A Phase 1a/1b, Randomised, Double Blind, Placebo-controlled, Dose-escalating Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of RB042 Administered Via Inhalation to Healthy Adult Volunteers, Healthy Adult Smokers and Patients With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- Number and frequency of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a 4-part, randomised, double-blind, placebo-controlled, first in human study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of inhaled RB042.
详细描述
The purpose of this study is to measure the safety, tolerability, PK, and PD of inhaled RB042 compared with inhaled placebo in healthy adult volunteers, healthy adult smokers and patients with moderate to severe chronic obstructive pulmonary disease.
Study details include:
- Overall study duration of up to 19 months.
- Participants in Part A (healthy adult volunteers) will be required to visit the study site for assessments on 11 occasions, including a 4-day in-house stay, over 4 months.
- Participants in Parts B will be required to visit the study site for assessments on 13 occasions, including a 17-day (Day -1 to 16) and 3-day (Day 21 to 24) in-house stay, over 5 months.
- Participants in Part C will be required to visit the study site for assessments on 10 occasions, including in-house stays between Day -1 to 2, Day 7 to 8, Day 14 to 15, Day 21 to 23 over 5 months.
- Patients in Part D will be required to visit the study site for assessments on 10 occasions over 5 months.
- Participants will be administered a single dose (Part A) or multiple doses (Parts B, C and D) of study intervention.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part A, B, C only: Participants must be 18 to 55 years of age inclusive.
- •Part D only: Patients must be 40 to 80 years of age inclusive.
- •Part A, B, C only: Participants must be overtly healthy as determined by medical evaluation.
- •Part C only: have a ≥10 pack years smoking history, have smoked tobacco products (cigarettes, cigars, or equivalent) regularly for the past 12 months, and currently smoke daily.
- •Part D only: Former smokers (smoked a total of 100 or more cigarettes in their lifetime but has not smoked in the past 6 months to over a year).
- •Part A, B, C only: Have forced expiratory volume (FEV1) ≥80% predicted and FEV1 to FVC ratio (FEV1/FVC) ≥0.7 at Screening and on Day -
- •Part D only: Have forced expiratory volume (FEV1) between ≥30% and <80% predicted and FEV1 to FVC ratio (FEV1/FVC) <0.7 post-bronchodilation at Screening.
- •Part D only: Documented clinical diagnosis of COPD per 2026 Global Initiative for Chronic Obstructive Lung Disease (GOLD) for greater than ≥1 year and a history of chronic bronchitis as evidenced by frequent productive cough in the 2-year period immediately before Screening.
- •Part D only: Have clinically stable COPD with no moderate to severe exacerbations in the past 3 months.
- •Part D only: Must be on stable assigned maintenance COPD therapy.
- •Body weight at least 50 kg and have a body mass index (BMI) within the range 18.0 and 32.0 kg/m2 (inclusive)
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test and must not be lactating.
- •Participants must agree to use an approved method(s) of highly effective contraception as defined in the protocol.
排除标准
- •Part A, B and C only: Clinically significant history or presence of gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, neurologic, hematologic, metabolic, autoimmune, or oncologic disorders that may affect safety or study outcomes.
- •Part D only: Current unstable clinically significant history or presence of gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, neurologic, hematologic, metabolic, autoimmune, or oncologic disorders that may affect safety or study outcomes.
- •Part A, B and C only: Chronic or active respiratory disease (e.g., asthma, COPD) or history of angioedema within 3 years.
- •Part D only: Patients with other respiratory conditions other than COPD (for example, clinically significant asthma, active tuberculosis, pulmonary fibrosis) are excluded if these conditions are the primary cause of their respiratory symptoms.
- •Active or chronic liver disease, or abnormal liver function tests (ALT, AST, or bilirubin outside reference range, except Gilbert's syndrome).
- •QTcF >450 msec (males) or >470 msec (females).
- •Renal impairment (creatinine clearance <90 mL/min) or thrombocytopenia (<150 × 10⁹/L).
- •Positive test for hepatitis B surface or core antigen, hepatitis C (unless HCV-RNA negative), or HIV.
- •Active respiratory infection within 5 days before study start.
- •Recent or concurrent use of medications, herbal supplements, vaccines, or blood products that could interfere with study safety or interpretation.
- •Participation in another investigational study within 30 days, or blood donation >400 mL within 30 days.
- •Parts A, B and D only: Regular smoking (≥1 day per week) within 6 months prior to dosing, or a positive urine cotinine test at screening or Day -
- •Excessive alcohol consumption (>21 drinks/week for males or >14 for females).
- •History of severe drug reaction or anaphylaxis.
- •Part B and C only: Contraindication to, or unwillingness to undergo, bronchoscopy.
- •Any psychiatric or medical condition that, in the investigator's opinion, could compromise safety or compliance.
研究组 & 干预措施
Cohort B3
Participants will receive RB042 (Dose Level B3) or matching placebo on Days 1, 8, 15, and 22.
干预措施: RB042 (Drug)
Cohort B3
Participants will receive RB042 (Dose Level B3) or matching placebo on Days 1, 8, 15, and 22.
干预措施: Placebo inhalation solution (Drug)
Cohort C1
Participants will receive RB042 (Dose Level C1) or matching placebo on Days 1, 8, 15, and 22.
干预措施: RB042 (Drug)
Cohort C1
Participants will receive RB042 (Dose Level C1) or matching placebo on Days 1, 8, 15, and 22.
干预措施: Placebo inhalation solution (Drug)
Cohort B4
Participants will receive RB042 (Dose Level B4) or matching placebo on Days 1, 8, 15, and 22.
干预措施: RB042 (Drug)
Cohort B4
Participants will receive RB042 (Dose Level B4) or matching placebo on Days 1, 8, 15, and 22.
干预措施: Placebo inhalation solution (Drug)
Cohort D1
Participants will receive RB042 (Dose Level D1) or matching placebo on Days 1, 8, 15, and 22.
干预措施: RB042 (Drug)
Cohort D1
Participants will receive RB042 (Dose Level D1) or matching placebo on Days 1, 8, 15, and 22.
干预措施: Placebo inhalation solution (Drug)
Cohort A1
Participants will receive RB042 (Dose Level A1) or matching placebo on Day 1.
干预措施: RB042 (Drug)
Cohort A3
Participants will receive RB042 (Dose Level A3) or matching placebo on Day 1.
干预措施: RB042 (Drug)
Cohort A3
Participants will receive RB042 (Dose Level A3) or matching placebo on Day 1.
干预措施: Placebo inhalation solution (Drug)
Cohort A4
Participants will receive RB042 (Dose Level A4) or matching placebo on Day 1.
干预措施: RB042 (Drug)
Cohort A4
Participants will receive RB042 (Dose Level A4) or matching placebo on Day 1.
干预措施: Placebo inhalation solution (Drug)
Cohort B1
Participants will receive RB042 (Dose Level B1) or matching placebo on Days 1, 8, 15, and 22.
干预措施: Placebo inhalation solution (Drug)
Cohort B1
Participants will receive RB042 (Dose Level B1) or matching placebo on Days 1, 8, 15, and 22.
干预措施: RB042 (Drug)
Cohort A1
Participants will receive RB042 (Dose Level A1) or matching placebo on Day 1.
干预措施: Placebo inhalation solution (Drug)
Cohort A2
Participants will receive RB042 (Dose Level A2) or matching placebo on Day 1.
干预措施: RB042 (Drug)
Cohort A2
Participants will receive RB042 (Dose Level A2) or matching placebo on Day 1.
干预措施: Placebo inhalation solution (Drug)
Cohort B2
Participants will receive RB042 (Dose Level B2) or matching placebo on Days 1, 8, 15, and 22.
干预措施: Placebo inhalation solution (Drug)
Cohort B2
Participants will receive RB042 (Dose Level B2) or matching placebo on Days 1, 8, 15, and 22.
干预措施: RB042 (Drug)
结局指标
主要结局
Number and frequency of treatment-emergent adverse events (TEAEs)
时间窗: From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts B and D)
To assess the safety and tolerability of single and multiple doses of RB042 when administered via a nebuliser to healthy adult volunteers, healthy adult smokers and patients with moderate to severe stable COPD.
Number and frequency of treatment-emergent adverse events (TEAEs)
时间窗: From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B)
To assess the safety and tolerability of single and multiple doses of RB042 when administered via a nebuliser to healthy adult volunteers and healthy adult smokers
次要结局
- Trough concentration(On Days 7, 14, and 21)
- Maximum concentration (Cmax)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts B and D))
- Time to maximum concentration (Tmax)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts B and D))
- Terminal elimination half-life (t½)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts B and D))
- Area under the concentration-time curve (AUC)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts B and D))
- Time to maximum concentration (Tmax)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B))
- Terminal elimination half-life (t½)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B))
- Area under the concentration-time curve (AUC)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B))
- Maximum concentration (Cmax)(From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B))