AGILE (Early Phase Platform Trial for COVID-19)

Master Protocol Inclusion Criteria: 1. Adults (≥18 years) with laboratory-confirmed\* SARS-CoV-2 infection (PCR) 2. Ability to provide informed consent signed by study patient or legally acceptable representative 3. Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use a highly effective method of contraception (as outlined in the protocol) from the first administration of trial treatment, throughout trial treatment and for the duration outlined in the candidate-specific trial protocol after the last dose of trial treatment * If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible. Standard additional criteria that may be applied per CST protocol: Group A (severe disease) 4a. Patients with clinical status of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, on non-invasive ventilation, or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (ventilation and additional organ support - pressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO)), as defined by the WHO clinical severity score, 9-point ordinal scale. Group B (mild-moderate disease) 4b. Ambulant or hospitalised patients with the following characteristics peripheral capillary oxygen saturation (SpO2) \>94% RA N.B. The CST protocol inclusion criteria will take precedence over the master protocol inclusion criteria. CST-2 Inclusion Criteria: For the purpose of the EIDD-2801 candidate-specific trial the following inclusion criteria have been amended from the Master protocol to: 1\. Male or female ≥ 60 years old or ≥50 years old with at least one well controlled comorbidity: cardiovascular disease, chronic lung disease (e.g. COPD, or pulmonary hypertension), immune deficiency (taking the equivalent of 20 mg prednisone daily, chemotherapy, or immune modulating biologic therapies), diabetes (treated with insulin or oral medications), BMI≥30, or hypertension requiring medication with laboratory confirmed SARS-CoV-2 infection (PCR) . 3\. Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use two effective methods of contraception, one of which should be highly effective (as outlined in the protocol). For women, from the first administration of trial treatment, throughout trial and up to 50 days after the last follow up visit (50 days after day 29) and for men with female partners of child bearing potential, from the first administration until 100 days after last follow up visit (100 days after day 29). 4\. Group B (mild-moderate disease): Ambulant with the following characteristics peripheral capillary oxygen saturation (SpO2) \>94% RA (NB this differs to the Master Protocol which also includes hospitalised patients in this group). Additional criteria specific to this candidate are: 5\. Has signs or symptoms of COVID-19 that began within 5 days of the planned first dose of study drug. 6\. Is in generally good health (except for current respiratory infection) and is free of uncontrolled chronic conditions. 7\. Is willing and able to comply with all study procedures and attending clinic visits through the 4th week. 8\. Has someone, aged ≥ 16 living in the same household during the dosing period. CST-6 Additional inclusion criteria: 1. Group A (severe disease). Patients with clinical status of Grades 5 (hospitalised, oxygen by mask or nasal prongs), 6 (hospitalised, on non-invasive ventilation, or high flow oxygen as defined by the WHO Clinical Progression Scale (WHO, 2020)). 2. Less than or equal to 14 days from onset of COVID-19 symptoms CST-8 Inclusion Criteria: 1. For the purpose of CST-8, criteria 1 has been amended from the Master Protocol to: Adults (≥18 years) outpatients positive lateral flow test at screening or baseline Day 1, who are within 5 days of symptom onset prior to the planned first dose of study drug. 2. Criteria 3 has been amended from the Master Protocol to: Women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP must agree to use a highly effective method of contraception (as outlined in section 5.5 of the Master Protocol) for the duration of the treatment and for six weeks following the last dose. Additional criteria specific to CST-8 are: * Initial onset of COVID-19 signs/symptoms within 5 days prior to the day of randomisation and at least 1 of the current specified COVID-19 signs/symptoms (listed on the NHS website) present on the day of randomisation * Is willing and able to comply with all study procedures and attending clinic visits CST-9a Inclusion Criteria: For the purpose of CST-9a, criteria 1 has been amended from the Master Protocol to: 1. Adults (\>/= 18 years of age) with a positive SARS-CoV-2 lateral flow test on screening or Day 1, who are at high risk (as defined in UK DHSC criteria) of progressing to severe COVID-19 disease, within 3 days of symptom onset, with at least one symptom of COVID-19 infection present on the day of randomization and are with mild- moderate disease severity at enrolment. Criterion 2 has been amended from the Master Protocol to: 2. Ability to provide informed consent signed by trial participant or legally acceptable representative and are willing and able to comply with all trial procedures and attending clinic visits Criterion 3 has been amended from the Master Protocol to: 3. Women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP must agree to use two effective methods of contraception, one of which must be highly effective for the duration of the treatment and for 90 Days following the last dose Master Protocol Exclusion Criteria: 1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>5 times the upper limit of normal (ULN) 2. Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) 3. Pregnant or breast feeding 4. Anticipated transfer to another hospital which is not a study site within 72 hours 5. Allergy to any study medication 6. Patients taking other prohibited drugs (as outline in CST protocol) within 30 days or 5 times the half-life (whichever is longer) of enrolment 7. Patients participating in another CTIMP trial N.B. The CST protocol exclusion criteria will take precedence over the master protocol exclusion criteria. CST-9a Exclusion Criteria: Exclusion criteria has been amended from master protocol as: 1. Prior SARS-CoV-2 infection \<90 days before enrolment and/or received any COVID-19 vaccine dose \<90 days before enrolment 2. Alanine aminotransferase (ALT) \>3 times the upper limit of normal (ULN) or Active Liver disease 3. History or current evidence of cirrhosis 4. Receiving dialysis or have known moderate to severe renal impairment (defined as CKD stage 4 or 5) or current acute kidney injury on most recent eGFR in the past 6 months 5. Pregnant or breast feeding 6. Anticipated transfer to another hospital which is not a trial site within 72 hours 7. Known allergy to any trial medication 8. Swallowing difficulties 9. Currently receiving ALG-097558, Paxlovid, molnupiravir or remdesivir or any SoC therapy for COVID-19 at the time of screening 10. Received sotrovimab at any point during the current SARS-CoV-2 infection 11. Oxygen saturations \<94% on room air 12. Urgent or expected need for nasal high-flow oxygen therapy or positive pressure ventilation, invasive mechanical ventilation or ECMO. 13. Participants who have taken or require treatment with a comedication that is a strong CYP450 3A4 inhibitor (atazanavir, clarithromycin, itraconazole, posaconazole, voriconazole, nefazodone, nelfinavir, grapefruit juice, HIV protease inhibitors), strong CYP450 3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) or sensitive substrates of CYP450 2C8 and 2B6 (repaglinide, rosiglitazone, paclitaxel, bupropion) within at least 2 weeks or 5 half-lives (whichever is longer) before the planned first dose of study drug. 14. Participating in another CTIMP trial CST-9b Exclusion criteria: 1. Prior SARS-CoV-2 infection diagnosed \<90 days before enrolment and/or received any COVID-19 vaccine dose \<90 days before enrolment 2. Alanine aminotransferase (ALT) \>3 times the upper limit of normal (ULN) or Active Liver disease 3. History or current evidence of cirrhosis 4. Receiving dialysis or have known severe renal impairment defined as CKD stage 5 (an eGFR \<15 mL/min/1.73 m2 at screening, or current acute kidney injury in most recent eGFR in past 6 months. 5. Pregnant or breast feeding 6. Anticipated transfer to another hospital which is not a trial site within 72 hours 7. Known allergy to any trial medication 8. Swallowing difficulties 9. Currently receiving ALG-097558, Paxlovid, molnupiravir or remdesivir or any standard of care antiviral therapy for COVID-19 at the time of screening 10. Received sotrovimab at any point during the current SARS-CoV-2 infection prior to enrolment 11. Oxygen saturations \<94% on room air. NOTE: Participants on stable oxygen therapy, including use of NIPPV (non-invasive positive pressure ventilation), for a pre-existing medical condition (e.g., COPD) may be included with oxygen saturation of \<94% on room air, provided there is no new increased oxygen requirement. 12. Urgent or expected need for nasal high-flow oxygen therapy or positive pressure ventilation, invasive mechanical ventilation or ECMO. 13. Participants who have taken or require treatment with a comedication that is a strong CYP450 3A4 inhibitor (atazanavir, clarithromycin, itraconazole, posaconazole, voriconazole, nefazodone, nelfinavir, grapefruit juice, HIV protease inhibitors), strong CYP450 3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) or sensitive substrates of CYP450 2C8 and 2B6 (repaglinide, rosiglitazone, paclitaxel, bupropion) within at least 2 weeks or 5 half-lives (whichever is longer) before the planned first dose of study drug. 14. Participating in another CTIMP trial within 5 half-lives of the last administered dose of an investigational medicinal product. 15. Participants eligible for other antiviral treatment according to DHSC criteria, or those otherwise eligible for CST9a.