Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID

NCT06161688 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 23-38752
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19

Keywords

Antiviral; Viral Persistence

Outcome Measures

Primary Outcomes (1)

• Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score

  This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo in baseline adjusted mean PROMIS-29 Physical Health Summary Score at 10 post-\[ADD\]. 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). A T-score is calculated from each individual domain. A T score of 50 represents the mean for US general adult population, and 10 is the standard deviation. A lower T score indicates worse physical health.

  Day 10

Secondary Outcomes (13)

• Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score

  Day 30

• Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score

  Day 10

• Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score

  Day 30

• Quality of Life (Global Health Score) on a 100-point Visual-Analogue Scale

  Day 10

• Quality of Life Score (5-Item EuroQol EQ-5D-5L) Index Value Score

  Day 10

Study Arms (2)

Ensitrelvir (S-217622)

EXPERIMENTAL

Ensitrelvir fumaric acid (S-217622) given orally 375 mg on day 1 followed by 125 mg daily for 4 additional days

Drug: Ensitrelvir

Placebo

PLACEBO COMPARATOR

Placebo administered orally for 5 days

Other: Placebo

Interventions

Ensitrelvir DRUG

Those randomized to the experimental arm will receive Ensitrelvir, a protease inhibitor, taken orally for 5 days

Also known as: ensitrelvir fumaric acid

Ensitrelvir (S-217622)

Placebo OTHER

Matching placebo for Ensitrelvir

Placebo

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Timothy Henrich: lead
• Shionogi Inc.: collaborator

Study Sites (1)

UCSF/Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

ensitrelvir

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This is a small proof-of-concept study.

Results Point of Contact

• Title: Timothy Henrich
• Organization: University of California San Francisco

Timothy.Henrich@ucsf.edu

(415) 502-2449

Study Officials

• Timothy Henrich, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Michael Peluso, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 8, 2023
• Study Start: April 9, 2024
• Primary Completion: December 20, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 2, 2026
• Results First Posted: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)