Trial Outcomes & Findings for A Study to Compare S-217622 With Placebo in Non-Hospitalized Participants With COVID-19 (NCT NCT05305547)

A Study to Compare S-217622 With Placebo in Non-Hospitalized Participants With COVID-19

Time to sustained symptom resolution was defined as the time from start of study intervention to the first day of 2 consecutive days with complete resolution of COVID-19 symptoms on participant self-assessment and alive and without hospitalization for any reason by Day 29. Hospitalization was defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms, urgent care clinics, or facilities instituted to address medical needs of those with COVID-19.

NP swabs were collected by staff during in-person visits for measurement of SARS-CoV-2 RNA levels by quantitative log10 polymerase chain reaction (PCR). Results reported as log10 (RNA copies/milliliter \[mL\]).

Hospitalization was defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms, urgent care clinics, or facilities instituted to address medical needs of those with COVID-19. Hospitalization was adjudicated to be COVID-19-related. All deaths regardless of occurrence outside of hospital or during hospitalization (not adjudicated) are reported.

Time to sustained symptom resolution was defined as the time from start of study intervention to the first day of 2 consecutive days with complete resolution of COVID-19 symptoms on participant self-assessment and alive and without hospitalization for any reason by Day 29. Hospitalization was defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms, urgent care clinics, or facilities instituted to address medical needs of those with COVID-19. Wald confidence interval reported.

NP swabs were collected by staff during in-person visits for measurement of SARS-CoV-2 RNA levels by quantitative log10 PCR.

The number of participants with persistent and/or late-onset symptoms of COVID-19 at Week 12 based on participant assessment of the 5 symptoms specified by the World Health Organization (WHO) (fatigue, shortness of breath/difficulty breathing, difficulty with concentration/ thinking, difficulty reasoning/solving problems, and memory loss) plus taste disturbance and smell disturbance.

The time to sustained symptom resolution was defined as the first day of 2 consecutive days with complete resolution of COVID-19 symptoms on participant self-assessment and being alive and without hospitalization for any reason by Day 29. Data are reported for time (days) from start of ensitrelvir or placebo (Day 1) until sustained resolution based on assessments for 2 consecutive days of 6 targeted symptoms (nasal obstruction or congestion, nasal discharge, sore throat, cough, feeling feverish, and fatigue) and being alive and not hospitalized for any reason. Hospitalization was defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms, urgent care clinics, or facilities instituted to address medical needs of those with COVID-19.

The time to sustained symptom resolution was defined as the first day of 2 consecutive days with complete resolution of COVID-19 symptoms on participant self-assessment and being alive and without hospitalization for any reason by Day 29. Time (days) from start of ensitrelvir or placebo (Day 1) until sustained resolution (where cough and fatigue were considered resolved if they remain mild) based on assessments for 2 consecutive days of all targeted symptoms excluding loss of taste and loss of smell (cough, shortness of breath or difficulty breathing, feeling feverish, chills, fatigue, body pain or muscle pain or aches, diarrhea, nausea, vomiting, headache, sore throat, nasal obstruction or congestion, and nasal discharge) and being alive and not hospitalized for any reason by Day 29. Hospitalization was ≥24 hours of acute care, in a hospital or similar acute care facility (emergency rooms, urgent care clinics, or facilities instituted to address medical needs of those with COVID-19).

NP swabs were collected by staff during in-person visits for measurement of SARS-CoV-2 RNA levels by viral titer by culture.

Hospitalization was defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms, urgent care clinics, or facilities instituted to address medical needs. All deaths regardless of occurrence outside of hospital or during hospitalization (not adjudicated) are reported.

NP swabs were collected by staff during in-person visits for measurement of SARS-CoV-2 RNA levels by log10 quantitative PCR.

NP swabs were collected by staff during in-person visits per protocol for measurement of log10 SARS-CoV-2 RNA levels by quantitative PCR.

Participants kept a log of symptoms and major events in their study diary. The time to self-reported return to health (in days) was derived as: (the date of self-reported return to usual \[pre-COVID-19 health\] - (the date of first dose of study intervention) + 1.

The severity of COVID-19 disease was assessed using the WHO ordinal scale. The scale ranged from 1 to 8 and focuses primarily on the participant's oxygen need when they first came to the hospital. Scores include: 1 = no limitation of activities; 2 = limitation of activities; 3 = hospitalized no oxygen therapy; 4 = oxygen by mask or nasal prongs; 5 = non-invasive ventilation or high flow oxygen; 6 = intubation and mechanical ventilation; 7 = ventilation and additional organ support, pressors, renal replacement therapy, extra corporeal membrane oxygenation; 8 = death. Higher scores indicated greater severity of illness and a need for more intensive medical support.

Resting peripheral oxygen saturation was measured as the percentage of oxygen transported throughout the participant's body. An increase in percentage indicated an increased oxygen supply throughout the body.

Resting peripheral oxygen saturation was measured as the percentage of oxygen transported throughout the participant's body. Saturation levels at ≥96% indicated effective oxygen transportation throughout the body. A decrease in percentage indicated decreased oxygen supply throughout the body.

A participant was considered to have persistent and/or late-onset symptoms if either 1 of the following criteria was met: occurrence of at least 1 of the following symptoms at Week 24: difficulty with concentration/thinking, difficulty reasoning/solving problems, or memory loss; or occurrence of at least 1 of the following symptoms at Week 24: fatigue, shortness of breath/difficulty breathing, taste disturbance, or smell disturbance. Symptom severity assessed as: None; Mild; Moderate; Severe; At least Mild.

NP swabs were collected by staff during in-person visits for measurement of SARS-CoV-2 RNA levels by log10 quantitative PCR. Symptomatic viral rebound was defined as an increase in NP SARS-CoV-2 RNA levels by quantitative PCR or an increase in NP SARS-CoV-2 viral culture.

NP swabs were collected by staff during in-person visits for measurement of SARS-CoV-2 RNA levels by quantitative PCR. Viral rebound was defined as an increase in quantitative NP SARS-CoV-2 viral culture or NP SARS CoV-2 RNA levels by quantitative PCR.

The SF-36v2 is a 36-item, participant-reported survey of participant health that measures 8 scales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Each component was directly transformed into a 0 to 100 scale on the assumption that each question carried equal weight. A score of 0 was equal to maximum disability, and a score of 100 indicated no disability. Mean change could range from -100 to 100. A positive mean change indicated an improved outcome.

The EQ-5D-5L VAS is an instrument for self-reported assessment that ranks participant health status. Participants self-rate their health status using a scale of best health imaginable (100) to worst health imaginable (0). An increase in score indicates an improved health status.

Participants completed a post-acute COVID-19 questionnaire at each scheduled visit. The questionnaire is a survey instrument used to help measure functional health and health-related quality of life post-acute COVID-19. One of the items the questionnaire captures was whether the participant sought urgent medical care at an emergency room or clinic for specified symptoms (answered 'Yes' or 'No'). Symptoms ranged from cough and shortness of breath or difficult breathing to difficulty reasoning and solving problems and memory loss (short or long term). The number of participants answering 'Yes' to this question is reported.

All participants in the mITT set who experienced death due to any cause are reported. All deaths regardless of occurrence outside of hospital or during hospitalization (not adjudicated) are reported.

Plasma samples were collected at specified timepoints to measure ensitrelvir levels. Results reported as micrograms/milliliter (ug/mL).