Study to Assess the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Study Evaluating the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)

This is a multicenter, randomized, double-blind, placebo-controlled phase III clinical study to evaluate the efficacy and safety of STI-1558 in adult subjects with mild/moderate COVID-19. One thousand and two hundred adult subjects with mild/moderate COVID-19 (including subjects with high risk factors for progression into severe cases) are planned to be enrolled and randomized in a ratio of 1:1 into the test group or the placebo group (600 in the test group and 600 in the placebo group).

One thousand and two hundred adult subjects with mild/moderate COVID-19 (including subjects with high risk factors for progression into severe cases) are planned to be enrolled and randomized in a ratio of 1:1 into the test group or the placebo group. Randomization and stratification factors include clinical type (mild vs. moderate) of COVID-19, high risk factors for severe disease (with vs. without), history of SARS-CoV-2 vaccination or infection (yes vs. no). Subjects in the test group will receive STI-1558, and subjects in the placebo group will receive STI-1558 placebo. STI-1558 and STI-1558 placebo will be orally administered under fasting condition twice daily (BID) for 5 days (10 doses in total) at a dose of 600 mg and 0 mg, respectively; the two doses administered will be at a minimum interval of 8 hours (≥8 h). Efficacy and safety will be assessed until D29 after the first dose.

Inclusion Criteria:

1. Males or females aged ≥18 years;
2. Subjects comply with the diagnostic criteria for mild or moderate COVID-19 specified in the Protocol for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial Version 9) released by China's National Health Commission;
3. First presence of positive RT-PCR or rapid antigen assay for SARS-CoV-2 with nasopharyngeal or oropharyngeal swabs within 4 days prior to the first dose (≤4 days from the first dose);
4. First presence of at least 1 of 14 symptoms of COVID-19 within 3 days prior to the first dose (≤3 days/72 hours from the first dose) ;
5. Subjects with at least 2 of 11 target symptoms of COVID-19 within 24 hours prior to the first dose (≤24 hours from the first dose), including at least 1 designated symptom (Stuffy or runny nose, Sore throat or dry throat, Cough, Feeling hot or feverish, Shortness of breath or difficulty breathing), and score of at least 1 designated symptom ≥2 ;
6. Women of childbearing potential (WOCBP) (women of non-childbearing potential defined as women who have undergone hysterectomy or bilateral oophorectomy or bilateral salpingectomy or bilateral tubal ligation/closure, or who are infertile due to a congenital or acquired condition, or sexually mature women spontaneously menopausal for ≥ 12 months) must have a negative pregnancy test during the screening period;
7. Female subjects of childbearing potential or male subjects whose partners are of childbearing potential must agree to use a highly effective contraceptive method from screening to 30 days after the last dose;
8. Can understand and abide by the procedures and methods of this clinical trial.

Exclusion Criteria:

1. Known allergy to any ingredient of the study drug;
2. Subjects comply with the diagnostic criteria for severe or critical COVID-19 specified in the Protocol for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial Version 9) released by China's National Health Commission prior to the first dose;
3. Subjects urgently require or is expected to require nasal high-flow oxygen therapy or non-invasive positive pressure ventilation, invasive mechanical ventilation or ECMO prior to the first dose;
4. Subjects with abnormal liver function at screening: total bilirubin ≥ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × ULN;
5. Subjects with active or uncontrolled hepatopathy: including cirrhosis, Child-Pugh grade B or C, acute liver failure, etc.;
6. Subjects with concomitant severe renal insufficiency (estimated glomerular filtration rate [eGFR]<45 mL/min, calculated using the serum creatinine based Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation, refer to Appendix 6 for the calculation formula) or on continuous renal replacement therapy, hemodialysis or peritoneal dialysis;
7. Subjects with impaired immune system (including subjects who are on systemic or inhaled corticosteroids or other immunosuppressants, or subjects with cancer progression or recurrence, or with human immunodeficiency virus [HIV] infection);
8. Subjects with acute episodes of chronic respiratory diseases (including bronchial asthma, chronic obstructive pulmonary disease, etc.);
9. Subjects with a history of dysphagia or any gastrointestinal disorder that affects drug adsorption;
10. Subjects with suspected or confirmed acute systemic infections other than COVID-19 (e.g., concomitant influenza), which may interfere with the evaluation of responses to the study intervention;
11. Subjects who have underwent major surgery within 14 days prior to the first dose, or have not completely recovered from surgery or plan to undergo surgery during the study period;
12. Subjects with complications that are, in the opinion of the investigator, life-threatening within 30 days prior to the first dose;
13. Subjects have received anti-SARS-CoV-2 chemical drugs such as 3CL protease inhibitors or RNA dependent RNA polymerase (RdRp) inhibitors or angiotensin converting enzyme 2 (ACE-2) and transmembrane protease serine 2 (TMPRSS2) degrading agents within 14 days prior to the first dose;
14. Subjects have received COVID-19 patients' convalescent plasma or COVID-19 human immunoglobulin or interleukin-6 (IL-6) inhibitors or anti-SARS CoV-2 neutralizing antibodies within 30 days or 5 half-lives (whichever is longer) prior to the first dose;
15. Subjects have had any SARS-CoV-2 vaccination within 3 months prior to the first dose;
16. Subjects have received any potent inhibitor or inducer of cytochrome P450 (CYP) 3A4 within 28 days or 5 half-lives (whichever is shorter) prior to the first dose;
17. Subjects who are currently participating in an interventional clinical study of other investigational drugs or devices, including other studies on COVID-19;
18. Subjects have received any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose;
19. Subjects have previously participated in this study or other studies of STI-1558;
20. Pregnant or lactating women;
21. Subjects with active serious mental illness, medical disorder or other symptoms/conditions that, in the opinion of the investigator, may affect treatment, compliance or the ability to provide informed consent.