Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID

Long COVID Clinical Trial

— PREVAIL-LC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06161688
• Other study ID #: 23-38752
• Status: Recruiting
• Phase: Phase 2
• Start date: April 9, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: University of California, San Francisco
• Contact: PREVAIL-LC Study
• Phone: (650) 761-2163
• Email: PREVAIL-LCStudy[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Inflammation
• Long COVID

Intervention

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

Other:
• Placebo
Matching placebo for Ensitrelvir

Locations

Country	Name	City	State
United States	UCSF/Zuckerberg San Francisco General Hospital	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Timothy Henrich	Shionogi Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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