A Study in Two Parts: (Phase 1) A Randomized, Double-blinded, Placebo--controlled, Single-ascending-dose Study in Healthy Adult Subjects and (Phase 1b) an Open-label, Nested, Divided-dose Study in Adults With Cystic Fibrosis to Assess the Safety, Tolerability, and Pharmacokinetics of ARCT-032
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Incidence, severity and dose-relationship of AEs
研究概览
简要总结
Determine the safety, tolerability and pharmacokinetics of single doses of ARCT-032 in healthy adult subjects (Phase 1) and of two doses in Adults with Cystic Fibrosis (Phase 1b).
详细描述
Phase 1 of this study is a single ascending dose, first-in-human study to determine the safety, tolerability, and pharmacokinetics (PK) of ARCT-032. After screening, healthy adult participants will be randomized 3:1 to inhale a single dose of nebulized ARCT-032 or placebo. There are 4 planned sequential dose cohorts. After dosing, participants will have follow-up assessments over a 4-week period.
Phase 1b in adults with cystic fibrosis will enroll after Phase 1 is completed and safety data are reviewed. Phase 1b is an open-label, two-dose study in adults with cystic fibrosis to assess the safety, tolerability, and pharmacokinetics of ARCT-032. After completion of screening, each participants will inhale two doses of nebulized ARCT-032 two days apart. Participants will have follow-up assessments over a 4-week period.
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
- Double (Participant, Investigator)
盲法说明
Participant and investigator masking only applies to Phase 1 healthy volunteers only. For Phase 1b, there is no masking, None (Open Label) should be applied.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Phase 1: Healthy males or females aged 18 to 65 years at the time of informed consent.
- •Phase 1b: Males or females aged 18 to 65 years with confirmed diagnosis of CF documented in subject's medical record
- •Body weight between 40-100Kg and body mass index between 16-35 kg/m2
- •Phase 1: Forced expiratory volume (FEV1) at screening >85% of predicted value for age, sex, and height.
- •Phase 1b: FEV1 at screening between 50% and 100% of predicted value
- •Surgically sterile or using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days after the last dose of study drug.
- •Phase 1b only: Subjects with CF on CFTR modulator therapy must be on a stable regimen for at least 2 months prior to screening.
排除标准
- •History of illness or condition that might pose an additional risk or may confound study results.
- •Pregnant or lactating (breast feeding)
- •History of severe allergic reaction to a liposomal product
- •Clinically significant abnormalities in Screening laboratory results
- •Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
- •Treatment with another investigational drug, biological agent, or device within 30 days of screening, or 5 half-lives of investigational drug, whichever is longer
- •Drug or alcohol abuse within the past year
- •History of moderate to heavy smoking or vaping (>10 cigarettes/sessions per day) within 6 months prior to the dose of study drug. Participants must be willing to refrain from smoking or vaping within 1 week of dosing through Day 15
- •Systemic or inhaled corticosteroids within 3 months prior to screening (Phase 1 only).
- •Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study
研究组 & 干预措施
ARCT-032, Healthy Adults
Ascending single doses of ARCT-032 administered to healthy adults via nebulizer
干预措施: ARCT-032 (Drug)
Placebo, Healthy Adults
Single doses of 0.9% Saline administered to healthy adults via nebulizer
干预措施: Placebo (Other)
ARCT-032,. Adults with Cystic Fibrosis
Two doses of ARCT-032 administered to adults with Cystic Fibrosis via nebulizer
干预措施: ARCT-032 (Drug)
结局指标
主要结局
Incidence, severity and dose-relationship of AEs
时间窗: 4 weeks
Safety and tolerability of ARCT-032 assessed by determining the incidence, severity and dose-relationship of AEs by dose
次要结局
- Maximum observed plasma concentration (Cmax) after single dose of ARCT-032(Up to 2 Weeks)
- Change in plasma area under the curve after single dose of ARCT-032(Up to 2 Weeks)
- T1/2 after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032(Up to 2 Weeks)
- CL after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032(Up to 2 Weeks)
- Vss after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032(Up to 2 Weeks)
- Time at which Cmax occurred after single dose of ARCT-032(Up to 2 Weeks)
- AUC0-inf after single dose (Phase 1) or two doses (Phase 1b) of ARCT-032(Up to 2 Weeks)