What is the mechanism of action of this treatment?

Protease inhibitors, such as ensitrelvir, target the 3C-like protease enzyme of the SARS-CoV-2 virus, which is crucial for viral replication. By inhibiting this enzyme, these drugs prevent the virus from processing its polyproteins, thereby halting its ability to replicate and spread within the host. This mechanism is vital for COVID-19 patients as it directly reduces viral load, potentially leading to milder symptoms, shorter illness duration, and decreased transmission risk. Effective antiviral treatments can significantly improve patient outcomes and help manage the spread of the virus.

What side effects are associated with this type of intervention?

Common treatments for COVID-19, including direct-acting antivirals like remdesivir, can cause side effects such as nausea, elevated liver enzymes, and potential allergic reactions. Corticosteroids like dexamethasone may lead to hyperglycemia, increased risk of infections, and gastrointestinal bleeding. Investigational agents such as fluvoxamine have been associated with gastrointestinal symptoms and potential drug interactions, while ivermectin misuse can result in severe toxicity, including neurologic adverse effects. It is important to use these treatments under medical supervision to manage and mitigate side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for COVID-19, including direct-acting antiviral agents. One notable example is remdesivir, which inhibits the viral RNA-dependent RNA polymerase. While not a 3C-like protease inhibitor, remdesivir is a key antiviral used in the treatment of COVID-19. Monoclonal antibodies, such as casirivimab and imdevimab, have also been authorized for emergency use, although their efficacy varies with different SARS-CoV-2 variants. As of now, no 3C-like protease inhibitors have received FDA approval specifically for COVID-19 treatment, making the ongoing trials of S-217622 (ensitrelvir) particularly significant.

What other types of research exist?

Promising alternatives to S-217622 (ensitrelvir) for COVID-19 treatment include: 1) Remdesivir, which is effective in reducing hospitalization risk in nonhospitalized patients and is suitable for children and adults. 2) Nirmatrelvir-ritonavir, which has shown efficacy in preventing severe outcomes in nonhospitalized patients but requires careful management of drug interactions. 3) Molnupiravir, available under EUA for high-risk adults, though it is not suitable for pregnant individuals. These alternatives offer different administration routes and target populations, providing flexibility in treatment options.

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Shionogi Protease Inhibitor for COVID-19

Phase 3

Recruiting

Led By Jens Lundgren, PhD

Research Sponsored by University of Minnesota

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥18 years

Hospitalized for the management of COVID-19, with signs and/or symptoms suggestive of lower respiratory tract infection

Must not have

Moribund condition, defined as prior cardiac arrest during this hospitalization and life expectancy less than 48 hours of randomization

Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 60 days post-treatment

Awards & highlights

Pivotal Trial

Summary

This trial will test a new medicine called ensitrelvir to help hospitalized COVID-19 patients by stopping the virus from multiplying.

Who is the study for?

Adults hospitalized for COVID-19 with symptoms of a lower respiratory tract infection can join this trial. They must have tested positive for SARS-CoV2 within the last 14 days and shown symptoms in the past two weeks. Excluded are those with severe health conditions, certain drug interactions, or women who could get pregnant but won't use contraception.

What is being tested?

The STRIVE trial is testing Shionogi's Protease Inhibitor (S-217622) against a placebo to see if it helps hospitalized COVID-19 patients when added to standard treatments like remdesivir. It's randomized and controlled, meaning some people will get the real drug and others a dummy pill without knowing which one they're taking.

What are the potential side effects?

Potential side effects aren't specified here, but protease inhibitors may commonly cause gastrointestinal issues like diarrhea, nausea; liver problems; rash; or metabolic changes such as increased blood sugar levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I am hospitalized for COVID-19 with symptoms affecting my lungs.

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I was admitted to the hospital with signs of a respiratory infection.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a cardiac arrest during this hospital stay and my doctors think I have less than 48 hours to live.

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My treatment is focused on comfort and managing symptoms, not on extending life.

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I am on long-term dialysis or kidney replacement therapy.

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I agree to use contraception or abstain from sex for 30 days after the last dose.

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My liver is not working well (moderate to severe issues).

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I do not have a life-threatening condition expected to cause death within a week, aside from my respiratory infection.

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I cannot take pills by mouth.

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I am not taking any medication that interacts badly with S-217622.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 60 days post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~60 days post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and 60 days post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Days to Recovery Scale assessed over 60 days (DRS-60)

Secondary study objectives

a 3-category ordinal outcome

mortality

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: S-217622 (ensitrelvir) plus standard of care (SOC)Experimental Treatment1 Intervention

Study investigational agent (ensitrelvir) will be administered as oral tablets with dosing of 375mg (3 tabs) once on Day 0 and 125mg (1 tab) once daily on Days 1-4. All participants will receive the full 5-day course, including those who are discharged from hospitalization prior to Day 4.

Group II: placebo plus standard of care (SOC)Placebo Group1 Intervention

Study investigational placebo will be administered as oral tablets with dosing of 375mg (3 tabs) once on Day 0 and 125mg (1 tab) once daily on Days 1-4. All participants will receive the full 5-day course, including those who are discharged from hospitalization prior to Day 4.

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Protease inhibitors, such as ensitrelvir, target the 3C-like protease enzyme of the SARS-CoV-2 virus, which is crucial for viral replication. By inhibiting this enzyme, these drugs prevent the virus from processing its polyproteins, thereby halting its ability to replicate and spread within the host. This mechanism is vital for COVID-19 patients as it directly reduces viral load, potentially leading to milder symptoms, shorter illness duration, and decreased transmission risk. Effective antiviral treatments can significantly improve patient outcomes and help manage the spread of the virus.