Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID

Placebo-Controlled, Randomized Trial of Ensitrelvir (S-217622) for Viral Persistence and Inflammation in People Experiencing Long COVID (PREVAIL-LC)

Persistent viral infection with viral reservoirs and detection of circulating spike protein after the initial acute illness is one potential pathogenic mechanism for Long COVID. This mechanism may be susceptible to antiviral therapy that blocks viral replication, which has the potential to alleviate long COVID symptoms. This trial will study the safety and efficacy of Ensitrelvir (S-217622), an antiviral, to treat individuals with Long COVID in an adult population.

The study will enroll approximately 40 participants who meet the World Health Organization (WHO) Long COVID criteria. Participants will be enrolled at a single center and randomized 1:1 to receive ensitrelvir fumaric acid (Ensitrelvir: S-217622), given orally for 5 days, or placebo. Subjects randomized to receive Ensitrelvir will take 375 mg on day 1, followed by 125 mg daily for 4 additional days. Evaluations will take place at baseline and at timepoints up to 60 days post-initiation of study drug.

Inclusion Criteria (note, additional eligibility criteria not listed here will be assessed at Screening):

• ≥18 and <70 years of age at Screening.
• History of confirmed SARS-CoV-2 infection.
• Long COVID attributed to a SARS-CoV-2 infection
• At least two moderate symptoms or one severe symptom that are new or worsened since the time of a SARS-CoV-2 infection, not known to be attributable to another cause upon assessment by the PI. Symptoms must have been present for at least 60 days prior to screening and must be reported to be at least somewhat bothersome.
• Body mass index (BMI) 18 to 50 kilograms/meter squared (kg/m2), inclusive, at the time of screening.
• Participants who are of childbearing potential (CBP) and male participants with sexual partner(s) who are females of CBP must agree to use adequate contraception from study consent through 14 days after the last dose of study intervention.

Exclusion Criteria (note, additional eligibility criteria not listed here will be assessed at Screening):

• Previously received SARS-CoV-2 antiviral within 90 days prior to planned Day 0 or plan to receive such treatment before exiting the study
• Previously received COVID-19 convalescent plasma treatment within 60 days prior to planned Day 0 or plan to receive such treatment before exiting the study.
• Plans to receive any investigational or approved vaccine or booster for SARS-CoV-2 within 60 days prior to Day 0 or before Day 30 following Day 0.
• Active cardiovascular disease or recent (within 3 months) stroke.
• Recent (within 6 months) or planned major surgery.
• Currently hospitalized or recent (within 1 month) unplanned hospitalization.
• Active Hepatitis B or C infection.
• Known HIV infection.
• Severe coagulopathy (international normalized ratio ((INR) >2.0, history of hemophilia).
• Severe anemia (hemoglobin <9 grams/deciliter (g/dL)).
• Moderate or severe immunocompromise, according to the current NIH COVID-19 Treatment Guidelines as of March 6, 2023.
• History of anaphylaxis or hypersensitivity to any components of the intervention, prescription or non-prescription drugs, or food products in the past.
• Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), preceding and not related to SARS-CoV-2 infection and not worsened since SARS-CoV-2 infection
• Pregnant, breastfeeding, or unwilling to practice birth control abide by the contraception requirements outlined in the inclusion criteria.
• Participation in a clinical trial with receipt of an investigational product within 28 days prior to Day 0.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.