A Phase I, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of AZD1163 Administered as Single and Multiple Ascending Doses in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 108
- 试验地点
- 3
- 主要终点
- Number of participants with adverse events (AEs)
研究概览
简要总结
A study to demonstrate the safety and tolerability of AZD1163 when administered intravenously and subcutaneously in healthy participants.
详细描述
This is a first time in human (FTiH), placebo-controlled, sequential study in healthy participants. This study consists of two parts: Part 1 Single Ascending Dose (SAD) and Part 2 Multiple Ascending Dose (MAD). Part 1 will contain 9 cohorts, 8 intravenously (IV) administered dose levels and 1 subcutaneously (SC) administered dose level of AZD1163. Part 2 will contain 2 SC dose levels of AZD1163. A sentinel dosing approach will be taken. Each participant will be involved in the study for approximately 70 weeks.
The study will comprise of:
- A Screening Period of maximum 28 days for both Part 1 and Part 2.
- Part 1: A single dose of AZD1163 with an in-clinic period of 7 to 8 days.
- Part 2: Two doses of AZD1163, given 2 weeks apart both with an in-clinic period of 7 to 8 days.
- An outpatient Follow-up Period of approximately 15 months.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Healthy male and female participants with suitable veins for cannulation or repeated venipuncture
- •All females must have a negative pregnancy test
- •Females of childbearing potential must not be lactating and, if heterosexually active, agree to taking approved method/s of contraception
- •BMI between 18 and 32 kg/m^2 and weigh at least 45 kg
排除标准
- •Has received another new chemical entity
- •History of any disease or disorder which may put participant at risk in the study
- •Current or recurrent disease of clinical significance
- •Medical history of malignancies except for cervical carcinoma and non-melanoma skin cancer (NMSC)
- •Any clinically important illness, medical/procedure, or trauma
- •Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis result at screening
- •Any positive result on screening for serum hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HbcAb), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV)
- •History of latent or active tuberculosis (TB) or exposure to endemic areas
- •Evidence of active TB or untreated/inadequately/inappropriately treated for latent TB
- •Positive testing for Covid-19 prior to dosing, case of Covid-19 within 4 weeks, or long-term Covid-19-related sequelae
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing or presence of fever
- •Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead electrocardiogram (ECG), and any clinically important abnormalities in the 12-lead ECG
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity
研究组 & 干预措施
Part 1 Cohort 1 SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 2 SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 3 SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 4 SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 5a SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 5b SAD
Participants will receive SC injection of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 6 SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 7 SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Cohort 8 SAD
Participants will receive IV infusion of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Pooled Placebo SAD IV
Participants will receive matching IV infusion of placebo on Day 1.
干预措施: Placebo (Other)
Part 1 Placebo SAD SC
Participants will receive matching SC injection of placebo on Day 1.
干预措施: Placebo (Other)
Part 1 Cohort 9 SAD (Chinese Participants)
Participants will receive SC injection of AZD1163 on Day 1.
干预措施: AZD1163 (Biological)
Part 1 Placebo SAD (Chinese Participants)
Participants will receive matching SC injection of placebo on Day 1.
干预措施: Placebo (Other)
Part 2 Cohort 1 MAD (Global)
Participants will receive SC injection of AZD1163 on Days 1 and 15.
干预措施: AZD1163 (Biological)
Part 2 Cohort 2 MAD (Global)
Participants will receive SC injection of AZD1163 on Days 1 and 15.
干预措施: AZD1163 (Biological)
Part 2 Placebo MAD (Global)
Participants will receive matching SC injection of placebo on Days 1 and 15.
干预措施: Placebo (Other)
Part 2 Cohort 3 MAD (Chinese Participants)
Participants will receive SC injection of AZD1163 on Days 1 and 15.
干预措施: AZD1163 (Biological)
Part 2 Cohort 4 MAD (Japanese participants)
Participants will receive SC injection of AZD1163 on Days 1 and 15.
干预措施: AZD1163 (Biological)
Part 2 Placebo MAD (Chinese participants)
Participants will receive matching SC injection of placebo on Days 1 and 15.
干预措施: Placebo (Other)
Part 2 Placebo MAD (Japanese participants)
Participants will receive matching SC injection of placebo on Days 1 and 15.
干预措施: Placebo (Other)
结局指标
主要结局
Number of participants with adverse events (AEs)
时间窗: From Day -1 until end of study (Day 450)
To assess the safety and tolerability of single and multiple ascending doses of AZD1163 following IV or SC administration.
次要结局
- Area under plasma concentration-time curve from zero extrapolated to infinity (AUCinf)(Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450)
- Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)(Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450)
- Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450)
- Volume of distribution (apparent) at steady state following extravascular administration (Vz/F)(Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450)
- Maximum observed plasma (peak) drug concentration (Cmax)(Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450)
- Number of participants with positive anti-AZD1163 antibodies(Part 1: Day 1, 11, 29, 113, 225, 281, 365, 450; Part 2: Day 1, 15, 29, 57, 113, 281, 365, 450)