Phase 1, Randomized, Open Label, Three-arm, Single Dose, Parallel Group Study to Compare AZD7442 (AZD8895 + AZD1061) Pharmacokinetic Exposure Following Intramuscular Administration as a Co-formulation Versus Administration From Two Separate Vials of the Individual Monoclonal Antibodies in Adult Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 224
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
研究概览
简要总结
The study will assess pharmacokinetic (PK) comparability between different formulations of AZD7442, which is a combination of two individual monoclonal antibodies (mAbs), AZD8895 and AZD1061.
详细描述
This is a randomized, open label, three-arm, single dose, parallel group, multi-center, PK comparability study.
Eligible healthy participants will be randomized in a 1:1:1 ratio between the 3 treatment groups. Each participant will receive AZD7442 as either a single intramuscular (IM) dose (co-formulation; AZD8895 + AZD1061), or as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) from either clonal cell line material or cell pool material.
Following an observation and PK and pharmacodynamic (PD) sample collection, post-dose, participants will be discharged from the Clinical Unit. During the Follow-up Period of approximately 1 year, participants will return as outpatient follow-up visits until Day 361.
The total duration of the study for a participant will be approximately 389 days comprising of a Screening Period that can last up to 28 days, Treatment Period of 1 day, and a Follow up Period of 360 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants according to medical history, physical examination, and baseline safety laboratory tests.
- •Documented negative results of a Severe Acute Respiratory Syndrome Corona Virus 2 reverse transcriptase polymerase chain reaction (SARS-CoV-2 RT-PCR) test collected ≤ 3 days prior to investigational medicinal drug (IMP) dose administration (Day 1) or a negative rapid SARS-CoV-2 antigen test on Day 1 (pre-dose).
- •Able to complete the Follow-up period up to Day 361 as required by the protocol.
- •Body weight ≥ 50 kg to ≤ 110 kg at screening and a Body mass index ≥ 18.0 to ≤ 30 kg/m^2 at the time of the Screening Visit.
排除标准
- •Known history of allergy or reaction to any component of AZD7442 (AZD8895 + AZD1061).
- •History of infection with SARS or Middle East Respiratory Syndrome.
- •Positive SARSCoV-2 result based on available data at screening or at Day
- •Any clinical signs and symptoms consistent with Corona virus disease 2019 (COVID-19), eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
- •History of clinically significant bleeding disorder.
- •Active infection with hepatitis B or C or positive test for hepatitis C or for hepatitis B surface antigen at screening.
- •Immunodeficiency due to illness, including HIV infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone.
- •Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study
- •Any prior receipt of another mAb indicated for the prevention or treatment of SARS CoV-2 or COVID-
- •Receipt of a mAb within 6 months or 5 antibody half-lives.
- •Receipt of a COVID-19 vaccination ≤ 14 days before IMP administration (Day 1) or plan to receive a COVID-19 vaccination ≤ 14 days after IMP dose (such participants can subsequently be included in the study once they have reached > 14 days after their last dose of vaccine).
研究组 & 干预措施
AZD7442 (co-formulation)
Participants will receive single dose of AZD7442 (co-formulation of AZD8895 + AZD1061) on Day 1.
干预措施: AZD7442 (Biological)
AZD8895 and AZD1061 (clonal cell line material)
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
干预措施: AZD8895 (clonal cell line material) (Biological)
AZD8895 and AZD1061 (clonal cell line material)
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
干预措施: AZD1061 (clonal cell line material) (Biological)
AZD8895 and AZD1061 (cell pool material)
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
干预措施: AZD8895 (cell pool material) (Biological)
AZD8895 and AZD1061 (cell pool material)
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
干预措施: AZD1061 (cell pool material) (Biological)
结局指标
主要结局
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
时间窗: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
The pharmacokinetic (PK \[AUCinf\]) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The AUCinf comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated. day\*micrograms per milliliter (day\*μg/mL)
Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast)
时间窗: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
The PK (AUClast) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The AUClast comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated.
Maximum Observed Serum (Peak) Concentration (Cmax)
时间窗: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
The PK (Cmax) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The Cmax comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated.
次要结局
- Time to Maximum Observed Serum Concentration (Tmax)(Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361)
- Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d)(Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, and 31)
- Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d)(Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31 and 61)
- Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d)(Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61 and 91)
- Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d)(Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61, 91, and 181)
- Time of Last Quantifiable Concentration (Tlast)(Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 382)
- Terminal Half-life (t½λz)(Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361)
- Apparent Clearance After Extravascular Administration (CL/F)(Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361)
- Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)(Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361)
- Number of Participants With Adverse Events (AEs)(From Day 1 until Follow-up visit (Day 361))
- Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies(Day 1 (Pre-dose) until Follow-up visit (Day 361))