The purpose of this study is to determine in hospitalized infants and children who are infected with respiratory syncytial virus (RSV) the dose-response relationship of multiple regimens of lumicitabine on antiviral activity based on nasal RSV shedding using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR).
RSV is a leading cause of lower respiratory tract disease in infants. Most infants and children who get RSV recover fully after 1-2 weeks, but RSV infection can sometimes worsen and may lead to hospitalization and admission into an intensive care unit. The main purpose of this study is to learn how well the study drug (lumicitabine, also known as JNJ-64041575 or ALS-008176) works, how the human body handles the study drug, which dose of the study drug is effective for treatment of RSV infection in infants/children and how safe it is compared to a placebo (placebo looks just like lumicitabine \[given in same way\] but has no effect against RSV). Approximately up to 180 participants aged between 28 days to 36 months and hospitalized with RSV infection will take part in this world-wide study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
7
Participants will receive oral administration of lumicitabine.
Participants will receive oral administration of matching placebo.
MemorialCare Research Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
The Children's Mercy Hospital
Kansas City, Missouri, United States
SUNY Upstate Medical University
Syracuse, New York, United States
Jacobi Medical Center
The Bronx, New York, United States
West Virginia University
Morgantown, West Virginia, United States
Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
AUC of RSV viral load was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay of the mid-turbinate nasal swab.
Time frame: Day 1 to 7: Predose, 0.25 and 2 hours postdose
Number of Participants With Emergent Adverse Event
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. All AEs reported during treatment or follow-up were considered emergent and were included in the analysis.
Time frame: Up to 28 days
Number of Participants With Clinically Significant Physical Examinations Abnormalities
The number of participants with clinically significant physical examination (respiratory system, nose, ear, throat, facial and neck lymph nodes, and skin examination) abnormalities that emerged after treatment initiation was reported.
Time frame: Up to 28 days
Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities
The number of participants with emergent clinically relevant vital signs (temperature, pulse rate, respiratory rate, diastolic blood pressure, systolic blood pressure, oxygen saturation) abnormalities that emerged after treatment initiation reported. An abnormality was considered emergent in a particular phase if it is worse than baseline. If baseline is missing, the abnormality is always considered as emergent. A shift from 'abnormally low' at baseline to 'abnormally high' post baseline (or vice versa) was also emergent.
Time frame: Up to 28 days
Number of Participants With Electrocardiogram (ECG) Abnormalities
The number of participants with ECG (QT, and QTc intervals) abnormalities reported.
Time frame: Up to 28 days
Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades)
Number of participants with Laboratory (hematology, serum chemistry, and urinalysis) abnormalities reported based on DMID toxicity grading scale. DMID toxicity grades ranges from 1 to 4. Grade 0 is normal and not meeting the criteria of Grade 1-4. Hb: Grade 1: for 22-35 days old- 9.5-10.5 gram per deciliter (g/dL); for 36-60 days old- 8.5-9.4 g/dL; for 61-90 days old- 9.0-9.9 g/dL; Hb: Grade 2: for 22-35 days old- 8.0-9.4 g/dL, for 36-60 days old- 7.0-8.4 g/dL; for 61-90 days old- 7.0-8.9 g/dL. ALT: Grade 1- 1.1 - \<2.0\*Upper limit of normal (ULN); Creatinine: Grade 2- 1.8-2.4 milligram per deciliter (mg/dL); Hyperkalemia: Grade 1- 3.0-3-5 milliequivalents per Liter (mEq/L); ANC: Grade 1: for 7-60 days old- 1200-1800/ millimeter cube(mm\^3); for 61-90 days old- 750-1200/mm\^3; ANC: Grade 3: for 7-60 days old- 500-899/mm\^3, for 61-90 days old- 250-399/mm\^3; ANC: Grade 4- for 7-60 days old \<500/mm\^3, for 61-90 days old- \<250/mm\^3; Platelets: Grade 3: 25000 - 49999/mm\^3.
Time frame: Up to 28 days
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine)
Cmax is the maximum observed plasma concentration of JNJ-63549109 (Metabolite of Lumicitabine).
Time frame: Day 1 and Day 5
Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine)
AUC is the area under the plasma concentration-time curve of JNJ-63549109 (Metabolite of Lumicitabine).
Time frame: Day 1 and Day 5
Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine)
C(trough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen of JNJ-63549109 (Metabolite of Lumicitabine).
Time frame: Day 1 and Day 5
Predicted Concentration of JNJ-63549109 (Metabolite of Lumicitabine) at 12 Hours Postdose (C12h)
C12h is the predicted concentration of JNJ-63549109 at 12 hours Postdose. C12h is a model-based prediction. It was determined using a population pharmacokinetic (PK) model and based on the individual model predicted concentration-time profiles.
Time frame: 12 hours postdose
Length of Hospital Stay
Length of hospital stay is defined as the time from hospitalization to actual hospital discharge.
Time frame: Up to 28 days
Number of Participants Admitted to the Intensive Care Unit (ICU)
Number of participants who were admitted to the ICU was reported.
Time frame: Up to 28 days
Duration of ICU Stay
In the event that a participant required ICU, the duration for how long the participant remained in the ICU was reported.
Time frame: Up to 28 days
Number of Participants Who Required Supplemental Oxygen
The number of participants who required supplemental oxygen above pre-RSV infection status was reported.
Time frame: Up to 28 days
Number of Participants Who Required Non-invasive Mechanical Ventilation Support
The number of participants who required non-invasive mechanical ventilation support (that is, continuous positive airway pressure) above pre-RSV infection status was reported.
Time frame: Up to 28 days
Number of Participants Who Required Invasive Mechanical Ventilation Support
The number of participants who required invasive mechanical ventilation support (for example, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) above pre-RSV infection status was reported.
Time frame: Up to 28 days
Duration of Supplemental Oxygen
Duration of supplemental oxygen above pre-RSV infection status was assessed.
Time frame: Up to 28 days
Duration of Non-invasive Mechanical Ventilation Support
Duration of non-invasive mechanical ventilation support (that is, continuous positive airway pressure) to deliver oxygen above pre-RSV infection status was measured.
Time frame: Up to 28 days
Duration of Invasive Mechanical Ventilation Support
Duration of invasive mechanical ventilation support (for example, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) to deliver oxygen above pre-RSV infection status was measured.
Time frame: Up to 28 days
Time to no Longer Requiring Supplemental Oxygen
Time to no longer requiring supplemental oxygen above pre-RSV infection status was reported.
Time frame: Up to 28 days
Time to Clinical Stability
Time to clinical stability was defined as the time at which the following criteria are all met: normalization of blood oxygen level (return to baseline, by pulse oximetry) without the requirement of supplemental oxygen beyond baseline level, normalization of oral feeding, normalization of respiratory rate, and normalization of heart rate.
Time frame: Up to 28 days
Time From Initiation of Study Treatment Until Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to (>=)93 Percent (%) on Room Air Among Participants Who Were Not on Supplemental Oxygen Prior to Onset of Respiratory Symptoms
Time from initiation of study treatment until SpO2 \>=93% on room air among participants who were not on supplemental oxygen prior to the onset of respiratory symptoms was reported.
Time frame: Up to 28 days
Time for Respiratory Rate to Return to Pre-RSV Infection Status
Time for the respiratory rate to return to pre-RSV infection status was measured.
Time frame: Up to 28 days
Time for SpO2 to Return to Pre-RSV Infection Status
Time for SpO2 to return to pre-RSV infection status was measured.
Time frame: Up to 28 days
Time for Body Temperature to Return To Pre-RSV Infection Status
Time for body temperature to return to pre-RSV infection status was measured.
Time frame: Up to 28 days
Number of Participants With Acute Otitis Media
Number of participants with acute otitis media was reported.
Time frame: Up to 28 days
Duration of Signs and Symptoms of RSV Infection
Duration of signs and symptoms of RSV infection was assessed.
Time frame: Up to 28 days
Severity of Signs and Symptoms of RSV Infection Assessed by the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS)
The severity of signs and symptoms of RSV infection were assessed by the PRESORS. PRESORS Score consisted of 5-items, each score ranges from 0 to 3 and the total score was analyzed by summing up the individual score ranging from 0 (minimum; best) to 15 (maximum; worse).
Time frame: Up to 28 days
RSV Viral Load Over Time
RSV viral load over time was measured by qRT-PCR in the mid-turbinate nasal swab specimens.
Time frame: On Day 2, 3, 4, 5, 6, 7, 10, 14 and 28
Peak Viral Load
Peak viral load was measured by qRT-PCR in the mid-turbinate nasal swab specimens.
Time frame: Up to 28 days
Time To Peak Viral Load
Time to peak viral load was reported.
Time frame: Up to 28 days
Percentage of Participants With Decline of Viral Load
Percentage of participants with decline in viral load during treatment as measured by qRT-PCR was reported.
Time frame: Up to 28 days
Time to RSV Ribonucleic Acid (RNA) Being Undetectable
Time to RSV RNA being undetectable (the time from initiation of study treatment until the time at which it is observed that the virus is undetectable in an assessment and after which time no virus positive assessment follows) was assessed as measured by qRT-PCR.
Time frame: Up to 28 days
Percentage of Participants With Undetectable RSV Viral Load
Percentage of participants with the undetectable viral load was reported.
Time frame: Up to 28 days
AUC of RSV RNA Viral Load From Baseline up to Day 10
AUC of RSV RNA viral load was measured in mid-turbinate nasal swabs and in the endotracheal sample.
Time frame: Baseline up to Day 10
AUC of RSV RNA Viral Load From Baseline up to Day 14
AUC of RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples.
Time frame: Baseline up to Day 14
AUC of RSV Viral Load From Baseline Until 1 Day After the Last Dose of Study Drug
AUC of RSV viral load was measured in midturbinate nasal swabs and in endotracheal samples.
Time frame: Baseline Until 1 Day after the last dose of study drug (up to 10 days)
Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences
Number of participants with emergent postbaseline changes in the RSV polymerase L-gene and other regions of the RSV genome compared with baseline sequences were reported.
Time frame: Baseline up to 28 days
Acceptability and Palatability of Lumicitabine Formulation as Assessed by Clinician Electronic Clinical Outcome Assessment (eCOA)
Acceptability and Palatability of lumicitabine formulation was assessed by clinician eCOA questionnaire ranging from score 0 (minimum; best) to 8 (maximum; worse).
Time frame: Up to Day 6
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