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)
Overview
- Phase
- Phase 3
- Intervention
- STI-1558
- Conditions
- COVID-19
- Sponsor
- Zhejiang ACEA Pharmaceutical Co. Ltd.
- Enrollment
- 1218
- Locations
- 2
- Primary Endpoint
- Time from the first dose to sustained recovery from 11 target symptoms of COVID-19.
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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;
Arms & Interventions
Arm A
* STI-1558 * n=600
Intervention: STI-1558
Arm B
* Placebo * n=600
Intervention: STI-1558 placebo
Outcomes
Primary Outcomes
Time from the first dose to sustained recovery from 11 target symptoms of COVID-19.
Time Frame: Time from the first dose to the day when the score of each of the 11 target symptoms of COVID-19 is 0.
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.
Secondary Outcomes
- Time from the first dose to sustained recovery from 5 designated symptoms of COVID-19.(Time from the first dose to the day when the score of each of the 5 designated symptoms of COVID-19 is 0.)
- 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.(From the first dose to Day29/Day14.)
- 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 Day4 and Day6.(From the first dose to Day4 and Day6.)
- Proportion of subjects with negative SARS-CoV-2 RNA conversion at each visit from the first dose to Day14.(From the first dose to Day14.)
- Area under the SARS-CoV-2 RNA load-time curve (AUC) between the first dose and Day6.(From the first dose to Day6.)
- 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.(From the first dose to Day29.)
- 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.(From the first dose to the day when the score of each of the COVID-19 symptoms is 0 or 1.)
- 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.(From the signing of informed consent to the 29 th day of administration.)