A Phase 1 Study to Examine the Cytokine Levels, Gene Expression and Safety of a Single Nasal Dose of JNJ-43260295, in a Double-Blind, Randomized, Placebo-Controlled Setting in Healthy Subjects, and by an Open-Label Assessment in Atopic Subjects With Mild to Mild-Persistent Asthma With and Without Nasal Allergen Challenge Prior to Dosing
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 主要终点
- Cytokine Levels in Nasal Lavage
研究概览
简要总结
The purpose of this study is to investigate the cytokine levels in nasal lavage and gene expression in nasal scraping following a single nasal dose of JNJ-43260295 in healthy participants, and in atopic mild to mild-persistent asthmatic (breathing disorder in which there is wheezing and difficulty in breathing) participants with and without nasal allergen challenge prior to dosing.
详细描述
This study consists of 2 parts. In first part, healthy adult participants will receive a single nasal dose of JNJ-43260295 or placebo in a double blind (both the participant and investigator do not know whether participant is assigned to receive study medication or placebo), randomized (study medication or placebo assigned to participants by chance), and placebo-controlled (study in which the experimental treatment or procedure is compared to a placebo) setting. In second part, which will be open label (participants and investigators are aware about the treatment, participants are receiving), atopic participants with mild to mild-persistent asthma will participate in 3 consecutive treatment periods (Period 1, 2, and 3). In Period 1, each participant will receive a single nasal dose of JNJ-43260295 without prior nasal allergen challenge. In Period 2, each participant will receive a single nasal dose of JNJ-43260295, preceded by a nasal allergen challenge approximately 15 hours prior to the JNJ-43260295 dosing. In Period 3, each participant will receive single nasal allergen challenge without JNJ-43260295. There will be a washout period of at least 21 days between 3 consecutive treatment periods. Cytokine levels in nasal lavage and gene expression in nasal scraping will be primarily evaluated during all treatment periods. Participants' safety will be monitored throughout the study.
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)
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
- •A. Healthy Participants and Atopic Mild to Mild-Persistent Asthmatic Participants:
- •Participants must be non-smokers or non-regular smokers (1 to 2 cigarettes on the weekend as part of social gathering) for at least 3 months prior to Screening, according to the participant's self-reported medical history. Participants should be willing to (continue to) abstain from smoking from Screening until completion of the last study related activity
- •Participants must have a body mass index (BMI: weight in kilogram [kg] divided by the height in square meter [m^2]) of 18.0 to 30.0 kg/m^2, extremes included
- •Participants must have a normal 12-lead electrocardiogram (ECG) at Screening including normal sinus rhythm (heart rate between 40 and 100 beats per minute [bpm]); QT interval corrected for heart rate according to Fridericia (QTcF) interval less than and equal to (<=) 450 milliseconds (ms); QRS interval lower than 120 ms; and PR interval <=220 ms
- •Participants must be healthy, with the exception of findings related to asthma and allergy in atopic mild to mild-Persistent asthmatic participants, on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs (Systolic Blood Pressure [BP], Diastolic BP, pulse rate, respiratory rate, and body temperature), and the results of blood biochemistry and hematology tests performed at Screening
- •Participants must be willing/ able to adhere to the prohibitions and restrictions specified in the protocol and study procedures
- •B. Atopic Mild to Mild-Persistent Asthmatic Participants:
- •Participants with Investigator-diagnosed mild to mild-persistent asthma based on the Guidelines for the Diagnosis and Management of Asthma
- •Participants having a well-established allergen profile (participants have been previously skin tested and, by history, have allergic responses to specific allergens)
- •Participants with forced expiratory volume in 1 second (FEV1) greater than (>) 70 percent (%) of predicted at Baseline
排除标准
- •A. Healthy Participants and Atopic Mild to Mild-Persistent Asthmatic Participants:
- •Participants having a significant (by the assessment of the Investigator) nasal abnormality and/or has a history of nasal or sinus surgery within 12 months of enrollment
- •Participants having an upper or lower respiratory tract infection within 4 weeks of enrollment
- •Participants with a history or evidence of use of alcohol, barbiturates, amphetamines, recreational or narcotic drug use within the past 1 year, which in the Investigator's opinion would compromise participant's safety and/or compliance with the study procedures
- •Participants with a known history of human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection, or with a known history of hepatitis A, B, or C virus infection at study Screening
- •Female participants who are breastfeeding at Screening or having a positive urine pregnancy test at Screening
- •B. Atopic Mild to Mild-Persistent Asthmatic Participants:
- •Hospitalization or treatment in an emergency care facility for asthma during the last 3 years
- •Participants using nasal corticosteroids on a daily basis in the 4 weeks prior to enrollment
- •Participants who have received allergen immunotherapy in the last 2 years
研究组 & 干预措施
JNJ-43260295 (Healthy Participants)
Participants will receive a single nasal dose of JNJ-43260295, 6400 microgram, equally spread over the two nostrils.
干预措施: JNJ-43260295 (Drug)
Placebo (Healthy Participants)
Participants will receive a single nasal dose of placebo matching to JNJ-43260295.
干预措施: Placebo (Drug)
JNJ-43260295 (Asthmatic Participants)
Participants will participate in 3 consecutive treatment periods (Periods 1, 2, and 3). In Period 1, each participant will receive a single nasal dose of JNJ-43260295 without prior nasal allergen challenge. In Period 2, each participant will receive a single nasal dose of JNJ-43260295, preceded by a nasal allergen challenge approximately 15 hours prior to the dosing. In Period 3, each participant will receive single nasal allergen challenge without JNJ-43260295. There will be a washout period of at least 21 days between 3 consecutive treatment periods.
干预措施: JNJ-43260295 (Drug)
JNJ-43260295 (Asthmatic Participants)
Participants will participate in 3 consecutive treatment periods (Periods 1, 2, and 3). In Period 1, each participant will receive a single nasal dose of JNJ-43260295 without prior nasal allergen challenge. In Period 2, each participant will receive a single nasal dose of JNJ-43260295, preceded by a nasal allergen challenge approximately 15 hours prior to the dosing. In Period 3, each participant will receive single nasal allergen challenge without JNJ-43260295. There will be a washout period of at least 21 days between 3 consecutive treatment periods.
干预措施: Nasal Allergen Challenge (Drug)
结局指标
主要结局
Cytokine Levels in Nasal Lavage
时间窗: Up to 48 hours post dose
Sixteen cytokines will be assessed: interferon alpha (IFN-alpha), IFN-beta, IFN-gamma, IFN-lambda, interleukin-1 alpha (IL-1 alpha), IL-4, IL-5, IL-6, IL 8, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-23, and tumor necrosis factor-alpha (TNF-alpha), using the 16-plex kit.
Gene Expression in Nasal Scrapings
时间窗: Up to 48 hours post dose
Gene expression will be determined by analyzing total ribonucleic acid (RNA) by microarray chips.
次要结局
- Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)(AEs: Baseline up to 8 days after the last dose of study drug; SAEs: Baseline up to 30 days after the last dose of study drug)