Persistent viral infection with viral reservoirs and detection of circulating spikeprotein after the initial acute illness is one potential pathogenic mechanism for LongCOVID. This mechanism may be susceptible to antiviral therapy that blocks viralreplication, which has the potential to alleviate long COVID symptoms. This trial willstudy the safety and efficacy of Ensitrelvir (S-217622), an antiviral, to treatindividuals 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.
Drug: Ensitrelvir
Those randomized to the experimental arm will receive Ensitrelvir, a protease inhibitor,
taken orally for 5 days
Other Name: ensitrelvir fumaric acid
Other: Placebo
Matching placebo for Ensitrelvir
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.
UCSF/Zuckerberg San Francisco General Hospital
San Francisco, California, United States