A Phase 2a, Randomized, Double-blinded, Placebo-Controlled Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of Repeated Doses of Orally Administered JNJ 53718678 Against Respiratory Syncytial Virus Infection in the Virus Challenge Model in Healthy Adult Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 主要终点
- Area Under the Viral Load-time Curve (VL AUC)
研究概览
简要总结
The purpose of this study is to evaluate the antiviral effect of repeated oral dosing of JNJ 53718678 compared to placebo in healthy adult participants infected through inoculation with respiratory syncytial virus (RSV)-A Memphis 37b virus.
详细描述
This is a randomized (study medication assigned to participants by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled, single-center study of JNJ 53718678 in healthy adult participants. Study consists of 3 phases: Screening (Day -56 and Study Day -3 prior to the planned date of virus inoculation/challenge on Study Day 0), quarantine (includes challenge on Day -1 or -2 and treatment for 7 days), and follow-up (Day 15 and 28). Participants will be admitted to the quarantine unit on Study Day -1 or - 2 and will be inoculated (intranasal) with the RSV-A Memphis 37b virus on Study Day 0. Participants will be evaluated in 3 cohorts: Cohort 1 and Cohort 3 (participants will be dosed with JNJ-53718678 or placebo for 7 days) and Cohort 2 (for up to 7 days [Dosing Days 1-x] [x will be determined based on the results from Cohort 1]). Participants will be randomized and JNJ-53718678/placebo dosing will be started after RSV presence in nasal wash has been detected by polymerase chain reaction (PCR). After completion of Cohort 1, data will be reviewed (unblinded) and the antiviral activity, safety, pharmacokinetic, clinical symptom and mucus weight data will be evaluated, based on which Cohort 2 will be initiated. 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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female participants must be of non-childbearing potential: postmenopausal for at least 2 years or surgically sterile or otherwise incapable of becoming pregnant
- •Female participants, except for postmenopausal women, must have a negative serum pregnancy test at screening
- •Participants must agree to comply with contraceptive measures as mentioned in protocol
- •Participants must be sero-suitable for respiratory syncytial virus (RSV) within 57 days prior to inoculation
- •Participants must be non-smokers for at least one month prior to screening and participants must have a negative cotinine test at screening
排除标准
- •Participants with a past history of heart arrhythmias (extrasystoli, tachycardia at rest) or of risk factors for Torsade de Pointes syndrome
- •Participants with a history or evidence of abuse of alcohol, barbiturates, amphetamines, recreational or narcotic drug use within the past 3 months, which in the Investigator's opinion would compromise participant's safety and/or compliance with the study procedures
- •Participants with current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection at screening
- •Participants with current hepatitis A infection, or hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection (confirmed by HCV antibody) at screening
- •Participants with active acute respiratory infection at admission (Study Day -1 or -2)
研究组 & 干预措施
Cohort 1
Participants will receive placebo or JNJ-53718678 500 milligram (mg) or 200 mg once daily for 7 days.
干预措施: Placebo (Drug)
Cohort 1
Participants will receive placebo or JNJ-53718678 500 milligram (mg) or 200 mg once daily for 7 days.
干预措施: JNJ-53718678 (Drug)
Cohort 2
Participants will receive placebo or JNJ-53718678; dosing regimen in Cohort 2 will be decided based on Cohort 1 results.
干预措施: Placebo (Drug)
Cohort 2
Participants will receive placebo or JNJ-53718678; dosing regimen in Cohort 2 will be decided based on Cohort 1 results.
干预措施: JNJ-53718678 (Drug)
Cohort 3
Participants will receive placebo or JNJ-53718678, 75 mg once daily for 7 days.
干预措施: Placebo (Drug)
Cohort 3
Participants will receive placebo or JNJ-53718678, 75 mg once daily for 7 days.
干预措施: JNJ-53718678 (Drug)
结局指标
主要结局
Area Under the Viral Load-time Curve (VL AUC)
时间窗: up to Follow-up (Day 28)
VL AUC for RSV-A Memphis 37b will be determined by quantitative reverse transcriptase -polymerase chain reaction (qRT-PCR) assay of nasal wash. The VL AUC will be calculated based on the viral load values measured 2 times per day, starting with the last value prior to first dosing, and ending with the last available value before discharge.
次要结局
- Tissue Count(Baseline up to Day 13)
- Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 24 Hours after First Dose(24 hours after first dose)
- Area Under the Viral Load-time Curve (VL AUC) Determined by Plaque Forming Unit (PFU) Assay(Baseline up to Follow-up (Day 28))
- Viral Load Over Time(Baseline up to Follow-up (Day 28))
- Time To Peak Viral Load(Baseline up to Follow-up (Day 28))
- Peak Viral Load(Baseline up to Follow-up (Day 28))
- Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 48 Hours after First Dose(48 hours after first dose)
- Sequence Analysis of the Rsv-A Memphis 37b Genome(Baseline and post-Baseline)
- Total Clinical Symptom Score(Admission (Day -1 or -2) up to Day 13)
- FEV1/FVC Ratio(Baseline up to Follow-up (Day 28))
- Time to Non-detectability of Virus(Baseline up to Follow-up (Day 28))
- Time to Peak Symptom Score After Viral Inoculation(Admission (Day -1 or -2) up to Day 13)
- Mucus Weight(Baseline up to Day 13)
- Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry(Baseline up to Follow-up (Day 28))
- Forced Vital Capacity (FVC) Measured by Spirometry(Baseline up to Follow-up (Day 28))