Clinical trial NCT06161688: Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID
Official title: Placebo-Controlled, Randomized Trial of Ensitrelvir (S-217622) for Viral Persistence and Inflammation in People Experiencing Long COVID (PREVAIL-LC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Long COVID
Post Acute Sequelae of COVID-19
Post-Acute COVID-19
Keywords: Antiviral
Viral Persistence
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Shionogi Inc.
First posted: 2023-12-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score from Baseline.
timeFrame: Baseline and Day 10
Secondary outcomes:
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score from Baseline.
timeFrame: Baseline and Day 30
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score from Baseline.
timeFrame: Baseline and Day 10
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score from Baseline.
timeFrame: Baseline and Day 30
measure: Change in Quality of Life (Global Health Score) on a 100-point Visual-Analogue Scale from Baseline
timeFrame: Baseline and Day 10
measure: Change in Quality of Life Score (5-Item EuroQol EQ-5D-5L) Index Value Score from Baseline.
timeFrame: Baseline and Day 10
measure: Change in Duke Activity Status Index (DASI) from Baseline
timeFrame: Baseline and Day 10
measure: Change in Orthostatic Intolerance Score from Baseline
timeFrame: Baseline and Day 10
measure: Change in World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0) questionnaire from Baseline
timeFrame: Baseline and Day 10
measure: Patient Global Impression of Change (PGIC) at D10
timeFrame: Day 10
measure: Change in Everyday Cognition Form instrument from Baseline
timeFrame: Baseline and Day 10
measure: Change in 6 Minute Walking Test (6MWT) from Baseline
timeFrame: Baseline and Day 10
measure: Change in Active Stand Test from Baseline
timeFrame: Baseline and Day 10
measure: Change in Neurocognition Index (NCI) score from the CNS-VS from Baseline
timeFrame: Baseline and Day 10
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF/Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Timothy Henrich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Michael Peluso, MD
role: PRINCIPAL_INVESTIGATOR
References: