Respiratory Syncytial Virus Infection
Conditions
Brief summary
The purpose of this study is to learn about the safety and effects of sisunatovir. Sisunatovir is studied for the possible treatment of Respiratory Syncytial Virus (RSV). RSV is a virus that causes lung infections with cold-like symptoms, but it can cause severe illness in some people. Sisunatovir is studied in adults: * who are not admitted to the hospital and * who have high chances of having a severe illness from RSV infection. This study is seeking participants who: * Are confirmed to have RSV. * Have symptoms of a lung infection. * Are 18 years of age or older. * Have one or more of the following which increases the chances of RSV illness: * A long-term lung disease. * heart failure. * a condition that weakens the immune system. * Are 65 years of age or older and do not have any of the conditions above Half of the participants in this study will receive sisunatovir. The other half will receive a placebo for 5 days. Placebo looks same like the study medicine but does not have any medication. Both sisunatovir and placebo will be taken by mouth. The study will compare the experiences of people receiving sisunatovir to those of the people who do not. This will help decide if sisunatovir is safe and effective. Participants will attend about 8-10 study visits over 5 weeks. During this time, they will have: * visits at the study clinic, * blood work, * swabs of the nose, * questionnaires, * a follow-up phone call.
Interventions
DRUGSisunatovir
Participants will receive tablets from Day 1 to Day 5
DRUGPlacebo
Participants will receive matching placebo tablets from Day 1 to Day 5
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants will be assigned to receive study intervention according to the assigned treatment group from the randomization scheme. Investigators will remain blinded to each participant's assigned study intervention until all participants complete treatment.
Intervention model description
This is a Phase 2/ Phase 3, superiority, adaptive, two parallel-arm, randomized, multi-center, placebo-controlled, double-blind study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants aged 18 years or older at screening. * Diagnosis of RSV infection collected within 5 days prior to randomization. * New onset or worsening (if present chronically) of at least one of the following signs and/or symptoms consistent with a viral acute respiratory infection (ARI), within 5 days prior to randomization: nasal congestion, nasal discharge, sore throat, cough, sputum production, shortness of breath, or wheezing. * Has at least 1 of the following characteristics or underlying medical conditions: a) 65 years of age or older b) Chronic lung disease, c) Heart failure, d) Immunosuppressive disease/condition or immune-weakening medications
Exclusion criteria
* Any medical or psychiatric condition that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study or interfere with the evaluation of response to the study intervention. * Diagnosis of viral respiratory infections other than RSV including influenza and SARS-CoV-2 * Current need for hospitalization or anticipated need for hospitalization for any reason to provide inpatient/acute care within 24 hours after randomization * Any clinically significant ECG abnormality in the pre-dose ECG that, per investigator judgement, may affect participant safety * Has hypersensitivity to or other contraindication to any of the components of the study interventions, as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Respiratory Syncytial Virus (RSV) Related Hospitalization or Death From Any Cause Through Day 28 | From Day 1 (start of study intervention) up to Day 28 | RSV related hospitalization included a specialized acute medical care unit within an assisted living facility or nursing home. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression of Lower Respiratory Tract Infection (LRTI) Through Day 10 | From randomization on Day 1 up to Day 10 | Progression of LRTI was defined as development of LRTI or transition from non-severe LRTI-RSV at randomization to severe LRTI-RSV at any time up to and including Day 10. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 less than (\<) 95 percent (%) or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation. |
| Number of Participants With Development of LRTI Through Day 10 | From randomization on Day 1 up to Day 10 | Development of LRTI was defined as transitioning from not having LRTI at randomization but having nsLRTI-RSV or sLRTI-RSV at any time up to and including Day 10. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation. |
| Number of Participants With Resolution of LRTI at Day 15 | Day 15 | Resolution of LRTI was defined as transition from RSV-related non-severe LRTI (nsLRTI-RSV) or RSV-related severe LRTI (sLRTI-RSV) at randomization to not having nsLRTI and sLRTI-RSV. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation. |
| Mean Number of Hospital Free Days Through Day 28 | From Day 1 (start of study intervention) up to Day 28 | — |
| Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | From randomization on Day 1 up to Days 3, 5, 15 and 28 | Progression of LRTI was defined as development of LRTI or transition from non severe LRTI-RSV at randomization to severe LRTI-RSV at any time up to and including Days 3, 5, 15 and 28. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation. |
| Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | From randomization on Day 1 up to Days 3, 5, 15 and 28 | Development of LRTI was defined as transitioning from not having LRTI at randomization but having nsLRTI-RSV or sLRTI-RSV at any time up to and including Days 3, 5, 15 and 28. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation. |
| Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | At Days 3, 5, 10 and 28 | Resolution of LRTI was defined as transition from nsLRTI-RSV or sLRTI-RSV at randomization to not having nsLRTI and sLRTI-RSV. LRTI was defined as \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95% or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation. |
| Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | At Days 3, 5, 10, 15 and 28 | Improvement in LRTI status was defined as LRTI resolution or transition from sLRTI-RSV at randomization to nsLRTI-RSV. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation. |
| Number of Participants With RSV-Related Visits (Urgent Care/ Emergency Department (ED)/Hospital) or Death From Any Cause Through Day 28 | From Day 1 (start of study intervention) up to Day 28 | Participants with RSV related visits in a hospital/urgent care or ED requiring no minimum duration of hospitalization were reported in this outcome measure. Investigators determined if a medical visit was related to RSV. RSV-related medical visits were those attendances that would not otherwise occur in the absence of the RSV infection. These may have included: deterioration or decompensation of the lung function that required supplemental oxygen; development of secondary respiratory tract infections that required antibiotic treatment; management of severe symptoms associated with RSV such as fever; worsening or decompensation of cardiac or renal function in participants with underlying cardiac or renal disease. |
| Mean Number of RSV Related Days in Intensive Care Unit (ICU) Through Day 28 | From Day 1 (start of study intervention) up to Day 28 | — |
| Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | At Days 5, 10, 15, and 28 | Improvement was defined as no new acute respiratory infection (ARI) signs or symptoms, and no worsening of existing signs or symptoms compared to the Day 1 visit. At least one sign or symptom (but not all) present at Day 1 was absent, improved or returned to pre-infection status. Resolution was defined as all ARI signs or symptoms were absent or returned to pre-infection status. Clinical response was evaluated by the investigator. |
| Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | At Days 3, 5, 10, 15, and 28 | Undetectable RSV viral load at a visit was defined as a central PCR laboratory result of target not detected (TND). |
| Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Baseline (within 1 hour post start of study intervention on Day 1) and Days 3, 5, 10, 15, and 28 | Undetectable viral load was considered to be 0 copies/mL for this analysis. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through Day 35 | From Day 1 of study intervention up to 28-30 days after last dose of study drug (up to Day 35) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An adverse event was considered a TEAE if the event started on or after the study intervention start date (Day 1). |
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) Through Day 35 | From Day 1 of study intervention up to 28-30 days after last dose of study drug (up to Day 35) | An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria listed below: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic and other important medical event. |
| Plasma Concentrations of Sisunatovir at Days 3 and 5 | Anytime between 3 to 8 hours post dose on Day 3, and pre-dose on Day 5 | — |
| Mean Number of RSV Related Days in Hospital Through Day 28 | From Day 1 (start of study intervention) up to Day 28 | RSV related hospitalization included a specialized acute medical care unit within an assisted living facility or nursing home. |
Countries
China, India, Japan, United States
Participant flow
Recruitment details
A total of 16 participants were enrolled at 16 centers in the United States, China, Japan and India.
Participants by arm
| Arm | Count |
|---|---|
| Sisunatovir Participants received oral doses of sisunatovir from Day 1 to Day 5. | 8 |
| Placebo Participants received oral doses of placebo from Day 1 to Day 5. | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow up Phase | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Sisunatovir |
|---|---|---|---|
| Age, Continuous | 60.8 Years STANDARD_DEVIATION 9.13 | 62.3 Years STANDARD_DEVIATION 9.88 | 63.9 Years STANDARD_DEVIATION 10.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 12 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 4 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With Respiratory Syncytial Virus (RSV) Related Hospitalization or Death From Any Cause Through Day 28
RSV related hospitalization included a specialized acute medical care unit within an assisted living facility or nursing home.
Time frame: From Day 1 (start of study intervention) up to Day 28
Population: Modified Intent-to-Treat-Infected (mITT-infected) population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sisunatovir | Number of Participants With Respiratory Syncytial Virus (RSV) Related Hospitalization or Death From Any Cause Through Day 28 | 0 Participants |
| Placebo | Number of Participants With Respiratory Syncytial Virus (RSV) Related Hospitalization or Death From Any Cause Through Day 28 | 0 Participants |
Secondary
Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28
Undetectable viral load was considered to be 0 copies/mL for this analysis.
Time frame: Baseline (within 1 hour post start of study intervention on Day 1) and Days 3, 5, 10, 15, and 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sisunatovir | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 5 | -1.788 Log10 copies/mL | Standard Deviation 2.0327 |
| Sisunatovir | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 15 | -6.110 Log10 copies/mL | Standard Deviation 2.6486 |
| Sisunatovir | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 10 | -4.445 Log10 copies/mL | Standard Deviation 1.5779 |
| Sisunatovir | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 28 | -6.110 Log10 copies/mL | Standard Deviation 2.6486 |
| Sisunatovir | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 3 | -1.453 Log10 copies/mL | Standard Deviation 1.2107 |
| Placebo | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 28 | -4.900 Log10 copies/mL | Standard Deviation 1.7815 |
| Placebo | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 3 | -1.184 Log10 copies/mL | Standard Deviation 1.296 |
| Placebo | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 5 | -1.626 Log10 copies/mL | Standard Deviation 1.6493 |
| Placebo | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 10 | -2.784 Log10 copies/mL | Standard Deviation 1.8207 |
| Placebo | Change From Baseline in Log10 Transformed Total RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 15 | -4.900 Log10 copies/mL | Standard Deviation 1.7815 |
Secondary
Mean Number of Hospital Free Days Through Day 28
Time frame: From Day 1 (start of study intervention) up to Day 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sisunatovir | Mean Number of Hospital Free Days Through Day 28 | 28.0 Days | Standard Deviation 0 |
| Placebo | Mean Number of Hospital Free Days Through Day 28 | 28.0 Days | Standard Deviation 0 |
Secondary
Mean Number of RSV Related Days in Hospital Through Day 28
RSV related hospitalization included a specialized acute medical care unit within an assisted living facility or nursing home.
Time frame: From Day 1 (start of study intervention) up to Day 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sisunatovir | Mean Number of RSV Related Days in Hospital Through Day 28 | 0 Days | Standard Deviation 0 |
| Placebo | Mean Number of RSV Related Days in Hospital Through Day 28 | 0 Days | Standard Deviation 0 |
Secondary
Mean Number of RSV Related Days in Intensive Care Unit (ICU) Through Day 28
Time frame: From Day 1 (start of study intervention) up to Day 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sisunatovir | Mean Number of RSV Related Days in Intensive Care Unit (ICU) Through Day 28 | 0 Days | Standard Deviation 0 |
| Placebo | Mean Number of RSV Related Days in Intensive Care Unit (ICU) Through Day 28 | 0 Days | Standard Deviation 0 |
Secondary
Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28
Improvement was defined as no new acute respiratory infection (ARI) signs or symptoms, and no worsening of existing signs or symptoms compared to the Day 1 visit. At least one sign or symptom (but not all) present at Day 1 was absent, improved or returned to pre-infection status. Resolution was defined as all ARI signs or symptoms were absent or returned to pre-infection status. Clinical response was evaluated by the investigator.
Time frame: At Days 5, 10, 15, and 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sisunatovir | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 5 | 3 Participants |
| Sisunatovir | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 10 | 4 Participants |
| Sisunatovir | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 15 | 3 Participants |
| Sisunatovir | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 28 | 3 Participants |
| Placebo | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 28 | 5 Participants |
| Placebo | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 5 | 5 Participants |
| Placebo | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 15 | 5 Participants |
| Placebo | Number of Participants With a Clinical Response of Improvement or Resolution at Days 5, 10, 15, and 28 | Day 10 | 5 Participants |
Secondary
Number of Participants With Development of LRTI Through Day 10
Development of LRTI was defined as transitioning from not having LRTI at randomization but having nsLRTI-RSV or sLRTI-RSV at any time up to and including Day 10. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation.
Time frame: From randomization on Day 1 up to Day 10
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sisunatovir | Number of Participants With Development of LRTI Through Day 10 | 0 Participants |
| Placebo | Number of Participants With Development of LRTI Through Day 10 | 0 Participants |
Secondary
Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28
Development of LRTI was defined as transitioning from not having LRTI at randomization but having nsLRTI-RSV or sLRTI-RSV at any time up to and including Days 3, 5, 15 and 28. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation.
Time frame: From randomization on Day 1 up to Days 3, 5, 15 and 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sisunatovir | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 3 | 0 Participants |
| Sisunatovir | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 5 | 0 Participants |
| Sisunatovir | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 15 | 0 Participants |
| Sisunatovir | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 28 | 0 Participants |
| Placebo | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 28 | 0 Participants |
| Placebo | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 3 | 0 Participants |
| Placebo | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 15 | 0 Participants |
| Placebo | Number of Participants With Development of LRTI Through Days 3, 5, 15 and 28 | Day 5 | 0 Participants |
Secondary
Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28
Improvement in LRTI status was defined as LRTI resolution or transition from sLRTI-RSV at randomization to nsLRTI-RSV. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation.
Time frame: At Days 3, 5, 10, 15 and 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sisunatovir | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 5 | 1 Participants |
| Sisunatovir | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 15 | 1 Participants |
| Sisunatovir | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 10 | 1 Participants |
| Sisunatovir | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 28 | 2 Participants |
| Sisunatovir | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 3 | 1 Participants |
| Placebo | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 28 | 3 Participants |
| Placebo | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 3 | 2 Participants |
| Placebo | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 5 | 2 Participants |
| Placebo | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 10 | 2 Participants |
| Placebo | Number of Participants With Improvement of LRTI at Days 3, 5, 10, 15 and 28 | Day 15 | 3 Participants |
Secondary
Number of Participants With Progression of Lower Respiratory Tract Infection (LRTI) Through Day 10
Progression of LRTI was defined as development of LRTI or transition from non-severe LRTI-RSV at randomization to severe LRTI-RSV at any time up to and including Day 10. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 less than (\<) 95 percent (%) or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation.
Time frame: From randomization on Day 1 up to Day 10
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sisunatovir | Number of Participants With Progression of Lower Respiratory Tract Infection (LRTI) Through Day 10 | 0 Participants |
| Placebo | Number of Participants With Progression of Lower Respiratory Tract Infection (LRTI) Through Day 10 | 0 Participants |
Secondary
Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28
Progression of LRTI was defined as development of LRTI or transition from non severe LRTI-RSV at randomization to severe LRTI-RSV at any time up to and including Days 3, 5, 15 and 28. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation.
Time frame: From randomization on Day 1 up to Days 3, 5, 15 and 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sisunatovir | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 3 | 0 Participants |
| Sisunatovir | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 5 | 0 Participants |
| Sisunatovir | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 15 | 0 Participants |
| Sisunatovir | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 28 | 0 Participants |
| Placebo | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 28 | 0 Participants |
| Placebo | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 3 | 0 Participants |
| Placebo | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 15 | 0 Participants |
| Placebo | Number of Participants With Progression of LRTI Through Days 3, 5, 15 and 28 | Day 5 | 0 Participants |
Secondary
Number of Participants With Resolution of LRTI at Day 15
Resolution of LRTI was defined as transition from RSV-related non-severe LRTI (nsLRTI-RSV) or RSV-related severe LRTI (sLRTI-RSV) at randomization to not having nsLRTI and sLRTI-RSV. LRTI was defined as: \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95 % or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation.
Time frame: Day 15
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection. Here Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sisunatovir | Number of Participants With Resolution of LRTI at Day 15 | 1 Participants |
| Placebo | Number of Participants With Resolution of LRTI at Day 15 | 1 Participants |
Secondary
Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28
Resolution of LRTI was defined as transition from nsLRTI-RSV or sLRTI-RSV at randomization to not having nsLRTI and sLRTI-RSV. LRTI was defined as \>= 2 lower respiratory signs or symptoms for at least 24 hours including at least 1 lower respiratory sign; or 3 lower respiratory symptoms for at least 24 hours. Lower respiratory symptoms included following: new or increased sputum, new or increased cough, new or increased dyspnea (shortness of breath). Lower respiratory signs included: new or increased wheezing, new or increased crackles/ronchi based on chest auscultation, respiratory rate \>= 20 respirations/minute, low or decreased oxygen saturation (O2 \< 95% or \<= 90% if pre-season baseline is \< 95%), need for new or increased oxygen supplementation.
Time frame: At Days 3, 5, 10 and 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection. Here, Overall Number of Participants Analyzed signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sisunatovir | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 28 | 2 Participants |
| Sisunatovir | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 5 | 1 Participants |
| Sisunatovir | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 10 | 1 Participants |
| Sisunatovir | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 3 | 1 Participants |
| Placebo | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 28 | 3 Participants |
| Placebo | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 3 | 1 Participants |
| Placebo | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 10 | 1 Participants |
| Placebo | Number of Participants With Resolution of LRTI at Days 3, 5, 10 and 28 | Day 5 | 1 Participants |
Secondary
Number of Participants With RSV-Related Visits (Urgent Care/ Emergency Department (ED)/Hospital) or Death From Any Cause Through Day 28
Participants with RSV related visits in a hospital/urgent care or ED requiring no minimum duration of hospitalization were reported in this outcome measure. Investigators determined if a medical visit was related to RSV. RSV-related medical visits were those attendances that would not otherwise occur in the absence of the RSV infection. These may have included: deterioration or decompensation of the lung function that required supplemental oxygen; development of secondary respiratory tract infections that required antibiotic treatment; management of severe symptoms associated with RSV such as fever; worsening or decompensation of cardiac or renal function in participants with underlying cardiac or renal disease.
Time frame: From Day 1 (start of study intervention) up to Day 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sisunatovir | Number of Participants With RSV-Related Visits (Urgent Care/ Emergency Department (ED)/Hospital) or Death From Any Cause Through Day 28 | 0 Participants |
| Placebo | Number of Participants With RSV-Related Visits (Urgent Care/ Emergency Department (ED)/Hospital) or Death From Any Cause Through Day 28 | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through Day 35
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An adverse event was considered a TEAE if the event started on or after the study intervention start date (Day 1).
Time frame: From Day 1 of study intervention up to 28-30 days after last dose of study drug (up to Day 35)
Population: Safety analysis set (SAS) included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sisunatovir | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through Day 35 | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through Day 35 | 4 Participants |
Secondary
Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) Through Day 35
An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria listed below: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic and other important medical event.
Time frame: From Day 1 of study intervention up to 28-30 days after last dose of study drug (up to Day 35)
Population: SAS included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sisunatovir | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) Through Day 35 | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) Through Day 35 | 0 Participants |
Secondary
Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28
Undetectable RSV viral load at a visit was defined as a central PCR laboratory result of target not detected (TND).
Time frame: At Days 3, 5, 10, 15, and 28
Population: mITT-infected population included all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, and who had confirmed RSV infection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sisunatovir | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 5 | 0 Participants |
| Sisunatovir | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 15 | 4 Participants |
| Sisunatovir | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 10 | 1 Participants |
| Sisunatovir | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 28 | 4 Participants |
| Sisunatovir | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 3 | 0 Participants |
| Placebo | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 28 | 5 Participants |
| Placebo | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 3 | 0 Participants |
| Placebo | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 5 | 1 Participants |
| Placebo | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 10 | 2 Participants |
| Placebo | Number of Participants With Undetectable RSV Viral Load at Days 3, 5, 10, 15 and 28 | Day 15 | 5 Participants |
Secondary
Plasma Concentrations of Sisunatovir at Days 3 and 5
Time frame: Anytime between 3 to 8 hours post dose on Day 3, and pre-dose on Day 5
Population: Pharmacokinetic (PK) concentration analysis set included all participants who received at least 1 dose of sisunatovir and in whom at least 1 concentration value was reported. Here, Number Analyzed signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sisunatovir | Plasma Concentrations of Sisunatovir at Days 3 and 5 | Day 3 | 98.26 Nanogram per milliliter | Standard Deviation 141.41 |
| Sisunatovir | Plasma Concentrations of Sisunatovir at Days 3 and 5 | Day 5 | 173.1 Nanogram per milliliter | Standard Deviation 231.83 |