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

Inclusion Criteria:

• Documentation of laboratory-confirmed active SARS-CoV-2 infection, as determined bya nucleic acid (for example, reverse-transcriptase PCR) or antigen test from anyrespiratory tract specimen (for example, oropharyngeal, NP or nasal swab, or saliva)collected ≤72 hours (3 days) prior to randomization.

• Participants are expected to begin study intervention ≤3 days from self-reporteddate of onset of any of the COVID-19-related symptoms from the following list:

• 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

• Nasal discharge

• Loss of taste

• Loss of smell

• One or more of the following signs/symptoms present within 24 hours prior torandomization:

• 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

• Nasal discharge

• Participants at higher risk of progression to severe COVID-19 are defined asfollows:

• Age ≥65 years

• Age ≥18 with 1 of the following:

• Obesity (body mass index [BMI] ≥30 kilograms per square meter [kg/m^2]). Note: BMIis rounded to the nearest whole number, for example 29.5 kg/m^2 is rounded to 30kg/m^2.

• Diabetes mellitus

• Hypertension requiring daily prescribed therapy

• Cardiovascular disease (requiring daily prescribed therapy or congenital heartdisease)

• Chronic lung disease (for example, chronic obstructive pulmonary disease, moderateto severe asthma, interstitial lung disease, cystic fibrosis, pulmonaryhypertension) requiring daily prescribed therapy

• Chronic kidney disease, defined as known current kidney impairment with a creatinineclearance (CrCl) or estimated glomerular filtration rate (eGFR) <60 milliliters (mL)/minute (min)/1.73 square meter (m^2) within the past 12 months prior torandomization, as long as the participant does not have known CrCl <30 mL/min byCockcroft-Gault or require dialysis

• Down syndrome

• Sickle cell disease

• One of the following immunocompromising conditions or immunosuppressive treatments:

• Receiving chemotherapy or other therapies for cancer

• Hematologic malignancy (active or in remission)

• History of a hematopoietic stem cell or a solid organ transplant

• Human immunodeficiency virus infection: not on antiretroviral therapy or withcluster of differentiation 4+ cell count <200 cells per cubic millimeter

• Combined primary immunodeficiency disorder

• Taking immunosuppressive medications (for example, drugs to suppress rejection oftransplanted organs or to treat rheumatologic and gastrointestinal conditions, suchas anti-tumor necrosis factor agents, mycophenolate, and rituximab).

Note: Current use of some corticosteroids is exclusionary, due to concern for possible drug-drug interaction (DDI) with S-217622.

Exclusion Criteria:

• History of hospitalization for the current SARS-CoV-2 infection (that is, priorhospitalization for a prior episode of SARS-CoV-2 infection is allowable)

• For the current SARS-CoV-2 infection, any positive SARS-CoV-2 molecular (nucleicacid) or antigen test from any respiratory tract specimen (for example,oropharyngeal, NP, or nasal swab, or saliva) collected ˃72 hours (3 days) prior torandomization. Participants with reinfection, defined as prior SARS-CoV-2 infectionthat began >90 days prior to the current onset of symptoms with interval resolutionof symptoms are eligible as long as the current infection has not been present formore than 3 days prior to randomization.

• Current need for hospitalization or immediate medical attention in the opinion ofthe investigator

• Current use of any medications prohibited with the study intervention. Individualswho have used Paxlovid or any other oral, inhaled, or injectable medication intendedto treat the current SARS-CoV-2 infection before randomization are excluded. Afterrandomization, locally available SARS-CoV-2 treatment (including but not limited tomolnupiravir, mAbs, outpatient IV remdesivir, convalescent plasma, inhaledbudesonide, favipiravir, and fluvoxamine) will be permitted, as long as there are noconcerns for DDIs.

Note: Paxlovid use for a prior episode of COVID-19 is permitted.

• Receipt of any investigational treatments for the current episode of SARS-CoV-2 atany time prior to randomization is exclusionary. Note: This does not include drugsapproved for other uses and taken for those indications or COVID-19 vaccines. Note:Use of locally authorized or approved therapies to prevent COVID-19, such as mAbsgiven solely to prevent COVID-19, are not exclusionary.

• Any co-morbidity requiring surgery within 7 days prior to randomization or that isconsidered life threatening in the opinion of the investigator within 28 days priorto randomization

• Known allergy/sensitivity or any hypersensitivity to components of S-217622 orplacebo for S-217622

• Known (within 12 months prior to randomization) renal impairment defined as CrCl <30mL/min by Cockcroft-Gault or requiring dialysis

• Known history of cirrhosis or liver decompensation (including ascites, varicealbleeding, or hepatic encephalopathy)

• Participants who have used any of the following drugs within 14 days prior torandomization:

• Strong cytochrome P453A inducer

• Products containing St. John's Wort