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

Phase 2

Terminated

Conditions: Respiratory Syncytial Virus

Interventions: Drug: Placebo
Drug: Rilematovir

Registration Number: NCT04978337

Lead Sponsor: Janssen Research & Development, LLC

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment B: Placebo	Placebo	Participants will receive oral dose of placebo matching to rilematovir, bid for 7 days.
Treatment A: Rilematovir	Rilematovir	Participants will receive oral dose of rilematovir 250 milligrams (mg), twice daily (bid) for 7 days.

Primary Outcome Measures

Name	Time	Method
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	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.
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	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.
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	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.
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	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.
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	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.
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	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.
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	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Post-Baseline RSV-related Complications	Up to Day 35	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.
Percentage of Participants Meeting a Composite Endpoint of Either Developing RSV-Related Complications and/or Needing RSV-related Medical Attendance	Up to Day 35	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.
Percentage of Participants With Treatment-emergent Abnormalities in Electrocardiograms (ECGs)	Up to Day 35	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.
RSV Viral Load Over Time	Baseline, Days 3, 5, 8, 15, and 21	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.
Percentage of Participants With Unscheduled Outpatient Clinic Visits, Emergency Room Visits or Hospitalization for Respiratory Infection	Up to Day 35	Unscheduled outpatient clinic visits, emergency room visits or hospitalization for respiratory infection were reported.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to Day 35	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.
Percentage of Participants With New Antibiotic Use, or New Use or Increased Dose of Systemic or Inhaled Corticosteroids and Bronchodilator, or Home Oxygen Supplementation	Up to Day 35	New antibiotic use, or new use or increased dose of systemic or inhaled corticosteroids and bronchodilators, or home oxygen supplementation were reported.
Percentage of Participants With Treatment-emergent Abnormal Clinical Laboratory Findings	Up to Day 35	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.
Percentage of Participants With Treatment-emergent Abnormal Vital Signs Findings	Up to Day 35	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.
Plasma Concentration of Rilematovir	Day 1: 1 hour post dose, Day 3: pre-dose and 1 hour post dose, and Follow-up: Day 8	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.

Trial Locations

Locations (84): Central Alabama Research
🇺🇸
Birmingham, Alabama, United States
Fiel Family and Sports Medicine Clinical Research Advantage
🇺🇸
Tempe, Arizona, United States
IMD Clinical Trials
🇺🇸
Bakersfield, California, United States
Hope clinical Research LLC
🇺🇸
Canoga Park, California, United States
Peninsula Research Associates
🇺🇸
Rolling Hills Estates, California, United States
Bensch Clinical Research, LLC
🇺🇸
Stockton, California, United States
New Life Medical Research Center, Inc.
🇺🇸
Hialeah, Florida, United States
Best Quality Research Inc
🇺🇸
Hialeah, Florida, United States
Homestead Associates in Research, Inc
🇺🇸
Homestead, Florida, United States
Care Partners Clinical Research
🇺🇸
Jacksonville, Florida, United States
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Central Alabama Research
🇺🇸Birmingham, Alabama, United States