A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) Regimens in Hospitalized Adult Subjects Infected With Human Metapneumovirus
Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Oral Lumicitabine Regimens in Hospitalized Adult Participants Infected With Human Metapneumovirus
Janssen Pharmaceutical K.K., Japan
Tel: 0120-183-275, Fax: 0120-275-831 Office Hour: 9:00 - 17:40 (Closed on Saturdays, Sundays, Public Holidays and Company Holidays)
- Participants hospitalized (or in Emergency room prior to hospitalization) at the time of randomization and unlikely to be discharged for the first 24 hours after randomization
- Participants diagnosed with human metapneumovirus (hMPV) infection using a rapid polymerase chain reaction (PCR)-based molecular diagnostic assay, with or without coinfection with another respiratory pathogen (respiratory virus or bacteria)
- Participants with an acute respiratory illness with signs and symptoms consistent with a viral infection (for example, fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) with onset less than or equal to (<=)5 days from the anticipated time of randomization
- With the exception of the symptoms related to hMPV infection, participants must be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population, and/or the hMPV infection. This determination must be recorded in the participant's source documents and initialed by the investigator
- A woman must have a negative urine pregnancy test (beta-human chorionic gonadotropin [b-hCG]) at screening
- Participants who are not expected to survive for more than 48 hours
- Participants who have had major thoracic or abdominal surgery in the 6 weeks prior to randomization
- Participants who are considered by the investigator to be immunocompromised within the past 12 months, whether due to underlying medical condition (for example, malignancy or genetic disorder) or medical therapy (for example, medications other than corticosteroids for the treatment of chronic obstructive pulmonary disease (COPD) or asthma exacerbations, chemotherapy, radiation, stem cell or solid organ transplant)
- Participants undergoing peritoneal dialysis, hemodialysis, or hemofiltration or with an estimated glomerular filtration rate (GFR, determined by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) of (<) 60 milliliters per minute (mL/min) per 1.73 meter square (m^2)
- Participants with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis
20age old over
No limit
Both
Metapneumovirus
investigational material(s)
Generic name etc : Lumicitabine
INN of investigational material :
Therapeutic category code : 625 Anti-virus agents
Dosage and Administration for Investigational material : Regimen A (Low-Dose Lumicitabine) Participants will receive a single 750 milligram (mg) loading dose (LD) (Dose 1) of lumicitabine Regimen B (High-Dose Lumicitabine) Participants will receive a single 1000 mg LD (Dose 1) of lumicitabine followed by nine 500 mg tablets as MDs (Doses 2 to 10) of lumicitabine
control material(s)
Generic name etc : Placebo
INN of investigational material :
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Regimen C (Placebo) Participants will receive a placebo LD (Dose 1) followed by nine MDs (Doses 2 to 10) of matching placebo, administered twice daily during Day 1 to Day 5/6 (depending on the timing of the LD).
Area Under the Concentration-Time Curve (AUC) of Human Metapneumovirus (hMPV) Viral Load Baseline up to Day 7
The AUC of hMPV ribonucleic acid (RNA) logarithm base 10 (log10) viral load (measured by quantitative real time reverse transcriptase polymerase chain reaction [qRT-PCR] in the mid-turbinate nasal swab specimens) is estimated by analyzing mean log10 viral load values over time using a restricted maximum likelihood based repeated measures approach.
Baseline up to Day 7
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Up to 28 days
Number of Participants with an Abnormal Physical Examination Findings (Height, Body Weight, Respiratory System, Nose, Ear, Throat, Facial and Neck Lymph Nodes, and Skin Examination) as a Measure of Safety and Tolerability
Up to 28 days
Number of Participants with an Abnormal Vital Signs/Peripheral Capillary Oxygen Saturation (SpO2) Reading as a Measure of Safety and Tolerability
Up to 28 days
Number of Participants with an Abnormal Electrocardiogram (ECG) Reading as a Measure of Safety and Tolerability
Up to 28 days
Number of Participants with Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability
Up to 28 days
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109
Dose 1: 0.5 to 1 hour postdose, and 2 to 3 hours postdose; Dose 2: predose, and 3 to 6 hours postdose; Dose 3 and 10: predose
Concentration at 12 Hours Postdose (C12h) of JNJ-63549109
Days 1, 2, and 5/6: 12 hours postdose
Area Under the Plasma Concentration-Time Curve (AUC) of JNJ-63549109
Dose 1: 0.5 to 1 hour postdose, and 2 to 3 hours postdose; Dose 2: predose, and 3 to 6 hours postdose; Dose 3 and 10: predose
Ordinal Scale
Day of last dose (Day 5 or Day 6)
Length of Hospital Stay from Admission to Discharge
From admission to discharge (Up to 28 days)
Length of Hospital Stay from Admission to Readiness for Discharge
From admission to readiness for discharge discharge (Up to 28 days)
Length of Hospital Stay from Study Treatment Initiation to Discharge
From study treatment initiation to discharge (Up to 28 days)
Length of Hospital Stay from Study Treatment Initiation to Readiness for Discharge
From study treatment initiation to readiness for discharge (Up to 28 days)
Percentage of Participants Requiring Admission to the Intensive Care Unit (ICU)
Up to 28 days
Duration of ICU Stay
Up to 28 days
Percentage of Participants Requiring Oxygen Supplementation/Noninvasive Mechanical Ventilation Support
Up to 28 days
Duration of Oxygen Supplementation/Noninvasive Mechanical Ventilation Support
Up to 28 days
Percentage of Participants Requiring Invasive Mechanical Ventilation Support
Up to 28 days
Duration of Invasive Mechanical Ventilation Support
Up to 28 days
Time to no Longer Requiring Supplemental Oxygen
Up to 28 days
Time to Clinical Stability
Up to 28 days
Number of Hours from Initiation of Study Treatment Until SpO2 is Greater Than or equal to (>=) 93 Percent (%) on Room air
Up to 28 days
Time for Respiratory Rate to Return to Pre-hMPV Infection Status
Up to 28 days
Time for Peripheral Capillary Oxygen Saturation (SpO2) Return to Pre-hMPV Infection Status
Up to 28 days
Time for Body Temperature to Return to Pre-hMPV Infection Status
Up to 28 days
Percentage of Enrolled Participants Who Require Hydration and/or Feeding by Intravenous (IV) Catheter or Nasogastric Tube
Up to 28 days
Number of Participants With Bacterial uperinfections Reported as AEs
Up to 28 days
Number of Participants With Treatment- Emergent Complications
Up to 28 days
Change From Baseline in the National Early Warning Score (NEWS) Over Time
Baseline up to 28 days
Number of Participants With All-Cause Mortality Up to 28 days
Up to 28 days
Time to Return to Pre-hMPV Infection Functional Status (Katz Activities of Daily Living [ADL] score)
Up to 28 days
hMPV Viral Load Over Time
Up to 28 days
Peak hMPV Viral Load
Up to 28 days
Time to Peak hMPV Viral Load
Up to 28 days
Rate of Decline of hMPV Viral Load
Up to 28 days
Time to hMPV Ribonucleic Acid (RNA) Being Undetectable
Up to 28 days
Percentage of Participants With Undetectable hMPV Viral Load at Each Timepoint
From Day 1 to Day 7 and on Day 10, Day 14, and Day 28
AUC of hMPV Viral Load From Baseline up to Day 10
Baseline up to Day 10
AUC of hMPV Viral Load from Baseline up to Day 14
Baseline up to Day 14
AUC of hMPV Viral Load in Participants Assigned to a Longer Dosing Duration From Baseline Until 1 day After the Last Dose of Study Drug
Baseline Until 1 day After the Last Dose of Study Drug (approximately up to 12 days)
Number of Participants With Postbaseline Changes in the hMPV Polymerase Lgene and Other Regions of the hMPV Genome Compared With Baseline Sequences
Up to 28 days
