Health TrialsbyHealthPanel

AGILE (Early Phase Platform Trial for COVID-19)

ConditionCovid19
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Liverpool

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adults (≥18 years) with laboratory-confirmed* SARS-CoV-2 infection (PCR)

Ability to provide informed consent signed by study patient or legally acceptable representative

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.

Disqualifiers

Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 times the upper limit of normal (ULN)

Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration rate <30 mL/min/1.73 m²)

Pregnant or breast feeding

Anticipated transfer to another hospital which is not a study site within 72 hours

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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

Treatment groups

600 Participants
are divided into 21 treatment groups

21

Treatment groups

See each treatment group below.

Group A: CST-2 EIDD-2801 Phase IbExperimental treatment 1 intervention
Group B: CST-2 ControlNo intervention 0 interventions
Group C: CST-2 PlaceboPlacebo comparator 1 intervention
Group D: CST-3A NitazoxanideExperimental treatment 1 intervention
Group E: CST-5 VIR-7832 Phase IExperimental treatment 1 intervention
Group F: CST-5 VIR-7831 Phase IIActive comparator 1 intervention
Group G: CST-5 Placebo Phase IPlacebo comparator 1 intervention
Group H: CST3B NitazoxanideExperimental treatment 1 intervention
Group I: CST3B ControlNo intervention 0 interventions
Group J: CST6 IV FavipiravirExperimental treatment 1 intervention
Group K: CST6 ControlNo intervention 0 interventions
Group L: CST-2 EIDD-2801 Phase IIExperimental treatment 1 intervention
Group M: CST-8 Phase I Molnupiravir + Paxlovid®Experimental treatment 2 interventions
Group N: CST-8 Phase I Molnupiravir + Paxlovid® ControlNo intervention 0 interventions
Group O: CST-5 VIR-7832Active comparator 1 intervention
Group P: CST-5 Placebo Phase IIPlacebo comparator 1 intervention
Group Q: CST-9a MonotherapyExperimental treatment 1 intervention
Group R: CST-9a CombinationExperimental treatment 2 interventions
Group S: CST-9a ControlActive comparator 1 intervention
Group T: CST-9b: ALG-097558Experimental treatment 1 intervention
Group U: CST-9b: placebo for ALG097558Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Master Protocol: Dose-finding/Phase I

Determination of a dose(s) for efficacy evaluation. Dose limiting toxicities (Safety and Tolerability of drug under study - CTCAE v5 Grade ≥3 adverse events)

Time frame
29 days from randomisation
2

Master Protocol: Efficacy evaluation/Phase II - Severe patients (Group A)

Determination of activity and safety. In severe patients (Group A): time to clinical improvement. Improvement will be determined according to the WHO Clinical Progression Scale; improvement is defined as a minimum 2-step change from randomisation in the scale up to day 29 post-randomisation.

Time frame
29 days from randomisation
3

Master Protocol: Efficacy evaluation/Phase II - Mild to moderate patients (Group B)

Determination of activity and safety. In mild to moderate patients (Group B): pharmacodynamics of drug under study, defined as time to negative viral titres in nose and/or throat swab, measured up to 15 days post-randomisation.

Time frame
15 days from randomisation
4

CST-2 Phase I: To determine the safety and tolerability of multiple ascending doses of EIDD-2801 to recommend dose for phase II.

Dose limiting toxicity (DLT) using CTCAE version 5 (grades 3 and above) over 7 days. CTCAE grading related to platelets and/or lymphocytes

Time frame
7 days from randomisation

Secondary outcomes

1

Master Protocol: Safety assessed by rate of adverse events

Adverse event rate according to CTCAE v5

Time frame
Up to 29 days from randomisation
2

Master Protocol: To evaluate clinical improvement

Proportion of patients with clinical improvement (as defined above) at day 8, 15 and day 29.

Time frame
From randomisation to day 29
3

Master Protocol: To evaluate clinical improvement using WHO clinical progression scale

Change at day 8 and 15 from randomisation in the WHO Clinical Progression Scale

Time frame
From randomisation to day 15
4

Master Protocol: To evaluate clinical improvement using WHO clinical progression scale

Time to a one point change on the WHO Clinical Progression Scale

Time frame
From randomisation to day 29

Other outcomes

1

CST-8: Measure PK of nirmatrelvir and ritonavir in tears, saliva and nasal secretions

Concentration of nirmatrelvir and ritonavir in non-plasma

Time frame
From randomisation to Day 5
2

CST-8:To characterise genetic variability in SARS-CoV-2 before and during treatment via PCR analysis

PCR analysis re Baseline and treatment emergent genetic mutations in SARS-CoV-2

Time frame
From randomisation to Day 11
3

CST-9a: To characterise pharmacokinetics of ALG-097558 in tears, saliva, and nasal secretions

Concentration of ALG-097558 in non-plasma matrices

Time frame
day 1 to day 3
4

CST-9a: To characterise genetic variability in SARS-CoV-2 before and during treatment

Baseline and treatment emergent genetic mutations in SARS-CoV-2

Time frame
From randomisation to Day 11

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Liverpool

Lead sponsor

Liverpool School of Tropical Medicine

Collaborator

Royal Liverpool University Hospital

Collaborator

University of Cambridge

Collaborator

Source ClinicalTrials.gov
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