A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Assess the Safety, Tolerability, PD and PK of RLS-0071 in Healthy Adult Subjects After Challenge With Inhaled Lipopolysaccharide (LPS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change from Baseline in absolute neutrophil count in induced sputum
研究概览
简要总结
This is a Phase 1b, randomized, double-blind, placebo-controlled, dose range finding study to assess the safety, tolerability, pharmacodynamics (PK) and pharmacokinetics (PD) of RLS-0071 in healthy adult subjects after challenge with inhaled lipopolysaccharide (LPS).
Clinical data are required to determine the potential benefit of RLS-0071, a novel drug that specifically inhibits multiple inflammatory pathways, for the treatment of severe asthma. This study has been designed to evaluate the efficacy of IV administered RLS-0071 to reduce inflammation symptoms in healthy subjects challenged with inhaled LPS, a well-known agent that produces a safe and well-controlled inflammatory response in the lung. This is a critical proof-of-concept study and dose-optimization study for future studies in severe asthma patients.
A total of 48 healthy adult subjects are planned to be enrolled in this study. Subjects will be randomly allocated to either of the treatment arms (Arm A or Arm B) with RLS-0071 or the placebo arm (Arm C) in a 1:1:1 ratio. Subjects will either receive intravenous infusion of RLS-0071 at a lower dose every 8 hours for a total of 3 doses (Arm A), RLS-0071 at a higher dose every 8 hours for a total of 3 doses (Arm B) or placebo dosed every 8 hours for a total of 3 doses (Arm C). Each subject completing the study will be evaluated for up to a total of 7 days. Subjects will be permitted to participate in only 1 arm of the study. Subjects discontinuing the study before data was collected at 6 hours post LPS challenge will be considered dropouts and will be replaced.
详细描述
The inclusion of a double-blind design allows a comparison between subjects receiving RLS-0071 and placebo subjects who are experiencing the same procedures and restrictions in an unbiased manner. The inclusion of a placebo control group will facilitate the distinction between efficacy signals and possible procedural/environmental events.
Eligibility criteria have been included to mitigate the risk to study subjects. Vulnerable populations such as children are excluded, as well as subjects whose medical history suggest a higher risk of experiencing adverse effects.
LPS inhalation is used in this study to be able to evaluate proof-of-concept efficacy of RLS-0071 in otherwise healthy subjects. Thus, PD assessments will be conducted to provide evidence of target engagement and guide the design of future severe asthma studies.
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)
盲法说明
During the entire study, subjects, Investigators, the Sponsor, and all other persons involved in the conduct of the study will be blinded to treatment.
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
- 未提供
排除标准
- •Use of any prescription or over-the-counter (OTC) medications, herbal products (eg, cannabidiol, St John's Wort, milk thistle), or supplements/vitamins within 14 days or 5 half-lives (whichever is longer) before first dosing with IMP and for the duration of the study, with the exception of those approved by the Investigator and Sponsor (eg, oral contraceptives, hormone replacement therapy, acetaminophen for pain relief).
- •Receipt of any investigational agent or treatment within 30 days or 5 half-lives, whichever is longer, before first dosing with IMP, or concurrent participation in another clinical study.
- •Receipt of any protein- or antibody-based therapeutic agents (eg, growth hormones or monoclonal antibodies) within 3 months before first dosing with IMP.
- •Note: Influenza and COVID-19 vaccines will be allowed if all doses in the regimen have been administered more than 21 days before first dosing with IMP.
- •History of any major surgery within 6 months before first dosing with IMP.
- •Prior diagnosis of COVID 19 within 90 days before first dosing with IMP.
- •History of hepatic disease, or current clinically significant liver function test results, defined as ALT, AST, total bilirubin and fractionated bilirubin, or alkaline phosphatase > 1.5 × upper limit of normal (ULN) at Screening.
- •Note: Isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated, and direct bilirubin is < 35%.
- •History of any clinically relevant or chronic psychiatric, renal, hepatic, pancreatic, cardiovascular, neurological, hematological, or gastrointestinal abnormality (eg, inflammatory bowel disease)
- •History of severe allergic/anaphylactic reaction
- •History of autoimmune disease including glomerulonephritis
- •Known hypersensitivity to the active substance or to any of the excipients of each IMP including lipopolysaccharide (LPS) and polyethylene glycol (PEG)
- •History of any active infection within 14 days before dosing with IMP, if deemed clinically significant by the Investigator and Sponsor
- •Any acute illness within 30 days before dosing with IMP
- •Lower respiratory tract infection within 3 months before first dosing with IMP
- •History of warfarin use or International Normalized Ratio ≥ 1.5
- •History (within 2 years before the first dosing with IMP) of moderate or severe use disorder for any substance other than caffeine (based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria)
- •Known diagnosis or active infection with Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV)-1 or HIV-2
- •Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of RLS-0071
- •Presence of clinically significant ECG finding (confirmed upon repeat testing) that, in the opinion of the Investigator and/or Sponsor, may interfere with any aspect of study conduct or interpretation of results
- •Concurrent conditions that could interfere with safety and/or tolerability measurements, as determined by the Investigator
- •Pregnant and/or lactating
- •Inability to produce sufficient amounts of induced sputum at baseline visit
- •Inability to tolerate IV administration
- •Poor venous access, as determined by the Investigator
- •Unable or unwilling to cooperate with the study site staff for any reason
- •Employees of the Sponsor or subjects who are employees or relatives of the Investigator
研究组 & 干预措施
Arm A
RLS-0071 lower dose group
干预措施: RLS-0071 (10 mg/kg intravenously every 8 hours for total of 3 doses) (Drug)
Arm B
RLS-0071 higher dose group
干预措施: RLS-0071 (loading dose of 120 mg/kg followed by 40 mg/kg every 8 hours for 2 additional doses) (Drug)
Arm C
Placebo group
干预措施: Placebo (saline dosed every 8 hours for a total of 3 doses) (Drug)
结局指标
主要结局
Change from Baseline in absolute neutrophil count in induced sputum
时间窗: At 6 and 24 hours after inhaled lipopolysaccharide (LPS).
Primary PD
次要结局
- Change from Baseline in cytokines (Th1 and Th17) in induced sputum(At 6 and 24 hours after inhaled LPS.)