Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Long COVID, Post Acute Sequelae of COVID-19, Post-Acute COVID-19

Intervention / Treatment
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* Drug: Ensitrelvir
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ensitrelvir (S-217622)<br>Ensitrelvir fumaric acid (S-217622) given orally 375 mg on day 1 followed by 125 mg daily for 4 additional days | Drug: Ensitrelvir<br>* Those randomized to the experimental arm will receive Ensitrelvir, a protease inhibitor, taken orally for 5 days<br>* Other names: ensitrelvir fumaric acid;|
| Placebo Comparator: Placebo<br>Placebo administered orally for 5 days | Other: Placebo<br>* Matching placebo for Ensitrelvir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Score from Baseline. | This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on the PROMIS-29 scale between baseline and day 30. PROMIS-29 is a validated scale assessing physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, and pain. Each domain is scored on a 5-point scale (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do). | Baseline and 10 days following administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antiviral, Viral Persistence