A Study of S-892216 in Participants With COVID-19

Phase 2 Study of S-892216 in Participants Infected With SARS-CoV-2

The primary objective of this study is to investigate the antiviral effect of S-892216 in participants with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: S-892216; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Multiple Locations, Japan
    • Japanese Site 10
  • Multiple Locations, Japan
    • Japanese Site 11
  • Multiple Locations, Japan
    • Japanese Site 12
  • Multiple Locations, Japan
    • Japanese Site 13
  • Multiple Locations, Japan
    • Japanese Site 14
  • Multiple Locations, Japan
    • Japanese Site 15
  • Multiple Locations, Japan
    • Japanese Site 16
  • Multiple Locations, Japan
    • Japanese Site 17
  • Multiple Locations, Japan
    • Japanese Site 18
  • Multiple Locations, Japan
    • Japanese Site 19
  • Multiple Locations, Japan
    • Japanese Site 1
  • Multiple Locations, Japan
    • Japanese Site 20
  • Multiple Locations, Japan
    • Japanese Site 21
  • Multiple Locations, Japan
    • Japanese Site 22
  • Multiple Locations, Japan
    • Japanese Site 23
  • Multiple Locations, Japan
    • Japanese Site 24
  • Multiple Locations, Japan
    • Japanese Site 25
  • Multiple Locations, Japan
    • Japanese Site 26
  • Multiple Locations, Japan
    • Japanese Site 27
  • Multiple Locations, Japan
    • Japanese Site 28
  • Multiple Locations, Japan
    • Japanese Site 29
  • Multiple Locations, Japan
    • Japanese Site 2
  • Multiple Locations, Japan
    • Japanese Site 30
  • Multiple Locations, Japan
    • Japanese Site 31
  • Multiple Locations, Japan
    • Japanese Site 32
  • Multiple Locations, Japan
    • Japanese Site 33
  • Multiple Locations, Japan
    • Japanese Site 34
  • Multiple Locations, Japan
    • Japanese Site 35
  • Multiple Locations, Japan
    • Japanese Site 36
  • Multiple Locations, Japan
    • Japanese Site 3
  • Multiple Locations, Japan
    • Japanese Site 4
  • Multiple Locations, Japan
    • Japanese Site 5
  • Multiple Locations, Japan
    • Japanese Site 6
  • Multiple Locations, Japan
    • Japanese Site 7
  • Multiple Locations, Japan
    • Japanese Site 8
  • Multiple Locations, Japan
    • Japanese Site 9
• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Healthstar Research
  • Florida
    • Coconut Creek, Florida, United States, 33073
      • Invictus Clinical Research Group LLC
    • Coral Gables, Florida, United States, 33134
      • Hope Clinical Trials
    • Immokalee, Florida, United States, 34142
      • Advanced Research for Health Improvement LLC
    • Miami, Florida, United States, 33133
      • CCM Clinical Research Group
    • Miami, Florida, United States, 33126
      • LCC Medical Research
    • Miami, Florida, United States, 33176
      • Entrust Clinical Research
    • Miami, Florida, United States, 33144
      • Continental Clinical Research
    • Miami, Florida, United States, 33135
      • Global Health Clinical Trials
    • Miami, Florida, United States, 33185
      • Kendall South Medical Center Inc
    • Miami Lakes, Florida, United States, 33014
      • Palm Springs Community Health Center
    • Miami Lakes, Florida, United States, 33016
      • Quality Research of South Florida
    • Miami Lakes, Florida, United States, 33144
      • Oceane7 Medical & Research Center, Inc.
    • Orlando, Florida, United States, 32807
      • Combined Research Orlando Phase I-IV LLC
    • St. Petersburg, Florida, United States, 33705
      • Global Clinical Professionals
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Balanced Life Health Care Solutions
  • Texas
    • Brownsville, Texas, United States, 78520
      • PanAmerican Clincal Research
    • Dallas, Texas, United States, 75209
      • Alina Clinical Trials LLC
    • Forney, Texas, United States, 75126
      • Care United Research, LLC
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Clinical Research Partners LLC
  • West Virginia
    • Kingwood, West Virginia, United States, 26537
      • Frontier Clinical Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must weigh ≥40 kilograms
• Must have at least 2 COVID-19 signs/symptoms of mild or higher severity, or at least 1 sign/symptom of moderate or higher severity, within the 72 hours prior to randomization, and the symptoms must still be present in the 24 hours prior to randomization
• Documentation of laboratory-confirmed active SARS-CoV-2 infection, as determined by a nucleic acid (for example, qRT-PCR) or antigen test from any respiratory tract specimen (for example, oropharyngeal, NP or nasal swab, or saliva), or any other SARS-CoV-2 test approved according to local regulations, collected ≤72 hours (3 days) prior to randomization
• Oxygen saturation (SpO2) of ≥92% on room air adjusted for altitude and obtained at rest by study staff within the 24 hours prior to randomization. For a potential participant who regularly receives chronic supplementary oxygen for an underlying lung condition, SpO2 measured while on standard home oxygen supplementation level must be ≥92%.
• Capable and willing to complete an electronic participant diary
• Contraceptive use by female participants should be consistent with local regulations regarding the use of contraceptive methods for those participating in clinical studies. Note: The investigational medication may lead to an increase or decrease of sex hormone levels; therefore, hormonal contraception must not be used alone and must be combined with a barrier method.
• A woman of childbearing potential must have a negative urine pregnancy test within the 24 hours before the first dose of investigational intervention
• Must be randomized ≤72 hours from onset of COVID-19 symptoms (defined as the time point when at least 1 of the COVID-19 symptoms occurs)
• Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period unless meeting hospitalization criteria or reaching Day 28, whichever is earliest

Key Exclusion Criteria:

• High risk of progression to severe COVID-19, as defined in the protocol
• Documented respiratory infection (for example, influenza, respiratory syncytial virus) other than COVID-19 within the 14 days prior to the screening visit
• Known current renal impairment defined as estimated glomerular filtration rate <60 milliliters/minute/1.73 meters squared or requiring dialysis
• Known history of cirrhosis or liver decompensation (including ascites, variceal bleeding, or hepatic encephalopathy)

• Known history of any of the following abnormalities in the following clinical laboratory tests (within the 6 months prior to the screening visit):

  • Total bilirubin ≥2 × upper limit of normal (ULN) (except for Gilbert's syndrome)
  • Aspartate aminotransferase or alanine aminotransferase ≥2 × ULN

• A QT interval corrected using Fridericia's formula at the screening visit:

  • For males: >450 milliseconds (msec)
  • For females: >470 msec
• History of hospitalization for the current SARS-CoV-2 infection or anticipated need for hospitalization within 24 hours after randomization
• History of cancer except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
• Women with a history of osteoporosis
• Received or expected to receive any dose of a SARS-CoV-2 vaccine within 14 days of randomization or during the study through day 28
• Received or expected to receive any other COVID-19-specific treatment, including outpatient remdesivir, Paxlovid, molnupiravir, monoclonal antibodies, ensitrelvir, and convalescent plasma for the current COVID-19 infection
• Exposed to an investigational drug within 30 days or 5 half-lives of the drug prior to the screening visit

Note: Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo.	Drug: Placebo; Placebo will be administered orally as a tablet.
Experimental: S-892216: Dose 1; Participants will receive S-892216.	Drug: S-892216; S-892216 will be administered orally as a tablet.; Drug: Placebo; Placebo will be administered orally as a tablet.
Experimental: S-892216: Dose 2; Participants will receive S-892216.	Drug: S-892216; S-892216 will be administered orally as a tablet.
Experimental: S-892216: Dose 3; Participants will receive S-892216.	Drug: S-892216; S-892216 will be administered orally as a tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in SARS-CoV-2 Viral RNA Level on Day 4 as Assessed by Quantitative Reverse-transcription Polymerase Chain Reaction (qRT-PCR) of Nasopharyngeal (NP) Swabs	Baseline through Day 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Sustained (2 Consecutive Days) Resolution of COVID-19 Symptoms	Baseline through Day 28
Time to First Resolution of COVID-19 Symptoms	Baseline through Day 28
Time to Return to Pre-COVID-19 Health	Baseline through Day 28
Time to the First Negative SARS CoV-2 Viral RNA qRT-PCR Result	Baseline through Day 28
Time to the First SARS CoV-2 Viral RNA Viral RNA Level Less Than the Lower Limit of Quantitation (LLOQ)	Baseline through Day 28
Number of Participants With a Positive SARS CoV-2 Viral RNA qRT-PCR Test	Baseline, Days 2, 4, 6, 10, 14, 21, and 28
Change From Baseline in SARS CoV-2 Viral RNA Level	Baseline, Days 2, 6, 10, 14, 21, and 28
Area Under the Curve of Change From Baseline in SARS-CoV-2 Viral RNA Level Through Day 4 and Day 6	Baseline through Day 4 and Day 6
Plasma Concentration of S-892216	Days 2, 6, and 10

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2025
• Primary Completion (Actual): September 22, 2025
• Study Completion (Actual): September 22, 2025

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 9, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 27, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Protease Inhibitor; Mpro; S-892216; Main Protease; Nonstructural Protein 5; nsp5
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: 2314T1621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No