Ensitrelvir for Post-COVID Syndrome

(PREVAIL-LC Trial)

Overseen By PREVAIL-LC Study

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Timothy Henrich

Must not be taking: SARS-CoV-2 antivirals, Convalescent plasma

Disqualifiers: Cardiovascular disease, Stroke, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 61

Duration: 1 week

40 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received a SARS-CoV-2 antiviral or COVID-19 convalescent plasma treatment recently, and you should not plan to receive any investigational or approved SARS-CoV-2 vaccine or booster shortly before or during the trial.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have received a SARS-CoV-2 antiviral or COVID-19 convalescent plasma treatment recently, and you should not plan to receive any COVID-19 vaccines or boosters during certain periods of the study.

What data supports the idea that Ensitrelvir for Post-COVID Syndrome is an effective drug?

The available research shows that Ensitrelvir is effective against various strains of the virus that causes COVID-19, including the Omicron variant and other new strains. It has been shown to work well in laboratory tests against these virus strains, suggesting it could be a strong option for treating COVID-19. Additionally, Ensitrelvir has been compared to another COVID-19 drug, molnupiravir, and has shown better results in some tests. This suggests that Ensitrelvir might be a more effective choice for treating COVID-19 and its symptoms. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Ensitrelvir for treating post-COVID syndrome?

Ensitrelvir has shown promising results as an antiviral drug against various strains of the virus that causes COVID-19, including the Omicron variant. It works by inhibiting a key enzyme needed for the virus to replicate, suggesting it could be effective in treating post-COVID syndrome by targeting the virus's ability to persist in the body. ^{1 2 3 4 5}

Is Ensitrelvir safe for humans?

Ensitrelvir has been evaluated for safety in clinical trials for COVID-19, and these studies have assessed its safety in humans, although specific safety outcomes are not detailed in the provided abstracts. ^{1 2 4 5 6}

What safety data is available for Ensitrelvir (S-217622/Xocova)?

Ensitrelvir, also known as S-217622 or Xocova, has been evaluated for safety in several studies. A phase 2/3 study assessed its safety and efficacy in patients with mild-to-moderate COVID-19, including during the Omicron variant epidemic. The phase 2b part of this study specifically focused on safety and efficacy. These studies suggest that Ensitrelvir is a promising treatment option, but detailed safety data from these trials would provide more specific insights into its safety profile. ^{1 2 4 5 6}

Is the drug Ensitrelvir a promising treatment for Post-COVID Syndrome?

Ensitrelvir is a promising drug because it has shown strong antiviral activity against various strains of the coronavirus, including new variants. It works by targeting key enzymes that help the virus replicate, making it effective against many types of coronaviruses. It has also been approved for emergency use in Japan, indicating its potential as a treatment for COVID-19. ^{1 2 3 4 5}

How is the drug Ensitrelvir unique for treating post-COVID syndrome?

Ensitrelvir is unique because it is an oral drug that targets the main protease enzyme of coronaviruses, showing broad-spectrum antiviral activity against various strains, including new variants. It acts on multiple replication enzymes, making it potentially effective against a wide range of coronaviruses, unlike other treatments that may target only specific strains. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Timothy J Henrich, MD

Principal Investigator

University of California, San Francisco

Michael Peluso, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Adults aged 18-70 with a history of confirmed COVID-19, experiencing Long COVID symptoms for at least 60 days that are moderately to severely bothersome. Participants must not be known to have other causes for their symptoms and should have a BMI between 18 and 50 kg/m2. They must also agree to use contraception if they can bear children.

Inclusion Criteria

I have had a confirmed case of COVID-19.

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

I do not have an active Hepatitis B or C infection.

Participation in a clinical trial with receipt of an investigational product within 28 days prior to Day 0

Severe anemia (hemoglobin <9 grams/deciliter (g/dL)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ensitrelvir or placebo orally for 5 days

1 week

1 visit (in-person) at baseline

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Multiple visits up to 60 days post-initiation

Treatment Details

Interventions

• Ensitrelvir

Trial Overview The trial is testing Ensitrelvir, an antiviral drug, against a placebo to see if it's safe and effective in treating Long COVID by potentially blocking viral replication that could cause persistent symptoms.

Participant Groups

Group I: Ensitrelvir (S-217622) Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Placebo administered orally for 5 days

Ensitrelvir is already approved in Japan for the following indications:

Approved in Japan as Xocova for:

• COVID-19

Who Is Running the Clinical Trial?

Timothy Henrich

Lead Sponsor

Trials

1

Recruited

40+

Shionogi Inc.

Industry Sponsor

Trials

10

Recruited

760+

Findings from Research

A phase 3 study is being conducted to evaluate the efficacy and safety of ensitrelvir, a novel oral protease inhibitor, in treating mild-to-moderate COVID-19 in patients regardless of their vaccination status or risk factors.

Preliminary results from a phase 2b study indicated that ensitrelvir reduced the time to resolution of COVID-19 symptoms compared to placebo, suggesting it may be an effective treatment option for patients with mild-to-moderate disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part). Yotsuyanagi, H., Ohmagari, N., Doi, Y., et al.[2023]

In a phase 2b study involving 341 patients with mild-to-moderate COVID-19, ensitrelvir significantly reduced SARS-CoV-2 viral titers compared to placebo, indicating its antiviral efficacy.

While ensitrelvir did not show a significant difference in overall COVID-19 symptom scores compared to placebo, it did improve specific acute and respiratory symptoms, and most adverse events reported were mild, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study. Mukae, H., Yotsuyanagi, H., Ohmagari, N., et al.[2023]

S-217622 (Ensitrelvir) is an approved treatment for SARS-CoV-2 that works by inhibiting a key enzyme (3CLpro) necessary for the virus's replication, and its analog YY-278 shows similar antiviral activity against this enzyme and the virus itself.

YY-278 not only retains favorable pharmacokinetic properties, such as good bioavailability, but also demonstrates broad anti-coronaviral activity against multiple coronaviruses, suggesting its potential for treating COVID-19 and other related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of deuterated S-217622 (Ensitrelvir) with antiviral activity against coronaviruses including SARS-CoV-2. Yang, Y., Cao, L., Yan, M., et al.[2023]

Ensitrelvir (S-217622) is an effective antiviral treatment for COVID-19, demonstrating comparable activity against various SARS-CoV-2 variants, including the recently emerging omicron subvariants.

The drug effectively inhibits mutated forms of the SARS-CoV-2 3C-like protease (3CLpro), maintaining its efficacy against 11 major mutations identified globally, suggesting it could remain effective against future variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally. Kawashima, S., Matsui, Y., Adachi, T., et al.[2023]

The investigational antiviral S-217622 shows strong potential against various SARS-CoV-2 variants, including new strains, by effectively inhibiting key replication enzymes like the main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and exoribonuclease (ExoN) with very low effective concentrations (EC50 values of 0.17 and 0.27 μM).

S-217622's unique mechanism of action as a nucleoside analog allows it to target multiple coronavirus strains, suggesting its broad-spectrum efficacy and readiness for clinical evaluation as a treatment for COVID-19 and potentially other coronaviruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Investigational Anti-SARS-CoV-2 Agent Ensitrelvir "S-217622": A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species. Eltayb, WA., Abdalla, M., Rabie, AM.[2023]

Ensitrelvir, a small-molecule antiviral targeting the 3C-like protease of SARS-CoV-2, showed comparable antiviral activity to nirmatrelvir in vitro across multiple cell lines and effectively reduced virus levels in animal models.

In vivo, ensitrelvir demonstrated equal to or greater efficacy than nirmatrelvir at similar or slightly lower unbound-drug plasma concentrations, suggesting it could be a valuable treatment option for SARS-CoV-2 infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy comparison of 3CL protease inhibitors ensitrelvir and nirmatrelvir against SARS-CoV-2 in vitro and in vivo. Kuroda, T., Nobori, H., Fukao, K., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part). [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Synthesis of deuterated S-217622 (Ensitrelvir) with antiviral activity against coronaviruses including SARS-CoV-2. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Novel Investigational Anti-SARS-CoV-2 Agent Ensitrelvir "S-217622": A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy comparison of 3CL protease inhibitors ensitrelvir and nirmatrelvir against SARS-CoV-2 in vitro and in vivo. [2023]