Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID (PREVAIL-LC)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Long COVID; Post-Acute COVID-19; Post Acute Sequelae of COVID-19
• Intervention / Treatment: Drug: Ensitrelvir; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Peluso, MD; Phone Number: (415) 476-4082 x119; Email: Michael.Peluso@ucsf.edu
• Study Contact Backup: Name: Emily Fehrman, MPH; Phone Number: (650) 761-2163; Email: Emily.Fehrman2@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • UCSF/Zuckerberg San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Change (PGIC)	The self-report measure Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of their treatment. We will use a modified PGIC scale which has been used to study pain syndromes and has been employed in other Long COVID clinical trials. It is a common data element developed by the National Institutes of Mental Health.	At 4 days and 10 days following administration
Distance walked on 6 minute walk test (6MWT).	This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on 6MWT performance between baseline and at 3 months post-administration. The 6MWT requires an individual to walk at their normal pace for 6 minutes on a marked track (for example, a hallway). Vital signs are assessed, and the total distance covered is the primary outcome of interest.	Baseline and 10 days following administration
Global health score on a 100-point visual-analogue scale	This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on self-reported score on a 100-point visual-analogue scale, where 0 represents the worst health a person can imagine and 100 represents the best health a person can imagine.	Baseline and 10 days following administration
CNS-Vital Signs Global Neurocognitive Index	This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on CNS-Vital Signs neurocognitive testing performance between baseline and at 60 days post-administration. CNS-VS is a computerized testing battery that participants will complete at baseline and follow-up visits. The global neurocognitive index is a summary score that comprises multiple domains.	Baseline and 10 days following administration

Collaborators and Investigators

• Sponsor: Timothy Henrich
• Collaborators: Shionogi Inc.
• Investigators: Principal Investigator: Timothy Henrich, MD, University of California, San Francisco; Principal Investigator: Michael Peluso, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Antiviral; Viral Persistence
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Chronic Disease; Post-Infectious Disorders; COVID-19; Inflammation; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: 23-38752

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No