A Phase 1, Open-Label Study to Investigate Drug-Drug Interaction (DDI) Potential of Nipocalimab With Coadministration of Etanercept or Hydroxychloroquine in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Part 1: Ratio of Area Under the Concentration-time Curve (AUCR) of Etanercept
研究概览
简要总结
The primary purpose of this study is to assess the effect of nipocalimab on the pharmacokinetic (PK) of etanercept (Part 1); and to assess the effect of hydroxychloroquine (HCQ) on total serum immunoglobin G (IgG) reduction by nipocalimab (Part 2) in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. If there are any abnormalities, they must be consistent with the underlying illness in the study population or considered not clinically relevant and this determination must be recorded in the participant's source documents and initialed by the investigator
- •Healthy on the basis of clinical laboratory tests performed at screening (including immunoglobulin [Ig]G) and at admission to the study site. If the results of the serum chemistry panel, liver panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
- •Good venous access in both arms
- •Participants must have heart rate of at least 50 beats per minute
- •Participant is considered eligible according to the following tuberculosis (TB) screening criteria (for Part 1 only): a) have no history of latent or active TB before screening; b) have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; c) have had no recent close contact with a person with active TB; d) have a negative QuantiFERON-TB test result within 28 days prior to the administration of study intervention
- •Part 1: Body mass index (BMI) greater than or equal to (>=) 18.0 to less than or equal to (<=) 30.0 kilogram (kg)/meter (m)^2 (inclusive), and body weight >= 50 to <= 110.0 kg (inclusive) at the screening visit and on Day -1; Part 2: BMI >= 18.0 to <= 30.0 kg/m^2 (inclusive), and body weight >= 61.5 to <= 110.0 kg (inclusive) at the screening visit and on Day -1
- •A female participant must have a negative serum (beta-human chorionic gonadotropin) test at screening and a urine pregnancy test at Day -1 prior to administration of study intervention
- •It is recommended that participants are up to date on age-appropriate vaccinations prior to screening per routine local medical guidelines. For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, applicable local vaccine labeling, guidelines, and standards of care for participants receiving immune-targeted therapy should be followed when determining an appropriate interval between vaccination and study enrollment
排除标准
- •Has a history of liver or renal insufficiency; cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- •Has a history of retinal and macular disease (only for Part 2)
- •Has shown a previous severe immediate hypersensitivity reaction response, including anaphylaxis, to therapeutic proteins (example, monoclonal antibody [mAbs])
- •Has serum albumin levels < 30 grams/Liter (g/L) at screening and Day -1
- •Has a history of myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks prior to screening
研究组 & 干预措施
Part 1: Etanercept and Nipocalimab
Participants will receive a single subcutaneous (SC) dose of etanercept on Day 1 in Period 1 followed by single intravenous (IV) infusion of nipocalimab on Day 29, SC administration of etanercept followed by an IV infusion of nipocalimab on Day 43 and then a single dose of nipocalimab IV infusion on Day 57 in Period 2 of Part 1. There will be a wash-out period of 28 days between Day 1 of Period 1 and Day 29 of Period 2 in Part 1.
干预措施: Etanercept (Drug)
Part 2 (Cohort 1): Nipocalimab
Participants will receive a single IV infusion of nipocalimab on Day 1 in Cohort 1 of Part 2.
干预措施: Nipocalimab (Drug)
Part 1: Etanercept and Nipocalimab
Participants will receive a single subcutaneous (SC) dose of etanercept on Day 1 in Period 1 followed by single intravenous (IV) infusion of nipocalimab on Day 29, SC administration of etanercept followed by an IV infusion of nipocalimab on Day 43 and then a single dose of nipocalimab IV infusion on Day 57 in Period 2 of Part 1. There will be a wash-out period of 28 days between Day 1 of Period 1 and Day 29 of Period 2 in Part 1.
干预措施: Nipocalimab (Drug)
Part 2 (Cohort 2): Nipocalimab and Hydroxychloroquine (HCQ)
Participants will receive a single oral dose of HCQ film-coated tablets once daily from Day 1 to Day 22 and a single IV infusion of nipocalimab on Day 8 in Cohort 2 of Part 2.
干预措施: Nipocalimab (Drug)
Part 2 (Cohort 2): Nipocalimab and Hydroxychloroquine (HCQ)
Participants will receive a single oral dose of HCQ film-coated tablets once daily from Day 1 to Day 22 and a single IV infusion of nipocalimab on Day 8 in Cohort 2 of Part 2.
干预措施: Hydroxychloroquine (Drug)
结局指标
主要结局
Part 1: Ratio of Area Under the Concentration-time Curve (AUCR) of Etanercept
时间窗: Up to Day 99
AUCR is defined as the ratio of area under the concentration-time curve.
Part 1: Area Under the Concentration-time Curve of Etanercept from Time Zero to Time of Last Observed Quantifiable Concentration (AUC [0-Last])
时间窗: Up to Day 99
AUC (0-last) is defined as area under the concentration-time curve of etanercept from time zero to time of last observed quantifiable concentration.
Part 1: Apparent Volume of Distribution (Vdz/F) of Etanercept
时间窗: Up to Day 99
Vdz/F is defined as apparent volume of distribution based on the terminal phase after an SC dose, calculated as dose/lambda(z)\*AUC(0-infinity).
Part 1: Serum Etanercept Concentration
时间窗: Up to Day 99
Serum etanercept concentration will be reported.
Part 1: Ratio of Maximum Observed Concentration (CmaxR) of Etanercept
时间窗: Up to Day 99
CmaxR is defined as ratio of maximum observed concentration of etanercept.
Part 1: Total Apparent Clearance (CL/F) of Etanercept
时间窗: Up to Day 99
CL/F is total apparent clearance of etanercept following subcutaneous (SC) administration, calculated as dose/AUC (0-infinity).
Part 1: Time to Reach the Last Observed Measurable Analyte Concentration (Tlast) of Etanercept
时间窗: Up to Day 99
Tlast is defined as time to reach the last observed measurable analyte concentration of etanercept.
Part 2: Change from Baseline in Total Serum Immunoglobulin (Ig) Levels
时间窗: Baseline up to Day 50
Change from baseline in total serum Ig levels (serum IgG and IgG subtypes) through Day 50 will be reported.
Part 1: Maximum Observed Concentration (Cmax) of Etanercept
时间窗: Up to Day 99
Cmax is defined as maximum observed concentration of etanercept.
Part 1: Time to Reach the Maximum Observed Concentration (Tmax) of Etanercept
时间窗: Up to Day 99
Tmax is defined as time to reach the maximum observed concentration of etanercept.
Part 1: Elimination Half-life (t1/2) of Etanercept
时间窗: Up to Day 99
t1/2 is defined as elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve, calculated as 0.693/ lambda(z).
Part 1: Area Under the Concentration-time Curve of Etanercept from Time Zero to Infinite time (AUC [0-Infinity])
时间窗: Up to Day 99
AUC (0-Infinity) is defined as area under the concentration-time curve of etanercept from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z) where AUC (0-last) is area under the concentration-time curve of etanercept from time zero to time of last observed quantifiable concentration and C(last) is the last observed quantifiable concentration, and lambda(z) is apparent terminal elimination rate constant.
次要结局
- Part 1: Number of Participants with Adverse Events (AEs)(Up to 4 months)
- Parts 1 and 2: Serum Nipocalimab Concentrations(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Part 1: Number of Participants with Abnormalities in Clinical Laboratory Tests(Up to 4 months)
- Parts 1 and 2: Cmax of Nipocalimab(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Parts 1 and 2: Volume of Distribution (Vdz) of Nipocalimab(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Part 1: Number of Participants with Abnormalities in Vital Sign Measurements(Up to 4 months)
- Parts 1 and 2: t1/2 of Nipocalimab(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Part 2: Serum Lipid and Albumin Levels(Up to Day 50)
- Part 1: Number of Participants with Abnormalities in Physical Examinations(Up to 4 months)
- Part 1: AUCR of Nipocalimab(Up to Day 99)
- Parts 1 and 2: AUC (0-Last) of Nipocalimab(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Parts 1 and 2: Total Systemic Clearance of Nipocalimab (CL)(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Part 1: CmaxR of Nipocalimab(Up to Day 99)
- Parts 1 and 2: AUC (0-Infinity) of Nipocalimab(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Parts 1 and 2: Tlast of Nipocalimab(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Parts 1 and 2: Tmax of Nipocalimab(Up to Day 99 (Part 1); up to Day 50 (Part 2))
- Part 1: Number of Participants with Antibodies to Nipocalimab(Up to Day 99)
- Part 2: Number of Participants with Receptor Occupancy (RO) Levels of Nipocalimab(Up to Day 50)