Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Oral Lumicitabine Regimens in Hospitalized Adult Participants Infected With Human Metapneumovirus

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Number of participants with an abnormal physical examination will be reported. A complete physical examination (including all body systems, height [only at screening], and body weight measurement) or a directed physical examination including respiratory system, nose, ear, throat, facial and neck lymph nodes, and skin examination will be performed.

Number of participants with abnormal vital signs (including body temperature, heart rate, respiratory rate, systolic blood pressure [SBP], diastolic blood pressure [DBP]), and SpO2 measurements will be reported.

Number of participants with abnormal twelve-lead ECG will be reported.

Number of participants with clinical laboratory abnormalities (clinical laboratory tests include the following: hematology panel, serum chemistry panel, urinalysis, estimated glomerular filtration rate (GFR), urine pregnancy test (women only), and serum procalcitonin levels) will be reported.

The Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolite of lumicitabine.

The C12h is the predicted concentration of JNJ-63549109 at 12 hours postdose.

AUC is defined as area under plasma concentration-time curve.

The ordinal scale will be used to assess participant's status and consists of 6 categories that are exhaustive, mutually exclusive, and ordered, where: 1) Death, 2) Admitted to intensive care unit (ICU), 3) Non-ICU hospitalization requiring supplemental oxygen, 4) Non-ICU hospitalization not requiring supplemental oxygen, 5) Not hospitalized, unable to resume normal activities, 6) Not hospitalized, resumption of normal activities.

The length of hospital stay from admission to discharge will be reported.

The length of hospital stay from admission to readiness for discharge will be reported.

The length of hospital stay from study treatment initiation to discharge will be reported.

The length of hospital stay from study treatment initiation to readiness for discharge will be reported.

The percentage of enrolled participants requiring admission to the ICU will be reported.

In the event that a participant requires admission to the ICU, the duration for how long the participant remained in the ICU will be measured.

The percentage of enrolled participants requiring oxygen supplementation/noninvasive mechanical ventilation support (for example [eg], nasal cannula, face mask, continuous positive airway pressure, bilevel positive airway pressure) above pre-hMPV infection status will be reported.

The duration of oxygen supplementation/noninvasive mechanical ventilation support (eg, nasal cannula, face mask, continuous positive airway pressure, bilevel positive airway pressure) above pre-hMPV infection status will be measured.

The percentage of enrolled participants requiring invasive mechanical ventilation support (eg, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) above pre-hMPV infection status will be reported.

The duration of invasive mechanical ventilation support (eg, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) above pre-hMPV infection status will be measured.

The time to which a participant no longer requires supplemental oxygen will be measured.

Time to clinical stability is defined as the time at which the following criteria are all met: normalization of blood oxygen level (return to baseline; by pulse oximetry) without requirement of supplemental oxygen beyond baseline level, normalization of oral feeding, normalization of respiratory rate and normalization of heart rate.

The number of hours until SpO2 is >= 93% on room air among participants who were not on supplemental oxygen prior to onset of respiratory symptoms will be recorded.

The time for respiratory rate to return to pre-hMPV infection status will be recorded.

The time for SpO2 to return to pre-hMPV infection status will be recorded.

The time for body temperature to return to pre-hMPV infection status will be recorded.

The percentage of enrolled participants who require hydration and/or feeding by intravenous (IV) catheter or nasogastric tube will be reported.

The number of participants with bacterial superinfections, as defined by the investigator based on clinical judgment and/or increasing procalcitonin levels, reported as AEs will be reported.

The number of participants with treatment-emergent complications, including cardiovascular events and cerebrovascular events (for example, myocardial infarction, congestive heart failure exacerbation, arrhythmia, stroke) or Clostridium difficile-associated diarrhea, will be reported.

The NEWS scoring system measures acute-illness severity using 7 physiological parameters (respiration rate, oxygen saturation, supplementary oxygen requirement, temperature, systolic blood pressure, heart rate, and level of consciousness). Each parameter is scored between 0 and 3 compared to normal ranges, with higher scores indicating greater severity. The total score is the sum of the individual physiological parameter values and ranges between 0 (least severe) and 21 (most severe).

Number of participants will be assessed for all-cause mortality.

Katz activities of daily living will assess questions related to Bathing, Dressing, Toileting, Transferring, Continence and Feeding. For the six individual activities, a score of 1 indicates independence, and a score of 0 indicates dependence. Total score will be calculated by adding the scores of all six activities and ranges from 0 high (participant independent) to 6 low (participant very dependent).

Viral load over time will be measured in mid-turbinate nasal swabs (obtained from non-intubated participants) or in mid-turbinate nasal swabs and endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) by qRT-PCR.

Peak viral load over time will be measured by qRT-PCR.

Time to peak viral load as measured by qRT-PCR will be reported.

Rate of decline in hMPV viral load during treatment as measured by qRT-PCR will be reported.

Time to hMPV RNA being undetectable as measured by qRT-PCR.

Percentage of participants with undetectable viral load at each time point will be reported.

The AUC of hMPV RNA log10 viral load (measured by 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.

The AUC of hMPV RNA log10 viral load (measured by 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.

If dosing duration is increased by the Independent Data Monitoring Committee (IDMC), the AUC of hMPV viral load (measured by qRT-PCR in the mid-turbinate nasal swab specimens) will be estimated by analyzing mean log10 viral load values over time using a restricted maximum likelihood based repeated measures approach.

Number of participants will be assessed for postbaseline changes in the hMPV polymerase Lgene (only if no mutations are seen in the Lgene) and other regions of the hMPV genome compared with baseline sequences.