A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1920 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Number of participants with Adverse events (AEs)
研究概览
简要总结
This study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single ascending doses (SADs) of ALXN1920 subcutaneous (SC) and of a single dose of ALXN1920 intravenous (IV) in healthy adult participants.
详细描述
This is a first-in-human study in healthy adult participants.
Eligible participants will be randomly assigned in a 3:1 (ALXN1920:Placebo) ratio in each of the treatment cohorts. The first 2 participants randomized to each cohort will be dosed as a sentinel pair, with 1 participant on active treatment and 1 participant on placebo. At the discretion of the Investigator, up to 3 more participants will be added at least 48 hours after the dosing of the sentinel pair, followed by dosing of the remaining participants in the cohort no earlier than 72 hours after sentinel pair dosing.
The study will comprise:
A Screening Period of up to 28 days; A Dosing Period (single dose through to Follow-up Visit) of approximately 28 days; A Final Follow-up period and end of study Visit is planned on Day 29.
Each participant will be involved in the study for approximately 56 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 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 participants
- •Body mass index within 18.0 to 32.0 kg/m^2 (inclusive), with a minimum body weight of 50.0 kg.
- •Female participants of childbearing potential and male participants must follow protocol-specified contraception guidance.
- •For Cohort 6, participants of Japanese descent, defined as having both parents and 4 grandparents who are ethnically Japanese.
排除标准
- •Significant history or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders.
- •History of significant allergic reaction.
- •History of any Neisseria infection
- •Active systemic bacterial, viral, or fungal infection.
- •Participants who at Day -1 are either testing positive for coronavirus disease 2019 (COVID-19), or have not had at least 4 weeks elapse of recovery time (a negative test), or are experiencing long-term COVID-19-related sequelae.
- •Any major surgery within 8 weeks of Screening.
- •Known or suspected history of drug or alcohol abuse.
- •Current tobacco users or smokers.
- •Positive Human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C viral infection.
- •Female participant who are pregnant, breastfeeding, or intending to conceive during the course of the study.
研究组 & 干预措施
Cohort 2
Participants will receive a single dose of ALXN1920.
干预措施: ALXN1920 (Biological)
Cohort 3
Participants will receive a single dose of ALXN1920.
干预措施: ALXN1920 (Biological)
Cohort 4
Participants will receive a single dose of ALXN1920.
干预措施: ALXN1920 (Biological)
Cohort 1
Participants will receive a single dose of ALXN1920.
干预措施: ALXN1920 (Biological)
Cohort 5
Participants will receive a single dose of ALXN1920.
干预措施: ALXN1920 (Biological)
Cohort 6: Japanese Cohort
Japanese participants will receive a single dose of ALXN1920.
干预措施: ALXN1920 (Biological)
Pooled Placebo
Participants will receive Placebo.
干预措施: Placebo (Biological)
结局指标
主要结局
Number of participants with Adverse events (AEs)
时间窗: Up to End of study visit (Day 29)
To assess the safety and tolerability of single ascending doses of ALXN1920.
次要结局
- Amount of unchanged drug excreted in urine (Ae)(Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose))
- Area under the concentration-time curve from time 0 (dosing) to the last quantifiable concentration (AUC0-t)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Area under the concentration-time curve from time 0 (dosing) to time infinity (AUCinf)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Total body clearance (CL)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Volume of distribution (Vd)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Maximum observed concentration (Cmax)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Fraction of dose excreted in urine (fe)(Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose))
- Terminal elimination half-life (t½)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Time to maximum observed concentration (tmax)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1920(Day 1 pre-dose and Day 29 post-dose)
- Terminal-phase elimination rate constant (λz)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Apparent clearance (CL/F)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Apparent volume of distribution (Vd/F)(Day 1 (Pre-dose, 0.5, 1, 2, 6 and 12 hours post-dose), post-dose on Day 2, 3, 4, 5, 6, 8, 15, 22, and 29)
- Renal clearance (CLR)(Day 1 through Day 5 (Pre-dose and up to 96 hours post-dose))
- Change in factor H(Day 1 (Pre-dose, 0.5, 1 and 2 hours post-dose), post-dose on Day 2, 3, 4, 5, 8, 15, 22, and 29)
- Change in complement alternative pathway (CAP) activity(Day 1 (Pre-dose, 0.5, 1 and 2 hours post-dose), post-dose on Day 2, 3, 4, 5, 8, 15, 22, and 29)
- Geometric Mean Ratio (GMR) of Area Under the Curve (AUC) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1920(Day 29 post-dose)