A Study of Rilematovir (JNJ-53718678) in Adult Outpatients With Respiratory Syncytial Virus (RSV) Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of rilematovir compared to placebo with respect to the time to resolution of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) symptoms.

Detailed Description
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Rilematovir is an investigational RSV specific fusion inhibitor currently in development for the treatment of RSV infection in both adult and pediatric populations. The study will include a Screening period (Day -1 to Day 1), a Treatment period (Day 1 to Day 7/8 [depending on timing of first dose]), and a Follow-up period (Day 8/9 to Day 35). The total study duration of the study for each participant will be up to 35 days. The study will evaluate efficacy and safety of RSV in adult outpatients (18-85 years) who are at high risk of RSV related disease progression and have at least moderate RSV disease. The efficacy assessments include evaluation with electronic patient-reported outcome (ePRO) and the safety assessments include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events.

Official Title
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A Phase 2b Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rilematovir (JNJ-53718678) in Adult Outpatients With Respiratory Syncytial Virus (RSV) Infection Who Are at High Risk for RSV-related Disease Progression

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Drug: Rilematovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presented to the healthcare facility with symptoms suggestive of a diagnosis of acute respiratory syncytial virus (RSV) infection Has at least 2 symptoms of lower respiratory tract disease (LRTD), one of which must be scored as at least 'moderate' if the symptoms did not pre-exist before RSV onset, or one of which is scored worse than usual if the symptoms pre-existed Tested positive for RSV infection using a molecular-based diagnostic assay (polymerase chain reaction [PCR] or other) on a bilateral nasal mid-turbinate swab sample Has at least one of the following high-risk conditions that predispose them to RSV-related disease progression: a. age greater than or equal to (>=) 65 years, b. congestive heart failure (CHF), c. chronic obstructive pulmonary disease (COPD), d. asthma Randomized to study intervention treatment within 72 hours after onset of any of the RSV symptoms or worsening of pre-existing symptoms Not be hospitalized during screening (emergency room or hospital observation status for an anticipated duration of less than [<] 24 hours are not considered as hospitalization) Exclusion Criteria: Known allergies, hypersensitivity, or intolerance to rilematovir or to any of the excipients of rilematovir or placebo formulation Presence of clinically significant heart arrhythmias, uncontrolled, unstable atrial arrhythmia, or sustained ventricular arrhythmia Participant has known or suspected (from medical history or participant examination) chronic or acute hepatitis B or C infection Immunocompromised conditions Living in institutional care or assisted living facility and also receiving acute care management for any respiratory condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Rilematovir<br>Participants will receive oral dose of rilematovir 250 milligrams (mg), twice daily (bid) for 7 days. | Drug: Rilematovir<br>* Rilematovir 250 mg will be administered orally.<br>* Other names: JNJ-53718678;|
| Placebo Comparator: Treatment B: Placebo<br>Participants will receive oral dose of placebo matching to rilematovir, bid for 7 days. | Drug: Placebo<br>* Placebo matching to rilematovir will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD) Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Score at Baseline | RSV LRTD symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the RiiQ symptom scale score at baseline were reported. The RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The LRTD symptom score was calculated as the mean of the LRTD symptom scores. | Baseline | 
| Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD) Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Score at Day 3 | RSV LRTD symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the RiiQ symptom scale score at Day 3 were reported. The RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The LRTD symptom score was calculated as the mean of the LRTD symptom scores. In this outcome measure, only those individual participants who had data were reported. | Day 3 | 
| Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD) Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Score at Day 8 | RSV LRTD symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the RiiQ symptom scale score at Day 8 were reported. The RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The LRTD symptom score was calculated as the mean of the LRTD symptom scores. In this outcome measure, only those individual participants who had data were reported. | Day 8 | 
| Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD) Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Score at Day 14 | RSV LRTD symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the RiiQ symptom scale score at Day 14 were reported. The RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The LRTD symptom score was calculated as the mean of the LRTD symptom scores. In this outcome measure, only those individual participants who had data were reported. | Day 14 | 
| Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD) Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Score at Day 21 | RSV LRTD symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the RiiQ symptom scale score at Day 21 were reported. The RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The LRTD symptom score was calculated as the mean of the LRTD symptom scores. In this outcome measure, only those individual participants who had data were reported. | Day 21 | 
| Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD) Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Score at Day 28 | RSV LRTD symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the RiiQ symptom scale score at Day 28 were reported. The RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The LRTD symptom score was calculated as the mean of the LRTD symptom scores. In this outcome measure, only those individual participants who had data were reported. | Day 28 | 
| Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD) Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Score at Day 35 | RSV LRTD symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the RiiQ symptom scale score at Day 35 were reported. The RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The LRTD symptom score was calculated as the mean of the LRTD symptom scores. In this outcome measure, only those individual participants who had data were reported. | Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Post-Baseline RSV-related Complications | RSV-related complications were reported. The RSV-related complications included pulmonary complications (primary viral pneumonia, bronchitis, respiratory failure, secondary bacterial pneumonia, and exacerbations of underlying chronic pulmonary diseases [such as COPD and asthma]) and extrapulmonary complications (cardiovascular and cerebrovascular disease events, congestive heart failure [CHF] or exacerbation of underlying CHF, acute exacerbation of chronic kidney disease, severe dehydration, decompensation of previously controlled diabetes mellitus, and other airway infections). Complications after first intake of study drug were considered for this outcome measure. | Up to Day 35 | 
| Percentage of Participants With New Antibiotic Use, or New Use or Increased Dose of Systemic or Inhaled Corticosteroids and Bronchodilator, or Home Oxygen Supplementation | New antibiotic use, or new use or increased dose of systemic or inhaled corticosteroids and bronchodilators, or home oxygen supplementation were reported. | Up to Day 35 | 
| Percentage of Participants With Unscheduled Outpatient Clinic Visits, Emergency Room Visits or Hospitalization for Respiratory Infection | Unscheduled outpatient clinic visits, emergency room visits or hospitalization for respiratory infection were reported. | Up to Day 35 | 
| Percentage of Participants Meeting a Composite Endpoint of Either Developing RSV-Related Complications and/or Needing RSV-related Medical Attendance | Percentage of participants meeting a composite endpoint of either developing RSV-related complications (pulmonary and extra-pulmonary) and/or needing RSV-related medical attendance was derived. | Up to Day 35 | 
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse events (AEs) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Any AE which occurred at or after the initial administration of study intervention through the end of the study (that is, Day 35) was considered treatment-emergent. | Up to Day 35 | 
| Percentage of Participants With Treatment-emergent Abnormal Clinical Laboratory Findings | Abnormal clinical laboratory findings were reported. Laboratory abnormalities were determined as per division of microbiology and infectious diseases(DMID) toxicity as Grade 1:mild(transient or mild discomfort [less than {<} 48 hours]; no medical intervention/therapy required); Grade 2:moderate (mild to moderate limitation in activity-some assistance may be needed; no or minimal medical intervention/therapy required); Grade 3:severe (severe marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible); Grade 4:life-threatening (extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable). Only Grade 2 abnormalities are reported in this outcome measure. A treatment emergent abnormality is any abnormality not present at baseline and occurring post first administration or worsening versus baseline post first administration. | Up to Day 35 | 
| Percentage of Participants With Treatment-emergent Abnormalities in Electrocardiograms (ECGs) | Various ECG variables assessed were heart rate: abnormally low (less than or equal to [<=] 45 beats per minute [bpm]), abnormally high (greater than or equal to [>=] 120 bpm); PR interval: abnormally high (>=210 milliseconds [msec]); QRS interval: abnormally high (>=120 msec); QTc: borderline prolonged: >450 msec and <=480 msec, prolonged: >480 msec and <=500 msec, pathologicaly prolonged: >500 msec. A treatment emergent abnormality is any abnormality not present at baseline and occurring post first administration or worsening versus baseline post first administration. | Up to Day 35 | 
| Percentage of Participants With Treatment-emergent Abnormal Vital Signs Findings | Abnormal vital parameters included pulse rate: abnormally low <=45 bpm, abnormally high >=120 bpm; Systolic Blood Pressure (SBP): abnormally low <=90 millimeter of mercury (mmHg), Grade 1 (mild): >140 mmHg to <160 mmHg, Grade 2 (moderate): >=160 mmHg to <180 mmHg, Grade 3 (severe): >=180 mmHg; Diastolic BP: abnormally low <=50 mmHg, Grade 1: >90 mmHg to <100 mmHg, Grade 2: >=100 mmHg to <110 mmHg, Grade 3: >=110 mmHg; Respiratory rate: Grade 1 (mild): 17-20 breaths per minute, Grade 2 (moderate): 21-25 breaths per minute, Grade 3 (severe): >25 breaths per minute, Grade 4 (potentially life threatening): intubation; Oxygen saturation: abnormally low: <95%; Temperature: abnormally high >38.0 degree celsius. A treatment emergent abnormality is any abnormality not present at baseline and occurring post first administration or worsening versus baseline post first administration. | Up to Day 35 | 
| RSV Viral Load Over Time | RSV viral load (subtype: RSV A and RSV B) was measured over time by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the nasal swab specimens collected at the clinic visits and at home. In this outcome measure, only those timepoints and RSV subtypes (A or B) for which individual participants had data were reported. | Baseline, Days 3, 5, 8, 15, and 21 | 
| Plasma Concentration of Rilematovir | Plasma concentration of rilematovir was reported. This outcome measure was planned to be analyzed for specified arm only. In this outcome measure, only those timepoints for which individual participants had data were reported. | Day 1: 1 hour post dose, Day 3: pre-dose and 1 hour post dose, and Follow-up: Day 8 |