AGILE master platform protocol - seamless Phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment
COVID-19 (SARS-CoV-2 infection)
Current interventions as of 13/01/2026: CST-2 [Completed]: Phase I – Patients randomised to EIDD-2801 or standard of care (SOC). EIDD-2801 administered orally, twice daily (BID) for 10 doses (5 or 6 days). The starting dose was established based on safety and pharmacokinetics from a healthy volunteer study, sample size variable depending on dose escalation decisions, and patients recruited in cohorts of 6 patients and randomised in a 2:1 ratio between EIDD-2801 and SOC using permuted block randomisation. Patients are followed up until Day 29. CST-2 [Completed]: Phase II - Patients randomised to EIDD-2801 and SOC or Placebo and SOC. EIDD-2801 or placebo administered orally, twice daily (BID) for 10 doses (5 or 6 days). The dose of EIDD-2801 will be determined by the recommended dose from Phase I. Patients randomised 1:1 between EIDD-2801 and placebo using permuted block randomisation stratified by site. Patients are followed up until Day 29. 180 patients to be recruited. CST-3 [Completed]: (A) Healthy volunteers recruited in cohorts of twelve patients per cohort (36 patients max), with patients taking 1500 mg twice daily (max dose of 3500 mg total daily dose) of nitazoxanide. This trial has now completed recruiting and will move to CST-3B (COVID-19 patients) which is taking part internationally. CST-5 [Completed]: Phase I – patients randomised to VIR-7932 or placebo in cohorts of 3 with 8 patients each (total of 24 patients). This is a randomised and blinded 3:1 with doses of up to 500mg VIR-7832 will be evaluated. The doses will be either 50 mg, 150 mg or 500 mg or placebo. Administration will be via intravenous infusion. CST-5 [Completed]: Phase II – an additional 125 patients planned to be randomised 2:2:1 to VIR-7832, VIR-7831 or placebo of dose levels of 500mg for VIR-7832 or VIR-7831 or placebo. Patients will be followed up until Day 169. CST-6 [Completed]: A Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the Phase II d
Current key inclusion criteria as of 13/01/2026: The CST protocol inclusion criteria will take precedence over the master protocol inclusion criteria. Patients are eligible to be included in the study only if all of the following criteria apply (as well as all criteria from the appropriate CST protocol): 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, as defined in section 5.5 below) and male patients who are sexually active with WOCBP must agree to use a highly effective method of contraception 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) 4.1. Patients with clinical status of Grades 5 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, on non-invasive ventilation, or high flow oxygen), 7 (hospitalised, intubation and mechanical ventilation, pO₂/FiO₂ ≥150 or SpO₂/FiO₂ ≥200), 8 (hospitalised mechanical ventilation pO₂/FiO₂ <150 (SpO₂/FiO₂ <200) or vasopressors) or 9 (hospitalised, mechanical ventilation pO₂/FiO₂ <150 and vasopressors, dialysis or ECMO), as defined by the WHO Clinical Progression Scale Group B (mild-moderate disease) 4.2. Ambulant or hospitalised patients with the following characteristics peripheral capillary oxygen saturation (SpO₂) >94% RA Previous key inclusion criteria: The CST protocol inclusion criteria will take precedence over the master protocol inclusion criteria. Patients are eligible to be included in the study only if all of the following criteria apply (as well as all cri
Patients are excluded from the study if any of the following criteria apply (as well as all criteria from the appropriate CST protocol): 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 m²) 3. Pregnant or breastfeeding 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. Additional criteria specific to Candidate Specific Trial (CST-2) as of 30/11/2020 are: * The master protocol stipulates ‘Exclusion Criteria 4’ as ‘anticipated transfer to another hospital which is not a study site within 72 hours’. This is not applicable to this protocol as patients are expected to be out-patients. 8. Has a febrile respiratory illness that includes pneumonia that result in hospitalisation, or requires hospitalisation, oxygenation, mechanical ventilation, or other supportive modalities. 9. Has a platelet count less than 50x109/L. 10. Is experiencing adverse events or laboratory abnormalities that are Grade 3 or above based on the CTCAE v5 grading. 11. Has clinically significant liver dysfunction or renal impairment. 12. Has history of hepatitis C infection or concurrent bacterial pneumonia. 13. Has received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 30 days prior to the first dose of study drug. 14. In the opinion of the investigator, has significant end-organ disease as a result of relevant comorbidities: chronic kidney disease, congestive heart failure, peripheral vascular disease inc