Respiratory Syncytial Viruses
Conditions
Brief summary
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).
Detailed description
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.
Interventions
DRUGLumicitabine
Participants will receive oral administration of lumicitabine.
DRUGPlacebo
Participants will receive oral administration of matching placebo.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
28 Days to 36 Months
Healthy volunteers
No
Inclusion criteria
* Participants hospitalized (or in emergency room \[ER\]) at the time of randomization and unlikely to be discharged for the first 24 hours after randomization * Participants diagnosed with respiratory syncytial virus (RSV) infection using a polymerase chain reaction (PCR)-based molecular diagnostic assay, with or without co-infection with another respiratory pathogen (respiratory virus or bacteria) * Participants who have 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. Onset of symptoms is defined as the first time (within 1 hour) the parent(s)/caregiver(s) becomes aware of respiratory or systemic symptoms of RSV infection * With the exception of the symptoms related to the RSV infection or defined comorbid condition for severe RSV disease (prematurity at birth \[participant's gestational age was less than {\<}37 weeks; for infants \<1 year old at randomization\], bronchopulmonary dysplasia, congenital heart disease, other congenital diseases, Down syndrome, neuromuscular impairment, or cystic fibrosis), participant must be medically stable on the basis of physical examination, medical history, vital signs/peripheral capillary oxygen saturation (SpO2), and electrocardiogram (ECG) performed at screening. If there are abnormalities, they must be consistent with the underlying condition in the study population and/or the RSV infection. This determination must be recorded in the participant's source documents and initialed by the investigator. Participants with comorbidities will be allowed to be enrolled once the Independent Data Monitoring Committee (IDMC) has reviewed the pharmacokinetic (PK) and safety data of the highest dose that will be used in this study and once the IDMC has recommended opening recruitment to this group. Sites will be notified when the restriction is lifted * The participant's estimated glomerular filtration rate (eGFR) is not below the lower limit of normal for the participant's age
Exclusion criteria
* 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 have a known or suspected immunodeficiency (except immunoglobulin A \[IgA\] deficiency), such as a known human immunodeficiency virus infection * Participants being treated with extracorporeal membrane oxygenation * Participant receiving chronic oxygen therapy at home prior to admission * Participants who have a poorly functioning gastrointestinal tract (that is, unable to absorb drugs or nutrition via enteral route)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load | Day 1 to 7: Predose, 0.25 and 2 hours postdose | AUC of RSV viral load was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay of the mid-turbinate nasal swab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Emergent Adverse Event | Up to 28 days | 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. |
| Number of Participants With Clinically Significant Physical Examinations Abnormalities | Up to 28 days | 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. |
| Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Up to 28 days | 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. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities | Up to 28 days | The number of participants with ECG (QT, and QTc intervals) abnormalities reported. |
| Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Up to 28 days | 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. |
| Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 and Day 5 | Cmax is the maximum observed plasma concentration of JNJ-63549109 (Metabolite of Lumicitabine). |
| Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 and Day 5 | AUC is the area under the plasma concentration-time curve of JNJ-63549109 (Metabolite of Lumicitabine). |
| Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 and Day 5 | 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). |
| Predicted Concentration of JNJ-63549109 (Metabolite of Lumicitabine) at 12 Hours Postdose (C12h) | 12 hours postdose | 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. |
| Length of Hospital Stay | Up to 28 days | Length of hospital stay is defined as the time from hospitalization to actual hospital discharge. |
| Number of Participants Admitted to the Intensive Care Unit (ICU) | Up to 28 days | Number of participants who were admitted to the ICU was reported. |
| Duration of ICU Stay | Up to 28 days | In the event that a participant required ICU, the duration for how long the participant remained in the ICU was reported. |
| Number of Participants Who Required Supplemental Oxygen | Up to 28 days | The number of participants who required supplemental oxygen above pre-RSV infection status was reported. |
| Number of Participants Who Required Non-invasive Mechanical Ventilation Support | Up to 28 days | The number of participants who required non-invasive mechanical ventilation support (that is, continuous positive airway pressure) above pre-RSV infection status was reported. |
| Number of Participants Who Required Invasive Mechanical Ventilation Support | Up to 28 days | 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. |
| Duration of Supplemental Oxygen | Up to 28 days | Duration of supplemental oxygen above pre-RSV infection status was assessed. |
| Duration of Non-invasive Mechanical Ventilation Support | Up to 28 days | Duration of non-invasive mechanical ventilation support (that is, continuous positive airway pressure) to deliver oxygen above pre-RSV infection status was measured. |
| Duration of Invasive Mechanical Ventilation Support | Up to 28 days | 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 to no Longer Requiring Supplemental Oxygen | Up to 28 days | Time to no longer requiring supplemental oxygen above pre-RSV infection status was reported. |
| Time to Clinical Stability | Up to 28 days | 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 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 | Up to 28 days | 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 for Respiratory Rate to Return to Pre-RSV Infection Status | Up to 28 days | Time for the respiratory rate to return to pre-RSV infection status was measured. |
| Time for SpO2 to Return to Pre-RSV Infection Status | Up to 28 days | Time for SpO2 to return to pre-RSV infection status was measured. |
| Time for Body Temperature to Return To Pre-RSV Infection Status | Up to 28 days | Time for body temperature to return to pre-RSV infection status was measured. |
| Number of Participants With Acute Otitis Media | Up to 28 days | Number of participants with acute otitis media was reported. |
| Duration of Signs and Symptoms of RSV Infection | Up to 28 days | Duration of signs and symptoms of RSV infection was assessed. |
| Severity of Signs and Symptoms of RSV Infection Assessed by the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS) | Up to 28 days | 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). |
| RSV Viral Load Over Time | On Day 2, 3, 4, 5, 6, 7, 10, 14 and 28 | RSV viral load over time was measured by qRT-PCR in the mid-turbinate nasal swab specimens. |
| Peak Viral Load | Up to 28 days | Peak viral load was measured by qRT-PCR in the mid-turbinate nasal swab specimens. |
| Time To Peak Viral Load | Up to 28 days | Time to peak viral load was reported. |
| Percentage of Participants With Decline of Viral Load | Up to 28 days | Percentage of participants with decline in viral load during treatment as measured by qRT-PCR was reported. |
| Time to RSV Ribonucleic Acid (RNA) Being Undetectable | Up to 28 days | 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. |
| Percentage of Participants With Undetectable RSV Viral Load | Up to 28 days | Percentage of participants with the undetectable viral load was reported. |
| AUC of RSV RNA Viral Load From Baseline up to Day 10 | Baseline up to Day 10 | AUC of RSV RNA viral load was measured in mid-turbinate nasal swabs and in the endotracheal sample. |
| AUC of RSV RNA Viral Load From Baseline up to Day 14 | Baseline up to Day 14 | AUC of RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples. |
| AUC of RSV Viral Load From Baseline Until 1 Day After the Last Dose of Study Drug | Baseline Until 1 Day after the last dose of study drug (up to 10 days) | AUC of RSV viral load was measured in midturbinate nasal swabs and in endotracheal samples. |
| Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences | Baseline up to 28 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 were reported. |
| Acceptability and Palatability of Lumicitabine Formulation as Assessed by Clinician Electronic Clinical Outcome Assessment (eCOA) | Up to Day 6 | Acceptability and Palatability of lumicitabine formulation was assessed by clinician eCOA questionnaire ranging from score 0 (minimum; best) to 8 (maximum; worse). |
Countries
Belgium, Canada, Hungary, Japan, Poland, United States
Participant flow
Recruitment details
On 17 October 2018, the study was stopped prematurely by the sponsor as a precautionary measure, to allow further evaluation and assessment of the new nonclinical pharmacokinetics (PK) and safety findings and determine their relevance to human studies.
Pre-assignment details
Total 7 participants were randomized to receive lumicitabine or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single dose of lumicitabine-40 milligrams/kilogram (mg/kg) matched placebo as a loading dose (LD) (Dose 1) followed by 9 maintenance dose (MD) of lumicitabine-20 mg/kg matched placebo twice a day or a single dose of lumicitabine-60 mg/kg matched placebo LD (Dose 1) followed by nine lumicitabine-40 mg/kg matched placebo MD (Dose 2 to 10). | 3 |
| Lumicitabine 40/20 mg/kg LD/MD Participants received a single dose of lumicitabine-40 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 20 mg/kg twice a day. | 1 |
| Lumicitabine 60/40 mg/kg LD/MD Participants received a single dose of lumicitabine-60 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 40 mg/kg twice a day. | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | Placebo | Lumicitabine 40/20 mg/kg LD/MD | Lumicitabine 60/40 mg/kg LD/MD | Total |
|---|---|---|---|---|
| Age, Continuous | 16 months STANDARD_DEVIATION 13.08 | 17 months | 6.3 months STANDARD_DEVIATION 2.52 | 12 months STANDARD_DEVIATION 9.35 |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment JAPAN | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 1 / 1 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 1 | 1 / 3 |
Outcome results
Primary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: ITT set was defined as all randomized participants who receive at least 1 dose of study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 | 12700 nanogram hour per milliliters (ng*h/ml) | — |
| Placebo | Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 5 | 11840 nanogram hour per milliliters (ng*h/ml) | — |
| Lumicitabine 40/20 mg/kg LD/MD | Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 | 17800 nanogram hour per milliliters (ng*h/ml) | Standard Deviation 713.9 |
| Lumicitabine 40/20 mg/kg LD/MD | Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 5 | 20500 nanogram hour per milliliters (ng*h/ml) | Standard Deviation 655.7 |
Secondary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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)
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: No participant was admitted to ICU hence results could not be determined for this outcome measure.
Secondary
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
Population: No participant received invasive mechanical ventilation support hence results could not be drawn for this outcome measure.
Secondary
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
Population: No participant received non-invasive mechanical ventilation support hence results could not be drawn for this outcome measure.
Secondary
Duration of Signs and Symptoms of RSV Infection
Duration of signs and symptoms of RSV infection was assessed.
Time frame: Up to 28 days
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
Duration of Supplemental Oxygen
Duration of supplemental oxygen above pre-RSV infection status was assessed.
Time frame: Up to 28 days
Population: Population included randomized or treated set who received supplemental oxygen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Duration of Supplemental Oxygen | 59.4 Hours |
| Lumicitabine 40/20 mg/kg LD/MD | Duration of Supplemental Oxygen | 0.5 Hours |
Secondary
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
Population: Population included randomized or treated set. As the study was early terminated with fewer participants than planned, results for this endpoint could not be summarized. Hence, individual data for each participant was reported. Here, n (number analyzed) signifies specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Length of Hospital Stay | Participant 2 | 167.8 Hours |
| Placebo | Length of Hospital Stay | Participant 1 | 143.5 Hours |
| Placebo | Length of Hospital Stay | Participant 3 | 179.4 Hours |
| Lumicitabine 40/20 mg/kg LD/MD | Length of Hospital Stay | Participant 4 | 167.8 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Length of Hospital Stay | Participant 6 | 239.5 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Length of Hospital Stay | Participant 5 | 120 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Length of Hospital Stay | Participant 7 | 149.3 Hours |
Secondary
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
Population: Intent to Treat (ITT) set was defined as all randomized participants who receive at least 1 dose of study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 | 6184 nanogram/milliliter (ng/ml) | — |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 5 | 3261 nanogram/milliliter (ng/ml) | — |
| Lumicitabine 40/20 mg/kg LD/MD | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 | 7003 nanogram/milliliter (ng/ml) | Standard Deviation 3806 |
| Lumicitabine 40/20 mg/kg LD/MD | Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 5 | 5112 nanogram/milliliter (ng/ml) | Standard Deviation 1665 |
Secondary
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
Population: Randomized or Treated set was defined as all participants who were in the Randomized Analysis Set (all randomized participants with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Admitted to the Intensive Care Unit (ICU) | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants Admitted to the Intensive Care Unit (ICU) | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants Admitted to the Intensive Care Unit (ICU) | 0 Participants |
Secondary
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
Population: Randomized or Treated set was defined as all participants who were in the Randomized Analysis Set (all randomized participants with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Required Invasive Mechanical Ventilation Support | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants Who Required Invasive Mechanical Ventilation Support | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants Who Required Invasive Mechanical Ventilation Support | 0 Participants |
Secondary
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
Population: Randomized or Treated set was defined as all participants who were in the Randomized Analysis Set (all randomized participants with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Required Non-invasive Mechanical Ventilation Support | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants Who Required Non-invasive Mechanical Ventilation Support | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants Who Required Non-invasive Mechanical Ventilation Support | 0 Participants |
Secondary
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
Population: Randomized or Treated set was defined as all participants who were in the Randomized Analysis Set (all randomized participants with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Required Supplemental Oxygen | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants Who Required Supplemental Oxygen | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants Who Required Supplemental Oxygen | 0 Participants |
Secondary
Number of Participants With Acute Otitis Media
Number of participants with acute otitis media was reported.
Time frame: Up to 28 days
Population: Randomized or Treated set was defined as all participants who were in the Randomized Analysis Set (all randomized participants with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Acute Otitis Media | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Acute Otitis Media | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Acute Otitis Media | 0 Participants |
Secondary
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
Population: Randomized or Treated set was defined as all participants who were in Randomized Analysis Set (all randomized participants with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or all participants treated (AST) set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Physical Examinations Abnormalities | 2 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Clinically Significant Physical Examinations Abnormalities | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Clinically Significant Physical Examinations Abnormalities | 1 Participants |
Secondary
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
Population: Safety analysis set was defined as all participants who received at least 1 dose of study drug, analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Bazett's Correction Formula | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT Duration | 1 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Fridericia's Correction Formula | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Bazett's Correction Formula | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Fridericia's Correction Formula | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT Duration | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Fridericia's Correction Formula | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT Duration | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Bazett's Correction Formula | 0 Participants |
Secondary
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
Population: Safety analysis set was defined as all participants who received at least 1 dose of study drug, analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Emergent Adverse Event | 3 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Adverse Event | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Adverse Event | 3 Participants |
Secondary
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
Population: Safety analysis set was defined as all participants who received at least 1 dose of study drug, analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Diastolic Blood Pressure (Abnormally high) | 1 Participants |
| Placebo | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Respiratory Rate (Abnormally high) | 0 Participants |
| Placebo | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Pulse Rate (Abnormally high) | 1 Participants |
| Placebo | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Oxygen Saturation (Abnormally low) | 1 Participants |
| Placebo | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Temperature (High) | 1 Participants |
| Placebo | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Systolic Blood Pressure (Abnormally high) | 2 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Systolic Blood Pressure (Abnormally high) | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Pulse Rate (Abnormally high) | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Diastolic Blood Pressure (Abnormally high) | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Respiratory Rate (Abnormally high) | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Temperature (High) | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Oxygen Saturation (Abnormally low) | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Pulse Rate (Abnormally high) | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Oxygen Saturation (Abnormally low) | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Temperature (High) | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Diastolic Blood Pressure (Abnormally high) | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Systolic Blood Pressure (Abnormally high) | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities | Respiratory Rate (Abnormally high) | 1 Participants |
Secondary
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
Population: Randomized or Treated set was defined as all participants who were in Randomized Analysis Set (all randomized participants with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or all participants treated (AST) set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences | 0 Participants |
Secondary
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
Population: Safety analysis set was defined as all participants who received at least 1 dose of study drug, analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Platelets: Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hemoglobin (Hb): Grade 0 | 2 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 4 | 0 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypernatremia: Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyponatremia: Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperglycemia: Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ALT: Grade 1 | 0 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypokalemia: Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hb: Grade 1 | 1 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperkalemia: Grade 1 | 2 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperkalemia: Grade 0 | 1 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Creatinine: Grade 2 | 0 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Alanine transaminase (ALT): Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypoglycemia: Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 3 | 0 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Aspartate Aminotransferase (AST): Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 1 | 1 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Absolute neutrophil count (ANC): Grade 0 | 2 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Bilirubin: Grade 0 | 3 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Platelets: Grade 3 | 0 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hb: Grade 2 | 0 Participants |
| Placebo | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Creatinine: Grade 0 | 3 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Aspartate Aminotransferase (AST): Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ALT: Grade 1 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hemoglobin (Hb): Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Absolute neutrophil count (ANC): Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Alanine transaminase (ALT): Grade 0 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Bilirubin: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Creatinine: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Creatinine: Grade 2 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypoglycemia: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperglycemia: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypokalemia: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperkalemia: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperkalemia: Grade 1 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyponatremia: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypernatremia: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hb: Grade 1 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hb: Grade 2 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 1 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 3 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 4 | 0 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Platelets: Grade 0 | 1 Participants |
| Lumicitabine 40/20 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Platelets: Grade 3 | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 4 | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hb: Grade 1 | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Bilirubin: Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperglycemia: Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hb: Grade 2 | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Aspartate Aminotransferase (AST): Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Absolute neutrophil count (ANC): Grade 0 | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Alanine transaminase (ALT): Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Platelets: Grade 3 | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 1 | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ALT: Grade 1 | 0 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Platelets: Grade 0 | 2 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperkalemia: Grade 0 | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypokalemia: Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | ANC: Grade 3 | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyperkalemia: Grade 1 | 2 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hyponatremia: Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Creatinine: Grade 2 | 1 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypoglycemia: Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hypernatremia: Grade 0 | 3 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Creatinine: Grade 0 | 2 Participants |
| Lumicitabine 60/40 mg/kg LD/MD | Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) | Hemoglobin (Hb): Grade 0 | 2 Participants |
Secondary
Peak Viral Load
Peak viral load was measured by qRT-PCR in the mid-turbinate nasal swab specimens.
Time frame: Up to 28 days
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: ITT-i set was defined as all randomly assigned participants who receive at least 1 dose of study drug and who have an RSV infection confirmed by a PCR-based assay at baseline or within 1 hour after the first study medication intake at the central laboratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Decline of Viral Load | 100 Percentage of participants |
| Lumicitabine 40/20 mg/kg LD/MD | Percentage of Participants With Decline of Viral Load | 100 Percentage of participants |
| Lumicitabine 60/40 mg/kg LD/MD | Percentage of Participants With Decline of Viral Load | 100 Percentage of participants |
Secondary
Percentage of Participants With Undetectable RSV Viral Load
Percentage of participants with the undetectable viral load was reported.
Time frame: Up to 28 days
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: Intention-To-Treat-infected (ITT-i) set was defined as all randomly assigned participants who receive at least 1 dose of study drug and who have an RSV infection confirmed by a polymerase chain reaction (PCR)-based assay at baseline or within 1 hour after the first study medication intake at the central laboratory.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | RSV Viral Load Over Time | Day 3 | 5.443 log10 per milliliters (log10/mL) | Standard Deviation 1.4645 |
| Placebo | RSV Viral Load Over Time | Day 5 | 3.808 log10 per milliliters (log10/mL) | Standard Deviation 1.0049 |
| Placebo | RSV Viral Load Over Time | Day 4 | 4.674 log10 per milliliters (log10/mL) | Standard Deviation 2.4209 |
| Placebo | RSV Viral Load Over Time | Day 14 | 1.900 log10 per milliliters (log10/mL) | Standard Deviation 0 |
| Placebo | RSV Viral Load Over Time | Day 28 | 1.900 log10 per milliliters (log10/mL) | Standard Deviation 0 |
| Placebo | RSV Viral Load Over Time | Day 2 | 5.817 log10 per milliliters (log10/mL) | Standard Deviation 2.2087 |
| Placebo | RSV Viral Load Over Time | Day 7 | 2.994 log10 per milliliters (log10/mL) | Standard Deviation 1.445 |
| Placebo | RSV Viral Load Over Time | Day 6 | 3.137 log10 per milliliters (log10/mL) | Standard Deviation 1.9306 |
| Placebo | RSV Viral Load Over Time | Day 10 | 2.821 log10 per milliliters (log10/mL) | Standard Deviation 1.595 |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 6 | 6.514 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 7 | 4.584 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 3 | 6.000 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 28 | 1.900 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 5 | 5.949 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 10 | 1.900 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 14 | 2.900 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 2 | 6.809 log10 per milliliters (log10/mL) | — |
| Lumicitabine 40/20 mg/kg LD/MD | RSV Viral Load Over Time | Day 4 | 2.900 log10 per milliliters (log10/mL) | — |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 28 | 1.900 log10 per milliliters (log10/mL) | Standard Deviation 0 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 3 | 5.351 log10 per milliliters (log10/mL) | Standard Deviation 0.5794 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 4 | 4.190 log10 per milliliters (log10/mL) | Standard Deviation 1.419 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 5 | 4.521 log10 per milliliters (log10/mL) | Standard Deviation 1.7506 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 10 | 3.573 log10 per milliliters (log10/mL) | Standard Deviation 0.761 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 6 | 4.110 log10 per milliliters (log10/mL) | Standard Deviation 1.698 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 7 | 2.754 log10 per milliliters (log10/mL) | Standard Deviation 1.2688 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 14 | 1.983 log10 per milliliters (log10/mL) | Standard Deviation 0.1443 |
| Lumicitabine 60/40 mg/kg LD/MD | RSV Viral Load Over Time | Day 2 | 6.660 log10 per milliliters (log10/mL) | Standard Deviation 0.9732 |
Secondary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: Population included randomized or treated set. As study was terminated early with fewer participants than planned, data was not summarized. Hence, individual data for each participant was reported. Here, n (number analyzed) signifies specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time for Body Temperature to Return To Pre-RSV Infection Status | Participant 1 | 0 Hours |
| Placebo | Time for Body Temperature to Return To Pre-RSV Infection Status | Participant 2 | 643.5 Hours |
| Placebo | Time for Body Temperature to Return To Pre-RSV Infection Status | Participant 3 | 37.4 Hours |
| Lumicitabine 40/20 mg/kg LD/MD | Time for Body Temperature to Return To Pre-RSV Infection Status | Participant 4 | 16.7 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for Body Temperature to Return To Pre-RSV Infection Status | Participant 5 | 0 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for Body Temperature to Return To Pre-RSV Infection Status | Participant 6 | 0 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for Body Temperature to Return To Pre-RSV Infection Status | Participant 7 | 641.6 Hours |
Secondary
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
Population: Population included randomized or treated set. As study was terminated early with fewer participants than planned, results for this endpoint could not be summarized. Hence, individual data for each participant was reported. Here, n (number analyzed) signifies specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time for Respiratory Rate to Return to Pre-RSV Infection Status | Participant 1 | 0 Hours |
| Placebo | Time for Respiratory Rate to Return to Pre-RSV Infection Status | Participant 2 | 39.5 Hours |
| Placebo | Time for Respiratory Rate to Return to Pre-RSV Infection Status | Participant 3 | 46.4 Hours |
| Lumicitabine 40/20 mg/kg LD/MD | Time for Respiratory Rate to Return to Pre-RSV Infection Status | Participant 4 | 0 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for Respiratory Rate to Return to Pre-RSV Infection Status | Participant 5 | 71.3 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for Respiratory Rate to Return to Pre-RSV Infection Status | Participant 6 | 646.4 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for Respiratory Rate to Return to Pre-RSV Infection Status | Participant 7 | 0 Hours |
Secondary
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
Population: Population included randomized or treated set. As study was terminated early with fewer participants than planned, data was not summarized. Hence, individual data for each participant was reported. Here, n (number analyzed) signifies specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time for SpO2 to Return to Pre-RSV Infection Status | Participant 1 | 0 Hours |
| Placebo | Time for SpO2 to Return to Pre-RSV Infection Status | Participant 2 | 0 Hours |
| Placebo | Time for SpO2 to Return to Pre-RSV Infection Status | Participant 3 | 70 Hours |
| Lumicitabine 40/20 mg/kg LD/MD | Time for SpO2 to Return to Pre-RSV Infection Status | Participant 4 | 33.7 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for SpO2 to Return to Pre-RSV Infection Status | Participant 5 | 0 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for SpO2 to Return to Pre-RSV Infection Status | Participant 6 | 0 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time for SpO2 to Return to Pre-RSV Infection Status | Participant 7 | 0 Hours |
Secondary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: Population included randomized or treated set. Due to early study termination and less number of participants collected data was not summarized. Hence, individual data for each participant was reported. Here, n (number analyzed) signifies specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to Clinical Stability | Participant 3 | 191.2 Hours |
| Placebo | Time to Clinical Stability | Participant 1 | 63.8 Hours |
| Placebo | Time to Clinical Stability | Participant 2 | 39.5 Hours |
| Lumicitabine 40/20 mg/kg LD/MD | Time to Clinical Stability | Participant 4 | 63.3 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time to Clinical Stability | Participant 5 | 71.3 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time to Clinical Stability | Participant 6 | 646.4 Hours |
| Lumicitabine 60/40 mg/kg LD/MD | Time to Clinical Stability | Participant 7 | 0 Hours |
Secondary
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
Population: Population included randomized or treated set who received supplemental oxygen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to no Longer Requiring Supplemental Oxygen | 59.4 Hours |
| Lumicitabine 40/20 mg/kg LD/MD | Time to no Longer Requiring Supplemental Oxygen | 0.5 Hours |
Secondary
Time To Peak Viral Load
Time to peak viral load was reported.
Time frame: Up to 28 days
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: As study was terminated early with fewer participants than planned, data for this outcome measure was not collected and analyzed.
Secondary
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
Population: ITT set was defined as all randomized participants who receive at least 1 dose of study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 | 91.16 ng/ml | — |
| Placebo | Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 5 | 189.8 ng/ml | — |
| Lumicitabine 40/20 mg/kg LD/MD | Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 1 | 187.8 ng/ml | Standard Deviation 52.97 |
| Lumicitabine 40/20 mg/kg LD/MD | Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine) | Day 5 | 358.3 ng/ml | Standard Deviation 37.42 |