At a glance
ClinicalIndex Comparison Record- ✓Adults aged ≥18 years with laboratory-confirmed SARS-CoV-2 infection (PCR)
- ✓Ability to provide informed consent signed by study patient or legally acceptable representative
- ✓Contraception requirements for WOCBP and sexually active males
- ✓CST-2: Age ≥60 years or ≥50 years with at least one well-controlled comorbidity
- ✕ALT and/or AST >5 times upper limit of normal (ULN)
- ✕Stage 4 severe chronic kidney disease or requiring dialysis (eGFR <30 mL/min/1.73 m²)
- ✕Pregnant or breast feeding
- ✕Anticipated transfer to another hospital not a study site within 72 hours
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 Treatment
In Brief
A Phase 1 clinical trial evaluating CST-2: EIDD-2801, CST-2: Placebo, and 11 other interventions for Covid19. Currently recruiting, targeting 600 participants across 7 sites in 2 countries.
Detailed Summary
The AGILE platform master protocol allows incorporation of a range of identified and yet-to-be-identified candidates as potential treatments for adults with COVID-19 into the trial. Candidates will be added into the trial via candidate-specific trial (CST) protocols of this master protocol as appendices. Having one master protocol ensures different candidates are evaluated in the same consistent manor and opening up new trials for new candidates is more efficient. Inclusion of new candidates will be based on pre-clinical data, evidence in the clinical setting and GMP capabilities.
Study Details
Timeline
Arms & Interventions
EIDD-2801 (also known as MK-4482, molnupiravir). Phase Ib: EIDD-2801 will be administered orally, twice daily (BID) for 10 doses (5 or 6 days). The starting dose will be established based on safety and pharmacokinetics from the EIDD-2801-1001-US/UK study, and dose escalations may occur as described in this CST.
Phase 1b only (standard of care)
Phase II placebo blinded controlled
Phase Ia Nitazoxanide will be administered orally, initially twice daily (BID) for 14 doses (7 days). The starting dose will be 1500mg BID based on existing dose information, but dose adaptations may occur
Phase I: Single doses of VIR-7832 will be administered by intravenous (IV) infusion. The starting dose will be 50 mg, and dose escalations of 150 and 500 mg are anticipated.
Phase II: 500 mg dose of VIR-7831 will be given by IV infusion.
Phase I: placebo blinded controlled
Phase II experimental arm.
Standard of care
IV Favipiravir twice daily for 7 days. Starting dose 600 mg twice daily. Dose escalation to 1200 mg twice daily, 1800 twice daily, 2400 twice daily.
Standard of care
EIDD-2801 (also known as MK-4482, molnupiravir). Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
Molnupiravir 800mg Twice a day (BD) in combination with Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days as starting dose, with a de-escalation protocol reducing in increments of molnupiravir to 600mg BD, then 400mg BD if required. The dose of Paxlovid® will be fixed for all cohorts.
Standard of care
Phase II: 500 mg dose of VIR-7832 will be given by IV infusion.
Phase II: placebo blinded controlled
Phase II: ALG-097558 600 mg twice a day orally for 5 days
Phase II: ALG-097558 600 mg twice a day orally for 5 days in combination with IV remdesivir for 3 days (200 mg day 1, 100 mg day 2 and 3)
Phase II : standard of care
twice daily dose for 5 days
Interventions
CST-2 Phase Ib: EIDD-2801 will be administered orally, twice daily (BID) for 10 doses (5 or 6 days). The starting dose will be established based on safety and pharmacokinetics from the EIDD-2801-1001-US/UK study, and dose escalations may occur as described in this CST. Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
CST-2 Phase II: Placebo will be administered orally, twice daily (BID) for 10 doses (5 or 6 days).
CST3A \& CST3B Phase I: Nitazoxanide will be administered orally, initially twice daily (BID) for 14 doses (7 days). The starting dose will be 1500mg BID based on existing dose information, but dose adaptations may occur. Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
CST-5: Phase I, Single doses of VIR-7832 will be administered by intravenous (IV) infusion over 1 hour. The starting dose will be 50 mg, and dose escalations of 150 and 500 mg are anticipated, with escalation guided by emerging safety data and decision by the SRC. Phase II: As per Phase I, with the dose determined by the recommended phase II dose.
CST-5 Phase II: A 500 mg dose of VIR-7831 will also be given by IV infusion over 1 hour.
CST-5 Phase 1, Phase II: Placebo given by intravenous infusion over 1 hour
CST-6: Multiple doses of IV Favipiravir will be administered by intravenous (IV) infusion over 1 hour. Dosing regimen will be every 12 hours for 7 days duration. The starting dose will be 600mg (BID), and dose escalations to 1200mg (BID), 1800mg (BID) and 2400mg (BID) are anticipated as well as a de-escalation dose of 300mg (BID) if necessary, with de-escalation and escalation guided by emerging safety data and decision by the Safety Review Committee (SRC).
Molnupiravir 800mg Twice a day (BD) for 5 days as starting dose, with a de-escalation protocol reducing in increments of molnupiravir to 600mg BD, then 400mg BD if required.
Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days. The dose of Paxlovid® will be fixed for all cohorts.
ALG-097558 600 mg Twice a day (BD) for 5 days
ALG-097558 600 mg Twice a day (BD) for 5 days Remdesivir will be administered once daily by intravenous infusion over 30 to 120 minutes. 200 mg will be given on day 1 and 100 mg on day 2 and day 3.
NHS standard of care as per COVID-19 treatment guidelines
twice daily (Q12H) oral dose of ALG-097558
twice daily (Q12H) oral dose