A Dose-Finding and Longitudinal Biomarker Study of Rhinovirus Challenge in Healthy Volunteers and Mild-Moderate Asthmatics to Evaluate the Safety and Use of a Human Rhinovirus Preparation in Developing High Dimensionality Phenotypes ("Handprints") for Asthma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 59
- 主要终点
- Number of Healthy and Asthmatic Participants With Events of Clinical Interest (ECI) (Part 1)
研究概览
简要总结
The purpose of this study is to establish the safety and tolerability of Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) human rhinovirus 16 (RV16UB) in healthy and asthmatic participants, and to identify an appropriate dosage of RV16UB in order to study biomarkers in asthmatic participants. The study is divided into 2 parts. Part 1 is a dose-finding study where healthy participants, and asthmatic participants, who were either treated or not treated with a class of long-acting beta antagonists (LABA) will be recruited to undergo nasal challenge with increasing doses of RV16UB. Part 2 is a biomarker study where mild to moderate asthmatics undergo challenge with the most appropriate dose of RV16UB identified in Part 1, based on tolerability and viral effects. .
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
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
- •Parts 1 and 2:
- •have a Body Mass Index (BMI) between =< 35 kg/m^2 and > 17 kg/m^2
- •female of childbearing potential is not pregnant and agrees to use 2 acceptable methods of birth control until 10 days after the last visit,; or female is of non-childbearing potential
- •is a non-smoker, or has not smoked within prior 12 months, with a history of =< 10 pack-years
- •Either of the following:
- •healthy (may have out-of season seasonal allergies)
- •mild to moderate-asthmatic with a history of spontaneous or exertional wheezing; and with all of the following for > 4 weeks prior: daytime symptoms twice weekly or less, no activity limitation, no nocturnal symptoms, uses reliever treatment twice daily or less, with an unchanged asthma medication dose, and uses inhaled corticosteroid (ICS) at a stable dose-equivalent of =< 500 mcg/day fluticasone propionate
- •mild to moderate-asthmatics only with a history of spontaneous or exertional wheezing; and with all of the following for > 4 weeks prior: daytime symptoms twice weekly or less, no activity limitation, no nocturnal symptoms, uses reliever treatment twice daily or less, with an unchanged asthma medication dose, and uses ICS at a stable dose-equivalent of =< 500 mcg/day fluticasone propionate
- •had a mild change in symptoms associated with viral syndrome, leading to temporarily increased short acting beta agonist use or increased ICS dose within the past 5 years
排除标准
- •has a history of severe or difficult to manage allergies (e.g. food, drug, latex)
- •has a history of asthma-related ventilatory failure in adolescence or adulthood
- •is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
- •has significant nasal septum deviation, nasal polyps or other nasal anatomical abnormality
- •shares the same household or has intimate contact with an infant, pregnant or lactating woman, or immunosuppressed individual
- •has a history or current evidence of any upper or lower respiratory tract infection within 6 weeks prior to baseline assessment
- •had major surgery or lost 1 unit (500 mL) of blood within prior 4 weeks
- •has participated in another investigational trial within the prior 10 weeks
- •is pregnant or a nursing mother
- •uses excluded prescription or non-prescription medications within 2 weeks prior to initial viral challenge and throughout the trial
研究组 & 干预措施
Healthy 10 TCID50 (Part 1)
Healthy participants were treated with 10 Tissue Culture Infective Dose 50 (TCID50) administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: RV16UB (Biological)
Healthy 100 TCID50 (Part 1)
Healthy participants were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: RV16UB (Biological)
Healthy 1000 TCID50 (Part 1)
Healthy participants were treated with 1000 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: RV16UB (Biological)
Asthmatic non-LABA 10 TCID50 (Part 1)
Participants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 10 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: RV16UB (Biological)
Asthmatic non-LABA 100 TCID50 (Part 1)
Participants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: RV16UB (Biological)
Asthmatic LABA 100 TCID50 (Part 1)
Participants with mild to moderate asthma, concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: RV16UB (Biological)
Asthmatic LABA 100 TCID50 (Part 1)
Participants with mild to moderate asthma, concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: LABA (Drug)
Asthmatic non-LABA 100 TCID50 (Part 2)
Participants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
干预措施: RV16UB (Biological)
结局指标
主要结局
Number of Healthy and Asthmatic Participants With Events of Clinical Interest (ECI) (Part 1)
时间窗: Up to Day 24
ECI are selected non-serious and serious adverse events which include the following: an overdose of Sponsor's product; requirement for systemic steroids to treat asthma exacerbation related to virus challenge; acute reaction to virus challenge, confirmed through repeat measurement and when considered potentially associated with administration of virus; specified vital sign findings within 4hr of challenge; specified symptom findings within 24hr of challenge; \>20% decrease in Forced Expiratory Volume in 1 second (FEV1) relative to baseline within 4hr of challenge; dyspnea associated with drop in FEV1 (within 4hr of challenge) that is unresponsive to a bronchodilator rescue agent within 20 minutes; Grade 2+ deviation from normal values of liver-related laboratory parameters at any time between challenge and day 14.
Number of Asthmatic Participants Demonstrating at Least 10^3 Copies/ml of Viral RNA in Nasal Lavage Fluid on Days 1 to 14 (Part 1)
时间窗: Days 1 - 14
Viral RNA was measured by real time reverse transcriptase polymerase chain reaction (qRT-PCR) from nasal lavage fluid collected on day 3 and day 7 from asthmatic participants, and the number of participants with at least 10\^3 copies/ml was determined.
Number of Participants With Serious Adverse Events (SAE) (Parts 1 and 2)
时间窗: Up to Day 24
A SAE is any adverse event occurring at any dose or during any use of the Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing in-patient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event.
Number of Asthmatic Participants Treated With a Viral Dose of 100 TCID50 With Challenge Induced Upper Airway Symptoms (Part 1)
时间窗: Day 1 up to Day 7
Asthmatic participants from Part 1 were treated with RV16UB virus at a dose of 100 TCID50, and challenge induced upper airway symptoms were monitored with a diary recording Jackson Cold Symptom Score (CSS). The CSS measures 8 cold symptoms, with each symptom scored from 0 (absent) to 3 (severe). The total score ranges from 0-24, with higher scores reflecting greater severity. The number of participants with a CSS score equal or greater than 3 for two days in a row are presented.
Time -Weighted Average (TWA) Percent Change From Baseline (CFB) in Morning FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
时间窗: Baseline and Days 1 - 7
Log-transformed FEV1 data were fit by Bayesian hierarchical longitudinal models, with a random participant effect and a fixed categorical effect for day. All baseline (day -7 to day -1) FEV1 were assumed to be with equal mean. FEV1 assessments obtained between 3 am to 3 pm were counted as morning measurements. The TWA CFB morning FEV1 on days 1-7 was calculated as the difference of the mean of estimated day 1-7 morning FEV1 value and the corresponding estimated baseline value. The 95% Confidence Interval actually refers to a 95% Credible Interval. The anticipated mean reduction from baseline is 10%.
TWA Percent CFB in Evening FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
时间窗: Baseline and Days 1- 7
Log-transformed FEV1 data were fit by Bayesian hierarchical longitudinal models, with a random participant effect and a fixed categorical effect for day. All baseline (day -7 to day -1) FEV1 were assumed to be with equal mean. FEV1 assessments obtained between 3 pm to next day 3 am were counted as evening measurements. The TWA CFB evening FEV1 on days 1-7 was calculated as the difference of the mean of estimated day 1-7 evening FEV1 value and the corresponding estimated baseline value. The FEV1 readings on the evenings of sputum inductions were excluded from the analyses. The 95% Confidence Interval actually refers to a 95% Credible Interval. The anticipated mean reduction from baseline is 10%.
Change From Baseline in Mean Maximum Jackson Cold Symptom Score (CSS) on Days 1 to 14 in Asthmatic Participants (Part 1)
时间窗: Baseline and Days 1 - 14
Asthmatic participants from Part 1 were treated with RV16UB virus, and challenge induced upper airway symptoms were monitored with a diary recording CSS. The CSS measures 8 cold symptoms, with each symptom scored from 0 (absent) to 3 (severe). The total score ranges from 0-24, with higher scores reflecting greater severity, and a positive change from baseline indicating worsening symptoms.
次要结局
- Mean Percent Change From Baseline in Maximum Drop FEV1 of Asthmatic Participants (Part 2)(Baseline and up to day 7)
- Mean Change From Baseline in TWA Asthma Control Diary (ACD) Score of Asthmatic Participants on Days 3 to 10 (Part 2)(Baseline and Days 3 to 10)