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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: STI-1558
* Drug: STI-1558 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged ≥18 years; 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; 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); 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) ; 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 ; 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; 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; Can understand and abide by the procedures and methods of this clinical trial. Exclusion Criteria: Known allergy to any ingredient of the study drug; 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; 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; 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; Subjects with active or uncontrolled hepatopathy: including cirrhosis, Child-Pugh grade B or C, acute liver failure, etc.; 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; 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); Subjects with acute episodes of chronic respiratory diseases (including bronchial asthma, chronic obstructive pulmonary disease, etc.); Subjects with a history of dysphagia or any gastrointestinal disorder that affects drug adsorption; 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; 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; Subjects with complications that are, in the opinion of the investigator, life-threatening within 30 days prior to the first dose; 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; 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; Subjects have had any SARS-CoV-2 vaccination within 3 months prior to the first dose; 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; Subjects who are currently participating in an interventional clinical study of other investigational drugs or devices, including other studies on COVID-19; Subjects have received any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose; Subjects have previously participated in this study or other studies of STI-1558; Pregnant or lactating women; 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>STI-1558 n=600 | Drug: STI-1558<br>* STI-1558 will be orally administered under fasting condition twice daily (BID) for 5 days (10 doses in total) at a dose of 600 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.<br>|
| Placebo Comparator: Arm B<br>Placebo n=600 | Drug: STI-1558 placebo<br>* STI-1558 placebo will be orally administered under fasting condition twice daily (BID) for 5 days (10 doses in total) at a dose of 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from the first dose to sustained recovery from 11 target symptoms of COVID-19. | Sustained recovery from 11 target symptoms of COVID-19: the score of each of the 11 target symptoms of COVID-19 in the subject is 0 for ≥2 days. | Time from the first dose to the day when the score of each of the 11 target symptoms of COVID-19 is 0. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the SARS-CoV-2 RNA load (reverse transcriptase polymerase chain reaction [RT-PCR] assay) at each visit point from the first dose to Day6. | Change from baseline in the SARS-CoV-2 RNA load at each visit point. | From the first dose to Day6. | 
| Time from the first dose to sustained recovery from 5 designated symptoms of COVID-19. | Sustained recovery from 5 designated symptoms of COVID-19: the score of each of the 5 designated symptoms of COVID-19 (fever or feeling hot, cough, nasal obstruction or rhinorrhoea, pain pharynx or dry throat, shortness of breath or dyspnea) in the subject is 0 for ≥2 days. | Time from the first dose to the day when the score of each of the 5 designated symptoms of COVID-19 is 0. | 
| Proportion of subjects with negative SARS-CoV-2 RNA conversion at each visit from the first dose to Day14. | Proportion of subjects with negative SARS-CoV-2 RNA conversion at each visit. | From the first dose to Day14. | 
| Area under the SARS-CoV-2 RNA load-time curve (AUC) between the first dose and Day6. | Area under the SARS-CoV-2 RNA load-time curve (AUC) . | From the first dose to Day6. | 
| 1.Time from the first dose to sustained remission of 11 target symptoms of COVID-19. 2.Time from the first dose to sustained remission of 5 designated symptoms of COVID-19. 3.Time from the first dose to sustained remission of 14 symptoms of COVID-19. | Sustained remission of the symptoms of COVID-19: the score of each of the symptoms of COVID-19 in the subject is 0 or 1 for ≥2 days; time from the first dose to sustained remission of the symptoms of COVID-19: time from the first dose to the day when the score of each of the symptoms of COVID-19 is 0 or 1. | From the first dose to the day when the score of each of the COVID-19 symptoms is 0 or 1. | 
| 1.Time to sustained recovery/sustained remission. 2.Proportion of subjects with sustained recovery/sustained remission. 3.Proportion of each of 11 target symptoms by severity. 4.Scores of 11 target symptoms -time AUC from the first dose to Day14. | Sustained recovery from 11 target symptoms of COVID-19: the score of each of the 11 target symptoms of COVID-19 in the subject is 0 for ≥2 days; time from the first dose to sustained recovery from 11 target symptoms of COVID-19: time from the first dose to the day when the score of each of the 11 target symptoms of COVID-19 is 0. Sustained remission of 11 target symptoms of COVID-19: the score of each of the 11 target symptoms of COVID-19 in the subject is 0 or 1 for ≥2 days; time from the first dose to sustained remission of 11 target symptoms of COVID-19: time from the first dose to the day when the score of each of the 11 target symptoms of COVID-19 is 0 or 1. | From the first dose to Day29/Day14. | 
| Proportion of subjects: 1.Progressing into severe COVID-19. 2.Undergoing COVID-19 associated hospitalization or all-cause deaths. 3.Requiring assisted oxygen inhalation/ mechanical ventilation/ECMO. 4.Admitted into the ICU. 5.Number of days in ICU. | Proportion of subjects progressing into severe COVID-19/undergoing COVID-19 associated hospitalization or all-cause deaths/requiring assisted oxygen inhalation/admitted into the intensive care unit (ICU) / requiring mechanical ventilation/extracorporeal membrane oxygenation. | From the first dose to Day29. | 
| During treatment: 1. Incidence of all adverse events (AEs) and serious adverse events (SAEs); 2. Any clinically significant abnormality in vital signs or physical examination; 3. Any clinically significant abnormality in laboratory tests, ECG, etc. | Incidence of all AEs and SAEs;Any clinically significant abnormality in vital signs or physical examination or laboratory tests, ECG, etc. | From the signing of informed consent to the 29 th day of administration. |