A Two-part Randomized, Double-blind Placebo Controlled Trial to Assess the Safety and Tolerability of Single and Repeat Ascending Intranasal Doses of RIG-101 in Healthy Participants Followed by Repeat Daily Administration in Adult Participants With Asthma [Part A] Followed by a Randomized Double-blind Placebo Controlled Part to Assess the Efficacy and Safety of RIG-101 in Adult Participants With Asthma Before and After Viral Challenge With Human Rhinovirus RV-A16 [Part B].
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 82
- 试验地点
- 3
- 主要终点
- Systolic/Diastolic blood pressure
研究概览
简要总结
Nested Phase 1-2 Trial of RIG-101 in Healthy and Asthmatic Participants Assessing Safety, Tolerability and Viral Challenge Efficacy
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must meet all the following inclusion criteria to be eligible to participate in the trial.
- •Participants must have a written informed consent obtained prior to any trial related procedure
- •Male and female participants aged between 18 to 65 years inclusive, at the time of informed consent.
- •Participants must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory assessments at the time of screening, as judged by the Investigator.
- •Additional Inclusion Criteria for Healthy Participants
- •- Participants must have a pre-bronchodilator FEV1 ≥80% predicted (using GLI Global predicted values17) and an FEV1 / FVC ratio of >70% absolute at screening.
- •Additional Inclusion Criteria for Participants with Asthma
- •Participants must have a clinical diagnosis of asthma.
- •Participants must have either a positive skin prick test with a wheal diameter of ≥3mm greater than control test at 15 minutes, and/or a blood eosinophil count of > 200 cells / µL and/or a FeNO level of > 25 ppb at screening.
- •Participants must have a pre-bronchodilator FEV1 ≥65% predicted at screening
- •Participants must be using SABA alone or inhaled corticosteroids (ICS) with SABA or ICS with formoterol as reliever therapy, AND/OR regular use of low to mid-dose ICS with or without LABA at a stable dose for at least 3 months prior to randomization to control their asthma.
- •Part B only
- •Participants must have an ACQ-6 score of > 0.75 at screening.
- •Participants must have a history of asthma worsening in the previous 2 years, in response to a cold or respiratory infection, as confirmed by the participant.
- •Participants must demonstrate seronegativity to RV-A16
排除标准
- •Exclusion Criteria for all Participants
- •History or presence of any clinically relevant acute or chronic medical or psychiatric condition that could interfere with the participant's safety during the clinical trial, expose the participant to undue risk or interfere with the participants ability to successfully conduct the trial, as judged by the Investigator.
- •Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the trial at time of screening.
- •Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months of the first administration of IMP and/or history of being hospitalized due to epistaxis on any previous occasion.
- •Any nasal or sinus surgery within 3 months of the first administration of IMP
- •Any signs of upper respiratory tract infection within 6 weeks of screening or prior to first administration of IMP
- •Current or previous use of tobacco, nicotine products or e-cigarettes in the past 6 months prior to screening.
- •Smoking history of > 5 pack years.
- •Additional Exclusion Criteria for Participants with Asthma
- •Any asthma exacerbation on their current asthma controller medication requiring oral/systemic corticosteroids within 8 weeks of randomization, or that resulted in overnight hospitalization requiring additional treatment for asthma within 3 months of randomization.
- •Difficult-to-treat or severe asthma requiring the maintenance use of add-on biologic Type 2 targeted treatments including anti-Immunoglobulin E, anti-IL4 receptor, anti-IL5, anti-IL5 receptor, and anti-Thymic Stromal Lymphopoietin
- •History of life-threatening asthma, defined as any asthma episode that required admission to a high-dependency or intensive therapy unit.
- •Individuals with close contact to at risk patient groups
研究组 & 干预措施
RIG-101
干预措施: RIG-101 (Drug)
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Systolic/Diastolic blood pressure
时间窗: Day 0 - 35
Systolic/Diastolic blood pressure will be measured after participants rest in a supine position for ≥5 minutes. Unit of Measure: Change from baseline mmHg
Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Day 1-35
All adverse events (AEs) and serious adverse events (SAEs) will be collected using standard regulatory AE/SAE monitoring procedures. Events will be assessed for severity and relationship to intranasal RIG-101 according to protocol-defined criteria. Data will be recorded from the signing of informed consent through the follow-up visit.
Physical examinations
时间窗: Day 0 -35
Physical examinations-general and system-specific (cardiovascular, respiratory, ENT, lymphatic, neurological, abdominal, musculoskeletal, dermatologic)-will be performed per protocol. Findings will be categorized as normal or abnormal, with clinical significance determined by the investigator. Unit of Measure: Incidence of clinically significant physical exam abnormalities
Nasal examinations
时间窗: Day 0 - 35
Nasal examinations are performed to identify structural anomalies, inflammation, or other abnormalities in the anterior nares. Unit of Measure: Incidence of nasal exam abnormalities
Spirometry (FEV₁ and FVC)
时间窗: Day 0-35
Spirometry (FEV₁ and FVC) will be conducted per ATS/ERS 2019 standards. Predicted values will use the GLI global dataset. Unit of Measure: Change from baseline in litres Measurement Tool: ATS/ERS-compliant spirometers
Triplicate 12-lead ECGs and single 12-lead ECGs
时间窗: Day 0 - 35
Triplicate 12-lead ECGs and single 12-lead ECGs will be collected after ≥5 minutes of supine rest. Parameters include HR, PR interval, QRS duration, QT, and QTcF. Unit of Measure: Change from baseline in ECG parameters
Safety laboratory testing-haematology
时间窗: Day 0 - 35
Safety laboratory testing-haematology, will be assessed per protocol and judged for clinical significance. Unit of Measure: Change in parameters of haematology laboratory values assessed using local lab reference ranges
Safety laboratory testing-Serum Chemistry
时间窗: Day 0- 35
Safety laboratory testing-Serum chemistry, will be assessed per protocol and judged for clinical significance. Unit of Measure: Change in parameters of Serum chemistry laboratory values assessed using local lab reference ranges
Safety laboratory testing-Coagulation
时间窗: Day 0 -35
Safety laboratory testing-Coagulation will be assessed per protocol and judged for clinical significance. Unit of Measure: Change in parameters of Coagulation laboratory values assessed using local lab reference ranges
Lower respiratory tract symptom score assessments
时间窗: Day -7 to 35
Participants complete twice-daily LRSS assessments for 35 days. The primary endpoint is the total symptom burden expressed as area under the curve (AUC) for LRSS from baseline through Day 35. Unit of Measure: AUC (LRSS × days) Measurement Tool: Twice-daily electronic diary (eDiary) symptom scoring system
AUC of Lower respiratory tract symptom score
时间窗: Day -7 to 35
AUC of LRSS where the lower respiratory symptoms are measured for 35 days by twice-daily date and time stamped eDiary collection
Vital Signs - heart rate
时间窗: Day 0 - 35
Heart rate will be measured after participants rest in a supine position for ≥5 minutes. Unit of Measure: Change from baseline BPM
次要结局
未报告次要终点