Clinical trial NCT04746183: AGILE (Early Phase Platform Trial for COVID-19)
Official title: AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 Treatment
Conditions: Covid19
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.
Interventions:
description: 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.<br/>Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
name: CST-2: EIDD-2801
other_name: MK-4482
Molnupiravir
type: Drug
description: CST-2 Phase II: Placebo will be administered orally, twice daily (BID) for 10 doses (5 or 6 days).
name: CST-2: Placebo
other_name: Placebo
type: Drug
description: 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.<br/>Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
name: Nitazoxanide
type: Drug
description: 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.<br/>Phase II: As per Phase I, with the dose determined by the recommended phase II dose.
name: VIR-7832
type: Drug
description: CST-5 Phase II: A 500 mg dose of VIR-7831 will also be given by IV infusion over 1 hour.
name: VIR-7831
other_name: Sotrovimab
type: Drug
description: CST-5 Phase 1, Phase II: Placebo given by intravenous infusion over 1 hour
name: CST-5: Placebo
other_name: Placebo
type: Drug
description: 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).
name: Favipiravir
type: Drug
description: 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.
name: Molnupiravir
other_name: Lagevrio
type: Drug
description: Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days. The dose of Paxlovid® will be fixed for all cohorts.
name: Paxlovid
other_name: nirmatrelvir and ritonavir
type: Drug
description: ALG-097558 600 mg Twice a day (BD) for 5 days
name: ALG-097558
type: Drug
description: 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.
name: ALG-097558 and Remdesivir
other_name: ALG-097558 and veklury
type: Drug
description: NHS standard of care as per COVID-19 treatment guidelines
name: NHS standard of care as per COVID-19 treatment guidelines
other_name: any of the following: nirmatrelvir plus ritonavir (Paxlovid) sotrovimab (Xevudy) molnupiravir (Lagevrio)
type: Drug
description: twice daily (Q12H) oral dose of ALG-097558
name: ALG-097558
type: Drug
description: twice daily (Q12H) oral dose
name: Placebo
type: Drug
Study arms:
design_group_description: 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.
design_group_title: CST-2 EIDD-2801 Phase Ib
design_group_type: Experimental
design_group_description: Phase 1b only (standard of care)
design_group_title: CST-2 Control
design_group_type: No Intervention
design_group_description: Phase II placebo blinded controlled
design_group_title: CST-2 Placebo
design_group_type: Placebo Comparator
design_group_description: 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
design_group_title: CST-3A Nitazoxanide
design_group_type: Experimental
design_group_description: 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.
design_group_title: CST-5 VIR-7832 Phase I
design_group_type: Experimental
design_group_description: Phase II: 500 mg dose of VIR-7831 will be given by IV infusion.
design_group_title: CST-5 VIR-7831 Phase II
design_group_type: Active Comparator
design_group_description: Phase I: placebo blinded controlled
design_group_title: CST-5 Placebo Phase I
design_group_type: Placebo Comparator
design_group_description: Phase II experimental arm.
design_group_title: CST3B Nitazoxanide
design_group_type: Experimental
design_group_description: Standard of care
design_group_title: CST3B Control
design_group_type: No Intervention
design_group_description: 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.
design_group_title: CST6 IV Favipiravir
design_group_type: Experimental
design_group_description: Standard of care
design_group_title: CST6 Control
design_group_type: No Intervention
design_group_description: EIDD-2801 (also known as MK-4482, molnupiravir).<br/>Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.
design_group_title: CST-2 EIDD-2801 Phase II
design_group_type: Experimental
design_group_description: 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.
design_group_title: CST-8 Phase I Molnupiravir + Paxlovid®
design_group_type: Experimental
design_group_description: Standard of care
design_group_title: CST-8 Phase I Molnupiravir + Paxlovid® Control
design_group_type: No Intervention
design_group_description: Phase II: 500 mg dose of VIR-7832 will be given by IV infusion.
design_group_title: CST-5 VIR-7832
design_group_type: Active Comparator
design_group_description: Phase II: placebo blinded controlled
design_group_title: CST-5 Placebo Phase II
design_group_type: Placebo Comparator
design_group_description: Phase II: ALG-097558 600 mg twice a day orally for 5 days
design_group_title: CST-9a Monotherapy
design_group_type: Experimental
design_group_description: 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)
design_group_title: CST-9a Combination
design_group_type: Experimental
design_group_description: Phase II : standard of care
design_group_title: CST-9a Control
design_group_type: Active Comparator
design_group_description: twice daily dose for 5 days
design_group_title: CST-9b: ALG-097558
design_group_type: Experimental
design_group_title: CST-9b: placebo for ALG097558
design_group_type: Placebo Comparator
Sponsor: The University of Liverpool
Collaborators: University of Cambridge
Royal Liverpool Hospital
Liverpool School of Tropical Medicine
Drug name mappings:
name: 奈玛特韦/利托那韦
lang: CN
name: Nirmatrelvir/Ritonavir
lang: EN
name: ニルマトレルビル/リトナビル
lang: JP
name: 瑞德西韦
lang: CN
name: Remdesivir
lang: EN
name: レムデシビル
lang: JP
name: 硝唑尼特
lang: CN
name: Nitazoxanide
lang: EN
name: 法维拉韦
lang: CN
name: Favipiravir
lang: EN
name: ファビピラビル
lang: JP
name: ALG-097558
lang: EN
name: 莫诺拉韦
lang: CN
name: Molnupiravir
lang: EN
name: モルヌピラビル
lang: JP
name: VIR-7832
lang: EN