COVID-19
Conditions
Keywords
S-892216, Mpro, Main Protease, Nonstructural Protein 5, nsp5, Protease Inhibitor
Brief summary
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.
Interventions
DRUGS-892216
S-892216 will be administered orally as a tablet.
DRUGPlacebo
Placebo will be administered orally as a tablet.
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Time to the First Negative SARS CoV-2 Viral RNA qRT-PCR Result | 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 |
| Plasma Concentration of S-892216 | Days 2, 6, and 10 |
| Time to Sustained (2 Consecutive Days) Resolution of COVID-19 Symptoms | Baseline through Day 28 |
Countries
Japan, United States
Outcome results
None listed