5 over time(Up to 20 weeks)
- Concentrations of pozelimab in serum over time(Up to 20 weeks)
- Concentrations of cemdisiran in plasma over time(Up to 20 weeks)
- Change from baseline in total complement hemolytic activity assay (CH50) over time(Up to 20 weeks)
- Incidence of treatment-emergent anti-drug antibodies (ADA) to pozelimab(Up to 20 weeks)
- Incidence of treatment-emergent anti-drug antibodies (ADA) to cemdisiran(Up to 20 weeks)