A Phase 3 interventional study of Shionogi Protease Inhibitor (S-217622) and placebo in COVID-19, sponsored by University of Minnesota. Terminated at 187 sites in 24 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by University of Minnesota · Phase 3, Interventional, and Treatment
Treatments are needed to improve outcomes among patients hospitalized for COVID-19, including direct-acting antiviral (DAA) agents to mitigate the pathology driven by ongoing viral replication. This trial will evaluate S-217622 (ensitrelvir), an anti-SARS-CoV2 3C-like protease inhibitor (PI) developed by Shionogi \&; Co. Ltd.
The study design is a randomized, placebo-controlled, multi-center international clinical trial that will evaluate the clinical efficacy of ensitrelvir when given in addition to standard of care (SOC) for inpatients with COVID-19. The SOC will be determined by local established guidelines and may include additional DAA (e.g., remdesivir) and immunomodulatory treatment strategies. Certain SOC treatments will be pre-specified prior to randomization.
7,990 studies on the registry are indexed under COVID-19; 466 are open to participants now.
This study's enrollment of 602 is above the median of 102 across 4,364 interventional studies indexed under COVID-19.
Browse COVID-19 studies →University of Minnesota is the lead sponsor of 1,216 studies on the registry; 197 are open to participants now.
Of its 136 completed or terminated interventional studies of FDA-regulated products, 95 (70%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Shionogi Protease Inhibitor (S-217622)
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.
Drug: placebo
S-217622 (ensitrelvir) is an oral anti-SARS-CoV2 PI that does not require ritonavir co-administration The dose is 375/125 (375 mg on Day 0, followed by 125 mg daily on Days 1-4).
Also known as: ensitrelvir
Placebo is an oral tablet administered once (3 tabs) on Day 0 and once (1 tab) daily on days 1-4, 5-day course.
Number of Participants Recovered by Day 60
Number of participants who recovered by Day 60. Recovery was assessed through Day 60 using the Days to Recovery Scale.
Time frame: Through Day 60
Mortality
Percentage of participants who died through Day 60
Time frame: 60 days post-treatment
A 3-category Ordinal Outcome
A 3-category outcome that represents the participant's status on Day 60. The 3 categories are 1. Recovered on Day 60, 2. Alive, not recovered on Day 60, 3. Died by Day 60"
Time frame: 60 days post-treatment
Recovery
Number of participants that recovered, defined as returning to place of residence prior to the onset of COVD-19 illness for 14 consecutive days
Time frame: 60 days post-treatment
Percentage of Participants Who Died or Required New Invasive Mechanical Ventilation
Time frame: Through Day 60
| Milestone | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| Started | 293 | 296 |
| Completed | 282 | 284 |
| Not completed | 11 | 12 |
| Withdrew: Lost to follow-up | 7 | 9 |
| Withdrew: Withdrawal by subject | 4 | 3 |
Number of participants who recovered by Day 60. Recovery was assessed through Day 60 using the Days to Recovery Scale.
| Participants | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| Number of Participants Recovered by Day 60 | 250 | 252 |
Percentage of participants who died through Day 60
| Participants | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| Mortality | 18 | 13 |
A 3-category outcome that represents the participant's status on Day 60. The 3 categories are 1. Recovered on Day 60, 2. Alive, not recovered on Day 60, 3. Died by Day 60"
| Participants | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| Recovered | 250 | 252 |
| Alive, not recovered | 14 | 19 |
| Dead | 18 | 13 |
Number of participants that recovered, defined as returning to place of residence prior to the onset of COVD-19 illness for 14 consecutive days
| Participants | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| Recovery | 261 | 264 |
| Participants | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| Percentage of Participants Who Died or Required New Invasive Mechanical Ventilation | 19 | 15 |
Collected over From randomization through Day 60, up to 65 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | 18/293 (6.1%) | 25/293 (8.5%) | 52/293 (17.7%) |
| Placebo Plus Standard of Care (SOC) | 13/296 (4.4%) | 26/296 (8.8%) | 50/296 (16.9%) |
| Event | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| Cardiac failure congestiveCardiac disorders | 0/293 | 3/296 |
| AstheniaGeneral disorders | 2/293 | 0/296 |
| SyncopeNervous system disorders | 2/293 | 0/296 |
| COPDRespiratory, thoracic and mediastinal disorders | 2/293 | 2/296 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 2/293 | 0/296 |
| AnaemiaBlood and lymphatic system disorders | 1/293 | 0/296 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/293 | 0/296 |
| LeukocytosisBlood and lymphatic system disorders | 1/293 | 0/296 |
| PancytopeniaBlood and lymphatic system disorders | 1/293 | 0/296 |
| Vertigo positionalEar and labyrinth disorders | 1/293 | 0/296 |
| Event | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) |
|---|---|---|
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 9/293 | 11/296 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 5/293 | 2/296 |
| AstheniaGeneral disorders | 2/293 | 5/296 |
| HypertensionVascular disorders | 4/293 | 3/296 |
| NauseaGastrointestinal disorders | 1/293 | 4/296 |
| AnaemiaBlood and lymphatic system disorders | 3/293 | 1/296 |
| Abdominal painGastrointestinal disorders | 3/293 | 1/296 |
| FatigueGeneral disorders | 3/293 | 2/296 |
| Non-cardiac chest painGeneral disorders | 3/293 | 3/296 |
| COVID-19 pneumoniaInfections and infestations | 3/293 | 1/296 |
| Age, Continuous(years) | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) | Total |
|---|---|---|---|
| Mean | 66.8 ± 15.4 | 65.8 ± 17.1 | 66.3 ± 16.3 |
| Sex: Female, Male(Participants) | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) | Total |
|---|---|---|---|
| Female | 140 | 149 | 289 |
| Male | 153 | 147 | 300 |
| Race (NIH/OMB)(Participants) | S-217622 (Ensitrelvir) Plus Standard of Care (SOC) | Placebo Plus Standard of Care (SOC) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 1 | 2 |
| Asian | 51 | 48 | 99 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
| Black or African American | 29 | 29 | 58 |
| White | 175 | 183 | 358 |
| More than one race | 1 | 2 | 3 |
| Unknown or Not Reported | 35 | 33 | 68 |
Showing the first 100 of 187 sites across 24 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Dec 2022 to primary completion in Oct 2025, 34 months.
Results were first posted in Sep 2026, 10 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Ensitrelvir