AGILE (Early Phase Platform Trial for COVID-19)

Sponsor
University of Liverpool
Study ID
NCT04746183
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • CST-2: EIDD-2801 — DRUG
    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: Placebo — DRUG
    CST-2 Phase II: Placebo will be administered orally, twice daily (BID) for 10 doses (5 or 6 days).
  • Nitazoxanide — DRUG
    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.
  • VIR-7832 — DRUG
    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.
  • VIR-7831 — DRUG
    CST-5 Phase II: A 500 mg dose of VIR-7831 will also be given by IV infusion over 1 hour.
  • CST-5: Placebo — DRUG
    CST-5 Phase 1, Phase II: Placebo given by intravenous infusion over 1 hour
  • Favipiravir — DRUG
    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 — DRUG
    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 — DRUG
    Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days. The dose of Paxlovid® will be fixed for all cohorts.
  • ALG-097558 — DRUG
    ALG-097558 600 mg Twice a day (BD) for 5 days
  • ALG-097558 and Remdesivir — DRUG
    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 — DRUG
    NHS standard of care as per COVID-19 treatment guidelines
  • ALG-097558 — DRUG
    twice daily (Q12H) oral dose of ALG-097558
  • Placebo — DRUG
    twice daily (Q12H) oral dose

Study Details

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.

Key Dates

Start date
Jul 3, 2020
Status verified
Sep 2025
Primary completion
Mar 31, 2027
Completion
Mar 31, 2027

Study Design

Enrollment
600 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: CST-2 EIDD-2801 Phase Ib
    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.
  • No Intervention: CST-2 Control
    Phase 1b only (standard of care)
  • Placebo Comparator: CST-2 Placebo
    Phase II placebo blinded controlled
  • Experimental: CST-3A Nitazoxanide
    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
  • Experimental: CST-5 VIR-7832 Phase I
    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.
  • Active Comparator: CST-5 VIR-7831 Phase II
    Phase II: 500 mg dose of VIR-7831 will be given by IV infusion.
  • Placebo Comparator: CST-5 Placebo Phase I
    Phase I: placebo blinded controlled
  • Experimental: CST3B Nitazoxanide
    Phase II experimental arm.
  • No Intervention: CST3B Control
    Standard of care
  • Experimental: CST6 IV Favipiravir
    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.
  • No Intervention: CST6 Control
    Standard of care
  • Experimental: CST-2 EIDD-2801 Phase II
    EIDD-2801 (also known as MK-4482, molnupiravir). Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
  • Experimental: CST-8 Phase I Molnupiravir + Paxlovid®
    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.
  • No Intervention: CST-8 Phase I Molnupiravir + Paxlovid® Control
    Standard of care
  • Active Comparator: CST-5 VIR-7832
    Phase II: 500 mg dose of VIR-7832 will be given by IV infusion.
  • Placebo Comparator: CST-5 Placebo Phase II
    Phase II: placebo blinded controlled
  • Experimental: CST-9a Monotherapy
    Phase II: ALG-097558 600 mg twice a day orally for 5 days
  • Experimental: CST-9a Combination
    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)
  • Active Comparator: CST-9a Control
    Phase II : standard of care
  • Experimental: CST-9b: ALG-097558
    twice daily dose for 5 days
  • Placebo Comparator: CST-9b: placebo for ALG097558

Primary Outcome Measure

Master Protocol: Dose-finding/Phase I [ Time Frame: 29 days from randomisation ]

Central Contacts

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