Back to resultsStudy to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine Regimens in Adult Participants Hospitalized With Respiratory Syncytial Virus
Primary Purpose
Respiratory Syncytial Viruses
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
lumicitabine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Respiratory Syncytial Viruses
Eligibility Criteria
Inclusion Criteria:
- 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
- Diagnosed with respiratory syncytial virus (RSV) infection based on polymerase chain reaction (PCR)-based assay with or without co infection with another respiratory pathogen (eg, influenza, human metapneumovirus, or bacteria)
- With the exception of the RSV disease, medically stable on the basis of medical history, physical examination, 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 RSV infection. This determination must be recorded in the participant's source documents and initialed by the investigator
- A woman must have a negative urine beta human chorionic gonadotropin at screening
- A woman must agree not to donate eggs (ova, oocytes) during the study and for at least 44 days after receiving the last dose of study drug
- Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies A woman must be of non-childbearing potential defined as either: a) Postmenopausal: a postmenopausal state is defined as more than (>) 45 years and no menses for 12 consecutive months without an alternative medical cause, OR Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy. b) Of childbearing potential and, if heterosexually active, also included: practicing a highly effective method of contraception (failure rate of less than (<) 1percent (%) per year when used consistently and correctly)
- Participants must have a body weight of at least 50.0 kilogram, at screening
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 are considered by the investigator to be immuno-compromised within the past 12 months, whether due to underlying medical condition (example, malignancy or genetic disorder) or medical therapy (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 with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis
- 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 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table: Hemoglobin <9.5 gram per deciliter (g/dL), Platelet count <75,000 per millimeter cube (/mm^³), White blood cell count <1,000/mm^³, Absolute neutrophil count <1,000/mm^³
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Regimen A (Placebo)
Regimen B (low-dose lumicitabine)
Regimen C (High-dose lumicitabine)
Arm Description
Participants of part 1 and part 2 will receive a single loading dose (LD) (Dose 1) followed by 9 maintenance doses (MDs) (Doses 2 to 10) of matching placebo, administered twice daily.
Participants of part 1 and part 2 will receive a single 750 mg LD (Dose 1) followed by nine 250 mg MDs (Doses 2 to 10) of lumicitabine, administered twice daily.
Participants of part 2 will receive a single 1000 mg LD (Dose 1) followed by nine 500 mg MDs (Doses 2 to 10) of lumicitabine, administered twice daily.
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1
Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5
Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1
AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5
AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1
Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5
Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7])
RSV RNA viral load in log10 copies/milliliter/day (log10 copies/mL/day) was measured in mid-turbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Due to early termination of study, the analysis was not conducted as planned. Instead, using the same specification as for the primary analysis, a comparison was made on the AUC(1-7) days of pooled active treatment groups versus pooled placebo. The comparison was done as planned using a mixed model for repeated measures, using all available viral load data of baseline up to and including Day 7. The model computes the AUC at group level based on all available data, taking missing data into account under the missing at random assumption. The table reports the planned difference versus (pooled) placebo. No adjustment for multiplicity was applied.
Secondary Outcome Measures
Number of Participants With Adverse Events (AEs)
An 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.
Number of Participants With Vital Sign Abnormalities
Number of participants with vital sign (systolic and diastolic blood pressure [BP], pulse rate, respiratory rate, temperature and oxygen saturation) abnormalities were reported. For systolic BP: abnormally low refers to less than or equal to (<=) 90 millimeter of mercury (mmHg); for diastolic BP: abnormally low refers to <= 50 mmHg; for pulse rate abnormally low refers to less than (<) 45 beats per minutes (bpm) and abnormally high refers to greater than or equal to (>=) 120 bpm; for temperature in degree Celsius abnormally high refers to greater than (>) 37.8 (tympanic), >38.0 (forehead), >38.0 (oral), >37.2 (rectal), >38.0 (axillary); for oxygen saturation in percentage (%) abnormally low refers to < 95. Grade 1 = mild; grade 2 = moderate; grade 3 = severe.
Number of Participants With QT Interval Abnormalities
Number of participants with QT interval abnormalities (prolonged) were reported.
Number of Participants With Clinical Laboratory Abnormalities
Number of participants with clinical laboratory (serum chemistry and hematology) abnormalities were reported. Abbreviations; Erythrocyte MCHC = Erythrocyte Mean Corpuscular Hemoglobin Concentration; Erythrocyte MCH = Erythrocyte Mean Corpuscular Hemoglobin; Ery. = Erythrocyte
Time of Hospital Stay From Study Treatment Initiation to Discharge
It is the time from treatment initiation to hospital discharge in hours.
Time of Hospital Stay From Admission to Discharge
It is the time from hospital admission to hospital discharge in hours.
Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge
It is the time from study treatment initiation to readiness for discharge in hours, with readiness for discharge defined by the investigator.
Time of Hospital Stay From Admission to Readiness for Discharge
It is the time from hospital admission to readiness for discharge in hours, with readiness for discharge defined by the investigator.
Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment
Number of participants who required to be admitted to the ICU since initiation of treatment were reported.
Duration of Intensive Care Unit Stay
In the event that a participant required ICU since initiation of treatment, the duration for how long the participant remained in the ICU was measured.
Number of Participants Who Required Supplemental Oxygen
Number of participants who required supplemental oxygen were reported.
Time to End of Oxygen Supplementation
It is the time from first dose of study drug to the last end date and time of any oxygen supplementation in hours.
Time (Number of Hours) 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 the Onset of Respiratory Symptoms
Time (number of hours) until SpO2 >= 93% on room air among participants who were not on supplemental oxygen prior to the onset of respiratory symptoms was reported.
Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate
It is the time from first dose of study drug until the time to return to pre-RSV disease level for respiratory rate. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time to Return to Pre-RSV Disease Level for Oxygen Saturation
It is the time from first dose of study drug until the time to return to pre-RSV disease level for oxygen saturation. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time to Return to Pre-RSV Disease Level for Body Temperature
It is the time from first dose of study drug until the time to return to pre-RSV disease level for body temperature. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Number of Participants Who Required Noninvasive Mechanical Ventilation Support
Number of participants who required noninvasive mechanical ventilation support (that is supplemental oxygen [excluding mechanical ventilation]) were reported.
Time to End of Noninvasive Mechanical Ventilation Support
It is the time from first dose of study drug to the last end date and time of noninvasive mechanical ventilation support in hours.
Number of Participants Who Required Invasive Mechanical Ventilation Support
Number of participants who required invasive mechanical ventilation support were reported.
Time to End of Invasive Mechanical Ventilation Support
It is the time from first dose of study drug to the last end date and time of invasive mechanical ventilation support in hours.
Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score
It is the time from first dose of study drug until the time to return to pre-RSV functional status. Functional status is the total points on the KATZ index of independence in activities of daily living (KATZ ADL score). Katz activities of daily living assessed questions related to bathing, dressing, toileting, transferring, continence and feeding components. Total score was calculated by adding the scores for all 6 activities which ranges from 0 high (participant independent) to 6 low (participant very dependent). If one or more component was missing, then the KATZ ADL score was not calculated. The return to pre-RSV functional status occurs at the timepoint where for the first time the KATZ ADL score is equal or higher than the pre-RSV KATZ ADL score and after which no scores lower than the pre-RSV KATZ ADL score occur anymore.
Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube
Number of participants who required hydration or feeding by IV catheter or nasogastric tube were reported.
Time to Clinical Stability
Time to clinical stability is defined as the time from first dose of study drug until the time at which the following criteria were 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.
Number of Participants in Each Ordinal Scale Category
Number of participants in each ordinal scale category were reported. Ordinal scale consists of 6 categories or clinical states that are exhaustive, mutually exclusive, and ordered: category 1) death; category 2) admitted to ICU; category 3) non-ICU hospitalization requiring supplemental oxygen; category 4) non-ICU hospitalization not requiring supplemental oxygen; category 5) not hospitalized, unable to resume normal activities; category 6) not hospitalized, resumption of normal activities.
Number of Participants With All-Cause Mortality
All-cause mortality included all deaths of participants due to any cause.
RSV RNA Viral Load Over Time
Antiviral activity RSV RNA viral load was 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) using qRT-PCR performed at the central laboratory.
Peak Viral Load
Peak Viral load is the highest value of log10 viral load at or after the baseline measurement. Peak viral load over time was measured by qRT-PCR.
Time to Peak Viral Load
Time to peak viral load is the time from initiation of study treatment until the first time point with the peak viral load.
Rate of Decline of Viral Load
Rate of decline of viral load over the first 24 hours calculated as a log decline/24 hours defined as: 24-hour log viral load after first dose of study drug minus (-) log viral load at baseline divided by (/) date/time of 24-hour viral load sample - date/time of baseline viral load.
Time to RSV RNA Viral Load Being Undetectable
It is the time in hours from initiation of study treatment until the first post baseline time point at which the virus is undetectable in an assessment and after which time no detectable virus assessment follows as measured by qRT-PCR.
Number of Participants With Undetectable Viral Load
Number of participants with undetectable viral load up to 28 days were reported.
RSV RNA Viral Load AUC up to Day 14
RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling.
RSV RNA Viral Load AUC in Participants Assigned to a Longer Dosing Duration
RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling.
Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences
Number of participants with postbaseline changes in the RSV polymerase L gene and other regions of the RSV genome compared with baseline sequences were reported.
Full Information
NCT ID
NCT02935673
First Posted
October 14, 2016
Last Updated
December 23, 2019
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02935673
Brief Title
Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine Regimens in Adult Participants Hospitalized With Respiratory Syncytial Virus
Official Title
A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine Regimens in Adult Subjects Hospitalized With Respiratory Syncytial Virus
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Why Stopped
sponsor decision
Study Start Date
October 25, 2016 (Actual)
Primary Completion Date
July 17, 2018 (Actual)
Study Completion Date
July 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to characterize the Pharmacokinetic and to confirm the popPK model derived from healthy volunteers in hospitalized adults who are infected with respiratory syncytial virus (RSV) and to determine in adults who are hospitalized with respiratory syncytial virus (RSV) infection 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) assay.
Detailed Description
The study will be conducted in 3 phases: a screening phase, a treatment phase from Day 1 to Day 5/6 (depending on the timing of the loading dose), and a follow-up phase for a total of 28 days post randomization. Participants will have assessments completed at Day 7, Day 10, Day 14, and Day 28. Depending on discharge date, assessments will be completed either while hospitalized or during outpatient visits. The duration of the participant's participation will be approximately 28 days. The study will be performed in 2 parts. Participants will be randomly assigned to one of 2 treatment groups in part 1, and to one of 3 treatment groups in part 2. Treatment groups will be evaluated for PK and safety after a target of approximately 24 participants have been enrolled in part 1 and before initiating part 2 (approximately 90 participants in part 2). An Independent Data Monitoring Committee (IDMC) will be established to monitor the safety of participants and will review data in an unblinded manner on a regular basis to ensure the continuing safety of the participants enrolled in this study and to evaluate whether efficacy objectives are met. The committee will meet periodically to review interim data. Based on the recommendations of the IDMC following interim analyses/reviews, an increase in duration may be implemented.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Syncytial Viruses
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Regimen A (Placebo)
Arm Type
Experimental
Arm Description
Participants of part 1 and part 2 will receive a single loading dose (LD) (Dose 1) followed by 9 maintenance doses (MDs) (Doses 2 to 10) of matching placebo, administered twice daily.
Arm Title
Regimen B (low-dose lumicitabine)
Arm Type
Experimental
Arm Description
Participants of part 1 and part 2 will receive a single 750 mg LD (Dose 1) followed by nine 250 mg MDs (Doses 2 to 10) of lumicitabine, administered twice daily.
Arm Title
Regimen C (High-dose lumicitabine)
Arm Type
Experimental
Arm Description
Participants of part 2 will receive a single 1000 mg LD (Dose 1) followed by nine 500 mg MDs (Doses 2 to 10) of lumicitabine, administered twice daily.
Intervention Type
Drug
Intervention Name(s)
lumicitabine
Other Intervention Name(s)
ALS-8176/JNJ-64041575
Intervention Description
Oral administration of lumicitabine as tablet.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral administration of matching placebo.
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 1
Description
Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time Frame
Day 1
Title
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 at Day 5
Description
Cmax is the maximum observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time Frame
Day 5
Title
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 1
Description
AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time Frame
Day 1
Title
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24h]) of JNJ-63549109 at Day 5
Description
AUC(0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours after dosing of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time Frame
Day 5
Title
Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 1
Description
Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time Frame
Day 1
Title
Trough Observed Plasma Concentration (Ctrough) of JNJ-63549109 at Day 5
Description
Ctrough is the trough observed plasma concentration of JNJ-63549109. JNJ-63549109 is the metabolized product of lumicitabine.
Time Frame
Day 5
Title
Least Square Mean Difference (Low and High Dose Lumicitabine Versus Placebo) of Respiratory Syncytial Virus (RSV) Ribonucleic Acid (RNA) Viral Load Area Under the Concentration-time Curve From Day 1 to 7 (AUC[1-7])
Description
RSV RNA viral load in log10 copies/milliliter/day (log10 copies/mL/day) was measured in mid-turbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling methods) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Due to early termination of study, the analysis was not conducted as planned. Instead, using the same specification as for the primary analysis, a comparison was made on the AUC(1-7) days of pooled active treatment groups versus pooled placebo. The comparison was done as planned using a mixed model for repeated measures, using all available viral load data of baseline up to and including Day 7. The model computes the AUC at group level based on all available data, taking missing data into account under the missing at random assumption. The table reports the planned difference versus (pooled) placebo. No adjustment for multiplicity was applied.
Time Frame
Day 1 (Baseline) to 7
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
An 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.
Time Frame
Up to 28 Days
Title
Number of Participants With Vital Sign Abnormalities
Description
Number of participants with vital sign (systolic and diastolic blood pressure [BP], pulse rate, respiratory rate, temperature and oxygen saturation) abnormalities were reported. For systolic BP: abnormally low refers to less than or equal to (<=) 90 millimeter of mercury (mmHg); for diastolic BP: abnormally low refers to <= 50 mmHg; for pulse rate abnormally low refers to less than (<) 45 beats per minutes (bpm) and abnormally high refers to greater than or equal to (>=) 120 bpm; for temperature in degree Celsius abnormally high refers to greater than (>) 37.8 (tympanic), >38.0 (forehead), >38.0 (oral), >37.2 (rectal), >38.0 (axillary); for oxygen saturation in percentage (%) abnormally low refers to < 95. Grade 1 = mild; grade 2 = moderate; grade 3 = severe.
Time Frame
Up to 28 Days
Title
Number of Participants With QT Interval Abnormalities
Description
Number of participants with QT interval abnormalities (prolonged) were reported.
Time Frame
Up to 28 Days
Title
Number of Participants With Clinical Laboratory Abnormalities
Description
Number of participants with clinical laboratory (serum chemistry and hematology) abnormalities were reported. Abbreviations; Erythrocyte MCHC = Erythrocyte Mean Corpuscular Hemoglobin Concentration; Erythrocyte MCH = Erythrocyte Mean Corpuscular Hemoglobin; Ery. = Erythrocyte
Time Frame
Up to 28 Days
Title
Time of Hospital Stay From Study Treatment Initiation to Discharge
Description
It is the time from treatment initiation to hospital discharge in hours.
Time Frame
From study treatment initiation to discharge (Up to 28 Days)
Title
Time of Hospital Stay From Admission to Discharge
Description
It is the time from hospital admission to hospital discharge in hours.
Time Frame
From admission to discharge (Up to 28 Days)
Title
Time of Hospital Stay From Study Treatment Initiation to Readiness for Discharge
Description
It is the time from study treatment initiation to readiness for discharge in hours, with readiness for discharge defined by the investigator.
Time Frame
From study treatment initiation to readiness for discharge on Day 2 or up to Day 6 if hospitalization is prolonged
Title
Time of Hospital Stay From Admission to Readiness for Discharge
Description
It is the time from hospital admission to readiness for discharge in hours, with readiness for discharge defined by the investigator.
Time Frame
Up to 28 Days
Title
Number of Participants Who Required to be Admitted to the Intensive Care Unit (ICU) Since Initiation of Treatment
Description
Number of participants who required to be admitted to the ICU since initiation of treatment were reported.
Time Frame
Up to 28 Days
Title
Duration of Intensive Care Unit Stay
Description
In the event that a participant required ICU since initiation of treatment, the duration for how long the participant remained in the ICU was measured.
Time Frame
Up to 28 Days
Title
Number of Participants Who Required Supplemental Oxygen
Description
Number of participants who required supplemental oxygen were reported.
Time Frame
Up to 28 Days
Title
Time to End of Oxygen Supplementation
Description
It is the time from first dose of study drug to the last end date and time of any oxygen supplementation in hours.
Time Frame
Up to 28 Days
Title
Time (Number of Hours) 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 the Onset of Respiratory Symptoms
Description
Time (number of hours) 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
Title
Time to Return to Pre-respiratory Syncytial Virus (Pre-RSV) Disease Level for Respiratory Rate
Description
It is the time from first dose of study drug until the time to return to pre-RSV disease level for respiratory rate. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time Frame
Up to 28 Days
Title
Time to Return to Pre-RSV Disease Level for Oxygen Saturation
Description
It is the time from first dose of study drug until the time to return to pre-RSV disease level for oxygen saturation. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time Frame
Up to 28 Days
Title
Time to Return to Pre-RSV Disease Level for Body Temperature
Description
It is the time from first dose of study drug until the time to return to pre-RSV disease level for body temperature. The return to pre-RSV disease level occurred when the observed value of the parameter was indicated by the investigator as normal, and no later observed values were indicated by the investigator as abnormal.
Time Frame
Up to 28 Days
Title
Number of Participants Who Required Noninvasive Mechanical Ventilation Support
Description
Number of participants who required noninvasive mechanical ventilation support (that is supplemental oxygen [excluding mechanical ventilation]) were reported.
Time Frame
Up to 28 Days
Title
Time to End of Noninvasive Mechanical Ventilation Support
Description
It is the time from first dose of study drug to the last end date and time of noninvasive mechanical ventilation support in hours.
Time Frame
Up to 28 Days
Title
Number of Participants Who Required Invasive Mechanical Ventilation Support
Description
Number of participants who required invasive mechanical ventilation support were reported.
Time Frame
Up to 28 Days
Title
Time to End of Invasive Mechanical Ventilation Support
Description
It is the time from first dose of study drug to the last end date and time of invasive mechanical ventilation support in hours.
Time Frame
Up to 28 Days
Title
Time to Return to Pre-RSV Functional Status as Assessed by KATZ Activities of Daily Living (ADL) Score
Description
It is the time from first dose of study drug until the time to return to pre-RSV functional status. Functional status is the total points on the KATZ index of independence in activities of daily living (KATZ ADL score). Katz activities of daily living assessed questions related to bathing, dressing, toileting, transferring, continence and feeding components. Total score was calculated by adding the scores for all 6 activities which ranges from 0 high (participant independent) to 6 low (participant very dependent). If one or more component was missing, then the KATZ ADL score was not calculated. The return to pre-RSV functional status occurs at the timepoint where for the first time the KATZ ADL score is equal or higher than the pre-RSV KATZ ADL score and after which no scores lower than the pre-RSV KATZ ADL score occur anymore.
Time Frame
Up to 28 Days
Title
Number of Participants Who Required Hydration or Feeding by Intravenous (IV) Catheter or Nasogastric Tube
Description
Number of participants who required hydration or feeding by IV catheter or nasogastric tube were reported.
Time Frame
Up to 28 Days
Title
Time to Clinical Stability
Description
Time to clinical stability is defined as the time from first dose of study drug until the time at which the following criteria were 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.
Time Frame
Up to 28 Days
Title
Number of Participants in Each Ordinal Scale Category
Description
Number of participants in each ordinal scale category were reported. Ordinal scale consists of 6 categories or clinical states that are exhaustive, mutually exclusive, and ordered: category 1) death; category 2) admitted to ICU; category 3) non-ICU hospitalization requiring supplemental oxygen; category 4) non-ICU hospitalization not requiring supplemental oxygen; category 5) not hospitalized, unable to resume normal activities; category 6) not hospitalized, resumption of normal activities.
Time Frame
Day 5/6 (Day of last study treatment)
Title
Number of Participants With All-Cause Mortality
Description
All-cause mortality included all deaths of participants due to any cause.
Time Frame
Up to 28 Days
Title
RSV RNA Viral Load Over Time
Description
Antiviral activity RSV RNA viral load was 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) using qRT-PCR performed at the central laboratory.
Time Frame
Days 2, 3, 4, 5, 6, 7, 10, 14, and 28
Title
Peak Viral Load
Description
Peak Viral load is the highest value of log10 viral load at or after the baseline measurement. Peak viral load over time was measured by qRT-PCR.
Time Frame
Up to 28 Days
Title
Time to Peak Viral Load
Description
Time to peak viral load is the time from initiation of study treatment until the first time point with the peak viral load.
Time Frame
Up to 28 Days
Title
Rate of Decline of Viral Load
Description
Rate of decline of viral load over the first 24 hours calculated as a log decline/24 hours defined as: 24-hour log viral load after first dose of study drug minus (-) log viral load at baseline divided by (/) date/time of 24-hour viral load sample - date/time of baseline viral load.
Time Frame
Up to 28 Days
Title
Time to RSV RNA Viral Load Being Undetectable
Description
It is the time in hours from initiation of study treatment until the first post baseline time point at which the virus is undetectable in an assessment and after which time no detectable virus assessment follows as measured by qRT-PCR.
Time Frame
Up to 28 Days
Title
Number of Participants With Undetectable Viral Load
Description
Number of participants with undetectable viral load up to 28 days were reported.
Time Frame
Up to 28 Days
Title
RSV RNA Viral Load AUC up to Day 14
Description
RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling.
Time Frame
Up to Day 14
Title
RSV RNA Viral Load AUC in Participants Assigned to a Longer Dosing Duration
Description
RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples (obtained from intubated participants or via suction through tracheostomy or other sampling.
Time Frame
Up to 1 Day after the last dose of study drug
Title
Number of Participants With Postbaseline Changes in the RSV Polymerase L Gene and Other Regions of the RSV Genome Compared With Baseline Sequences
Description
Number of participants with 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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Diagnosed with respiratory syncytial virus (RSV) infection based on polymerase chain reaction (PCR)-based assay with or without co infection with another respiratory pathogen (eg, influenza, human metapneumovirus, or bacteria)
With the exception of the RSV disease, medically stable on the basis of medical history, physical examination, 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 RSV infection. This determination must be recorded in the participant's source documents and initialed by the investigator
A woman must have a negative urine beta human chorionic gonadotropin at screening
A woman must agree not to donate eggs (ova, oocytes) during the study and for at least 44 days after receiving the last dose of study drug
Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies A woman must be of non-childbearing potential defined as either: a) Postmenopausal: a postmenopausal state is defined as more than (>) 45 years and no menses for 12 consecutive months without an alternative medical cause, OR Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy. b) Of childbearing potential and, if heterosexually active, also included: practicing a highly effective method of contraception (failure rate of less than (<) 1percent (%) per year when used consistently and correctly)
Participants must have a body weight of at least 50.0 kilogram, at screening
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 are considered by the investigator to be immuno-compromised within the past 12 months, whether due to underlying medical condition (example, malignancy or genetic disorder) or medical therapy (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 with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis
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 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table: Hemoglobin <9.5 gram per deciliter (g/dL), Platelet count <75,000 per millimeter cube (/mm^³), White blood cell count <1,000/mm^³, Absolute neutrophil count <1,000/mm^³
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Fresno
State/Province
California
Country
United States
City
Orange
State/Province
California
Country
United States
City
Stanford
State/Province
California
Country
United States
City
Eustis
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Butte
State/Province
Montana
Country
United States
City
Rochester
State/Province
New York
Country
United States
City
Syracuse
State/Province
New York
Country
United States
City
Bahia Blanca
Country
Argentina
City
Barrio Parque Velez Sarfield
Country
Argentina
City
Buenos Aires
Country
Argentina
City
Ciudad de Buenos Aires
Country
Argentina
City
Ciudad De La Plata
Country
Argentina
City
Cordoba
Country
Argentina
City
Córdoba
Country
Argentina
City
La Plata
Country
Argentina
City
Rosario
Country
Argentina
City
Cairns
Country
Australia
City
Geelong
Country
Australia
City
Melbourne
Country
Australia
City
South Brisbane
Country
Australia
City
Sydney
Country
Australia
City
Brugge
Country
Belgium
City
Lier
Country
Belgium
City
Belo Horizonte
Country
Brazil
City
Passo Fundo
Country
Brazil
City
Porto Alegre
Country
Brazil
City
Ribeirao Preto
Country
Brazil
City
Sao Paulo
Country
Brazil
City
Kozloduy
Country
Bulgaria
City
Petrich
Country
Bulgaria
City
Ruse
Country
Bulgaria
City
Sofia
Country
Bulgaria
City
Veliko Tarnovo
Country
Bulgaria
City
Hamilton
State/Province
Ontario
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Colombes
Country
France
City
Dijon
Country
France
City
La Tronche
Country
France
City
Limoges
Country
France
City
Lyon
Country
France
City
Morlaix
Country
France
City
Nantes
Country
France
City
Paris
Country
France
City
Poitiers
Country
France
City
Suresnes
Country
France
City
Tours
Country
France
City
Marburg
Country
Germany
City
Witten
Country
Germany
City
Fukuoka
Country
Japan
City
Fukushima
Country
Japan
City
Gifu
Country
Japan
City
Gunma
Country
Japan
City
Hamamatue
Country
Japan
City
Isahaya
Country
Japan
City
Izumo
Country
Japan
City
Kitakyusyu
Country
Japan
City
Kobe-city,
Country
Japan
City
Nagasaki
Country
Japan
City
Nagoya
Country
Japan
City
Osaka
Country
Japan
City
Ota
Country
Japan
City
Sendai
Country
Japan
City
Seto
Country
Japan
City
Shiogama
Country
Japan
City
Tanabe
Country
Japan
City
Tokai-mura
Country
Japan
City
Tokyo
Country
Japan
City
Tsu
Country
Japan
City
Uruma
Country
Japan
City
Bucheon
Country
Korea, Republic of
City
Daegu
Country
Korea, Republic of
City
Gwangju
Country
Korea, Republic of
City
Incheon
Country
Korea, Republic of
City
Seongnam
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Johor Bharu
Country
Malaysia
City
Kuala Lumpur
Country
Malaysia
City
Kuala
Country
Malaysia
City
Kuching
Country
Malaysia
City
Melaka
Country
Malaysia
City
Miri
Country
Malaysia
City
Taiping
Country
Malaysia
City
Cuernavaca
Country
Mexico
City
Guadalajara
Country
Mexico
City
Mexico
Country
Mexico
City
Monterrey
Country
Mexico
City
Leiden
Country
Netherlands
City
Utrecht
Country
Netherlands
City
Białystok
Country
Poland
City
Chęciny
Country
Poland
City
Mrozy
Country
Poland
City
Proszowice
Country
Poland
City
Elche
Country
Spain
City
Granada
Country
Spain
City
Madrid
Country
Spain
City
Santiago de Compostela
Country
Spain
City
Vigo
Country
Spain
City
Göteborg
Country
Sweden
City
Malmö
Country
Sweden
City
Umeå
Country
Sweden
City
Uppsala
Country
Sweden
City
Kaohsiung
Country
Taiwan
City
New Taipei
Country
Taiwan
City
Tainan
Country
Taiwan
City
Taipei
Country
Taiwan
City
London
Country
United Kingdom
City
Southampton
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine Regimens in Adult Participants Hospitalized With Respiratory Syncytial Virus
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