A Phase I, Randomised, Double-blind, Placebo-controlled, Single Ascending Dose Study of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of Subcutaneous AZD6912 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events (AEs)
研究概览
简要总结
This study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses of AZD6912 administered subcutaneously (SC) in healthy participants.
详细描述
In this First-In-Human (FiH) study, eligible participants will be randomly assigned to 6 cohorts in a 3:1 ratio to receive either a single dose of AZD6912 SC or placebo. The first 2 participants in each cohort will be dosed as a sentinel pair, with one receiving AZD6912 SC and the other receiving placebo.
The study will comprise of, a screening period of 70 days, a treatment period where participants will stay at the Clinical Unit from the day before study intervention administration until at least 240 hours and will be discharged on Day 11. Outpatient visits would start weekly from Day 15, then bi-weekly from Day 43, 4-weekly from Day 99, and 6-weekly from Day 155, with additional follow-up visits approximately every 4 weeks as needed until complement activity returns to the normal range.
The study will last approximately 25 months, including the optional Japanese cohorts, with each participant participating for about 38 weeks or longer until complement activity returns to normal range (per local laboratory).
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Females must have a negative pregnancy test.
- •Contraceptive use by males and females should be consistent with local regulations.
- •Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg.
- •For optional Japanese participants only:
- •Participants must be of Japanese descent defined as: first generation (born to 2 Japanese parents and 4 Japanese grandparents).
- •Born in Japan, and not have lived outside Japan for more than 5 years.
- •Lifestyle, including diet, must not have significantly changed since leaving Japan.
排除标准
- •History of any clinically important disease or disorder.
- •Current or recurrent disease of clinical significance that could affect clinical assessments or clinical laboratory evaluations.
- •Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.
- •History of congenital or acquired immunodeficiency or complement deficiency or an underlying condition that predisposes to infection.
- •History of any Neisseria infection, unexplained, recurrent infections, or infection requiring treatment with systemic antibiotics.
- •Evidence of hepatitis B infection (positive for HBsAg or positive for anti-HBcAb) or hepatitis C viral infection (HCV Abs or hepatitis C RNA positive) or HIV infection (positive for HIV type 1 or type 2 Abs).
- •Participants testing positive for COVID-19 prior to dosing.
- •Any cardiac abnormalities.
- •A CAP activity < 60% at screening.
- •Known or suspected history of drug abuse, history of alcohol abuse or smoking.
研究组 & 干预措施
AZD6912 Dose 1
Participants will receive AZD6912 Dose 1.
干预措施: AZD6912 (Drug)
AZD6912 Dose 2
Participants will receive AZD6912 Dose 2.
干预措施: AZD6912 (Drug)
AZD6912 Dose 3
Participants will receive AZD6912 Dose 3.
干预措施: AZD6912 (Drug)
AZD6912 Dose 4
Participants will receive AZD6912 Dose 4.
干预措施: AZD6912 (Drug)
AZD6912 Dose 5
Participants will receive AZD6912 Dose 5.
干预措施: AZD6912 (Drug)
AZD6912 Dose 6
Participants will receive AZD6912 Dose 6.
干预措施: AZD6912 (Drug)
Placebo
Participants will receive Placebo.
干预措施: Placebo (Drug)
AZD6912 additional Japanese cohort 1
Participants will receive AZD6912.
干预措施: AZD6912 (Drug)
AZD6912 additional Japanese cohort 2
Participants will receive AZD6912.
干预措施: AZD6912 (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs)
时间窗: From screening (Day -70) to last follow up visit (Day 197- approximately 38 weeks)
To assess the safety and tolerability of AZD6912 in healthy participants.
次要结局
- Area under plasma concentration-time curve from zero to infinity (AUCinf) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Time of last measurable concentration (tlast) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Dose normalised Cmax (Cmax/D) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Dose normalised AUClast (AUClast/D) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Percent change from baseline in serum of Complement functional activity (CAP)(From randomization to Day 197 (up to 28 weeks))
- Terminal elimination half-life (t½λz) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Maximum observed plasma (peak) drug concentration (Cmax) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Dose normalised AUCinf (AUCinf/D) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD6912(From randomization to Day 197 (up to 28 weeks))
- Percent change from baseline in plasma concentrations of Complement factor B (CFB) protein(From randomization to Day 197 (up to 28 weeks))