AGILE (Early Phase Platform Trial for COVID-19)

NCT04746183 | Recruiting Phase 1 DMC

• 1 other identifier: UoL001542i, UoL001542j
• Study Type: interventional
• Target: 600
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

Covid19

Keywords

SARS coronavirus 2; SARS-CoV-2; Phase I; Phase II; Platform trial

Outcome Measures

Primary Outcomes (15)

• 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)

  29 days from randomisation

• 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.

  29 days from randomisation

• 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.

  15 days from randomisation

• 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

  7 days from randomisation

• CST-2 Phase II: To determine the ability of EIDD-2801 to reduce serious complications of COVID-19 including hospitalization, reduction in SAO2<92%, or death.

  Progression of disease (SpO2\<92% based on at least 2 consecutive recordings on the same day) or hospitalization or death up to day 29

  29 days from randomisation

• CST6 Phase I: To determine the safety and tolerability of multiple doses of IV Favipiravir in patients with COVID-19

  Adverse events and serious adverse events

  29 days from randomisation

• CST6 Phase I: To determine the maximum safe dose of IV Favipiravir for efficacy evaluation in phase II

  Dose limiting toxicities (Safety and Tolerability of IV Favipiravir- CTCAE v5 Grade ≥3 adverse events)

  8 days from randomisation

• CST-8 Phase I: Dose Limiting Toxicities up to and including Day 11

  Dose limiting toxicities (Safety and Tolerability of molnupiravir and Paxlovid® combination - CTCAE v5 Grade ≥3 adverse events) up to and including Day 11

  11 days from randomisation

• CST-9a: Dose limiting toxicities up to and including Day 11

  Dose limiting toxicities (Safety and Tolerability of ALG-097558 and ALG-097558 plus remdesivir combination - CTCAE v5 Grade ≥3 adverse events) up to and including Day 11

  11 days from randomisation

• CST-9a: to determine the safety and tolerability of ALG-097558 and ALG-097558 plus remdesivir combination

  Adverse events, serious adverse events, physical findings, vital signs, ECG and laboratory parameters

  11 days from randomisation

• CST-9a: Change in viral titre overtime following administration of ALG-097558 alone and in combination with RDV versus Standard of Care (SoC)

  Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nose and throat swab

  11 days from randomisation

• CST-9a: Sustained symptom resolution

  Symptom resolution evaluated through questionnaires

  29 days from randomisation

• CST-9b

  AEs, SAEs

  11 Days from randomisation

• CST-9b

  Dose Limiting Toxicity (DLT) using CTCAE version 5 (grades 3 and above) up to and including Day 11

  11 days from randomisation

• CST-9b

  Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nose and throat swab

  11 days from randomisation

Secondary Outcomes (50)

• Master Protocol: Safety assessed by rate of adverse events

  Up to 29 days from randomisation

• Master Protocol: To evaluate clinical improvement

  From randomisation to day 29

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

  From randomisation to day 15

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

  From randomisation to day 29

• Master Protocol: To evaluate clinical improvement using SpO2/FiO2

  From randomisation to day 29

Other Outcomes (6)

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

  From randomisation to Day 5

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

  From randomisation to Day 11

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

  day 1 to day 3

Study Arms (21)

CST-2 EIDD-2801 Phase Ib

EXPERIMENTAL

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.

Drug: CST-2: EIDD-2801

CST-2 Control

NO INTERVENTION

Phase 1b only (standard of care)

CST-2 Placebo

PLACEBO COMPARATOR

Phase II placebo blinded controlled

Drug: CST-2: Placebo

CST-3A Nitazoxanide

EXPERIMENTAL

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

Drug: Nitazoxanide

CST-5 VIR-7832 Phase I

EXPERIMENTAL

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.

Drug: VIR-7832

CST-5 VIR-7831 Phase II

ACTIVE COMPARATOR

Phase II: 500 mg dose of VIR-7831 will be given by IV infusion.

Drug: VIR-7831

CST-5 Placebo Phase I

PLACEBO COMPARATOR

Phase I: placebo blinded controlled

Drug: CST-5: Placebo

CST3B Nitazoxanide

EXPERIMENTAL

Phase II experimental arm.

Drug: Nitazoxanide

CST3B Control

NO INTERVENTION

Standard of care

CST6 IV Favipiravir

EXPERIMENTAL

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.

Drug: Favipiravir

CST6 Control

NO INTERVENTION

Standard of care

CST-2 EIDD-2801 Phase II

EXPERIMENTAL

EIDD-2801 (also known as MK-4482, molnupiravir). Phase II: As per Phase Ib, with the dose determined by the recommended phase II dose.

Drug: CST-2: EIDD-2801

CST-8 Phase I Molnupiravir + Paxlovid®

EXPERIMENTAL

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.

Drug: Molnupiravir; Drug: Paxlovid

CST-8 Phase I Molnupiravir + Paxlovid® Control

NO INTERVENTION

Standard of care

CST-5 VIR-7832

ACTIVE COMPARATOR

Phase II: 500 mg dose of VIR-7832 will be given by IV infusion.

Drug: VIR-7832

CST-5 Placebo Phase II

PLACEBO COMPARATOR

Phase II: placebo blinded controlled

Drug: CST-5: Placebo

CST-9a Monotherapy

EXPERIMENTAL

Phase II: ALG-097558 600 mg twice a day orally for 5 days

Drug: ALG-097558

CST-9a Combination

EXPERIMENTAL

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)

Drug: ALG-097558; Drug: ALG-097558 and Remdesivir

CST-9a Control

ACTIVE COMPARATOR

Phase II : standard of care

Drug: NHS standard of care as per COVID-19 treatment guidelines

CST-9b: ALG-097558

EXPERIMENTAL

twice daily dose for 5 days

Drug: ALG-097558

CST-9b: placebo for ALG097558

PLACEBO COMPARATOR

Drug: Placebo

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.

Also known as: MK-4482, Molnupiravir

CST-2 EIDD-2801 Phase II; CST-2 EIDD-2801 Phase Ib

Placebo DRUG

twice daily (Q12H) oral dose

CST-9b: placebo for ALG097558

CST-2: Placebo DRUG

CST-2 Phase II: Placebo will be administered orally, twice daily (BID) for 10 doses (5 or 6 days).

Also known as: Placebo

CST-2 Placebo

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.

CST-3A Nitazoxanide; CST3B Nitazoxanide

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.

CST-5 VIR-7832; CST-5 VIR-7832 Phase I

VIR-7831 DRUG

CST-5 Phase II: A 500 mg dose of VIR-7831 will also be given by IV infusion over 1 hour.

Also known as: Sotrovimab

CST-5 VIR-7831 Phase II

CST-5: Placebo DRUG

CST-5 Phase 1, Phase II: Placebo given by intravenous infusion over 1 hour

Also known as: Placebo

CST-5 Placebo Phase I; CST-5 Placebo Phase II

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).

CST6 IV Favipiravir

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.

Also known as: Lagevrio

CST-8 Phase I Molnupiravir + Paxlovid®

Paxlovid DRUG

Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days. The dose of Paxlovid® will be fixed for all cohorts.

Also known as: nirmatrelvir and ritonavir

CST-8 Phase I Molnupiravir + Paxlovid®

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.

Also known as: ALG-097558 and veklury

CST-9a Combination

NHS standard of care as per COVID-19 treatment guidelines DRUG

NHS standard of care as per COVID-19 treatment guidelines

Also known as: any of the following: nirmatrelvir plus ritonavir (Paxlovid) sotrovimab (Xevudy) molnupiravir (Lagevrio)

CST-9a Control

ALG-097558 DRUG

ALG-097558 600 mg Twice a day (BD) for 5 days

CST-9a Combination; CST-9a Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Standard additional criteria that may be applied per CST protocol:
• Group A (severe disease) 4a. Patients with clinical status of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, on non-invasive ventilation, or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (ventilation and additional organ support - pressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO)), as defined by the WHO clinical severity score, 9-point ordinal scale.
• \. Male or female ≥ 60 years old or ≥50 years old with at least one well controlled comorbidity: cardiovascular disease, chronic lung disease (e.g. COPD, or pulmonary hypertension), immune deficiency (taking the equivalent of 20 mg prednisone daily, chemotherapy, or immune modulating biologic therapies), diabetes (treated with insulin or oral medications), BMI≥30, or hypertension requiring medication with laboratory confirmed SARS-CoV-2 infection (PCR) .
• \. Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use two effective methods of contraception, one of which should be highly effective (as outlined in the protocol). For women, from the first administration of trial treatment, throughout trial and up to 50 days after the last follow up visit (50 days after day 29) and for men with female partners of child bearing potential, from the first administration until 100 days after last follow up visit (100 days after day 29).
• \. Group B (mild-moderate disease): Ambulant with the following characteristics peripheral capillary oxygen saturation (SpO2) \>94% RA (NB this differs to the Master Protocol which also includes hospitalised patients in this group).
• Additional criteria specific to this candidate are:
• \. Has signs or symptoms of COVID-19 that began within 5 days of the planned first dose of study drug.
• \. Is in generally good health (except for current respiratory infection) and is free of uncontrolled chronic conditions.
• \. Is willing and able to comply with all study procedures and attending clinic visits through the 4th week.
• \. Has someone, aged ≥ 16 living in the same household during the dosing period.
• Group A (severe disease). Patients with clinical status of Grades 5 (hospitalised, oxygen by mask or nasal prongs), 6 (hospitalised, on non-invasive ventilation, or high flow oxygen as defined by the WHO Clinical Progression Scale (WHO, 2020)).

You may not qualify if:

• 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 m\^2)
• Pregnant or breast feeding
• Anticipated transfer to another hospital which is not a study site within 72 hours
• Allergy to any study medication
• Patients taking other prohibited drugs (as outline in CST protocol) within 30 days or 5 times the half-life (whichever is longer) of enrolment
• Patients participating in another CTIMP trial
• Prior SARS-CoV-2 infection \<90 days before enrolment and/or received any COVID-19 vaccine dose \<90 days before enrolment
• Alanine aminotransferase (ALT) \>3 times the upper limit of normal (ULN) or Active Liver disease
• History or current evidence of cirrhosis
• Receiving dialysis or have known moderate to severe renal impairment (defined as CKD stage 4 or 5) or current acute kidney injury on most recent eGFR in the past 6 months
• Pregnant or breast feeding
• Anticipated transfer to another hospital which is not a trial site within 72 hours
• Known allergy to any trial medication
• Swallowing difficulties

Sponsors & Collaborators

• University of Liverpool: lead
• Liverpool School of Tropical Medicine: collaborator
• Royal Liverpool University Hospital: collaborator
• University of Cambridge: collaborator

Study Sites (7)

Desmond Tutu Health Foundation

Cape Town, South Africa

COMPLETED

Ezintsha

Johannesburg, South Africa

COMPLETED

Liverpool University Hospitals NHS Foundation Trust

Liverpool, L7 8XP, United Kingdom

RECRUITING

Kings College Hospital NHS Foundation Trust

London, United Kingdom

ACTIVE NOT RECRUITING

Royal Free Hospital

London, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

RECRUITING

Related Publications (8)

• Griffiths G, Fitzgerald R, Jaki T, Corkhill A, Marwood E, Reynolds H, Stanton L, Ewings S, Condie S, Wrixon E, Norton A, Radford M, Yeats S, Robertson J, Darby-Dowman R, Walker L, Khoo S; UK NIHR community. AGILE-ACCORD: A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19: A structured summary of a study protocol for a randomised platform trial. Trials. 2020 Jun 19;21(1):544. doi: 10.1186/s13063-020-04473-1.

  PMID: 32560744 BACKGROUND

• Griffiths GO, FitzGerald R, Jaki T, Corkhill A, Reynolds H, Ewings S, Condie S, Tilt E, Johnson L, Radford M, Simpson C, Saunders G, Yeats S, Mozgunov P, Tansley-Hancock O, Martin K, Downs N, Eberhart I, Martin JWB, Goncalves C, Song A, Fletcher T, Byrne K, Lalloo DG, Owen A, Jacobs M, Walker L, Lyon R, Woods C, Gibney J, Chiong J, Chandiwana N, Jacob S, Lamorde M, Orrell C, Pirmohamed M, Khoo S; AGILE investigators. AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter. Trials. 2021 Jul 26;22(1):487. doi: 10.1186/s13063-021-05458-4.

  PMID: 34311777 BACKGROUND

• Khoo SH, Fitzgerald R, Fletcher T, Ewings S, Jaki T, Lyon R, Downs N, Walker L, Tansley-Hancock O, Greenhalf W, Woods C, Reynolds H, Marwood E, Mozgunov P, Adams E, Bullock K, Holman W, Bula MD, Gibney JL, Saunders G, Corkhill A, Hale C, Thorne K, Chiong J, Condie S, Pertinez H, Painter W, Wrixon E, Johnson L, Yeats S, Mallard K, Radford M, Fines K, Shaw V, Owen A, Lalloo DG, Jacobs M, Griffiths G. Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study. J Antimicrob Chemother. 2021 Nov 12;76(12):3286-3295. doi: 10.1093/jac/dkab318.

  PMID: 34450619 RESULT

• Walker LE, FitzGerald R, Saunders G, Lyon R, Fisher M, Martin K, Eberhart I, Woods C, Ewings S, Hale C, Rajoli RKR, Else L, Dilly-Penchala S, Amara A, Lalloo DG, Jacobs M, Pertinez H, Hatchard P, Waugh R, Lawrence M, Johnson L, Fines K, Reynolds H, Rowland T, Crook R, Okenyi E, Byrne K, Mozgunov P, Jaki T, Khoo S, Owen A, Griffiths G, Fletcher TE; AGILE platform. An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2. Clin Pharmacol Ther. 2022 Mar;111(3):585-594. doi: 10.1002/cpt.2463. Epub 2021 Nov 13.

  PMID: 34699618 RESULT

• Khoo SH, FitzGerald R, Saunders G, Middleton C, Ahmad S, Edwards CJ, Hadjiyiannakis D, Walker L, Lyon R, Shaw V, Mozgunov P, Periselneris J, Woods C, Bullock K, Hale C, Reynolds H, Downs N, Ewings S, Buadi A, Cameron D, Edwards T, Knox E, Donovan-Banfield I, Greenhalf W, Chiong J, Lavelle-Langham L, Jacobs M, Northey J, Painter W, Holman W, Lalloo DG, Tetlow M, Hiscox JA, Jaki T, Fletcher T, Griffiths G; AGILE CST-2 Study Group. Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Infect Dis. 2023 Feb;23(2):183-195. doi: 10.1016/S1473-3099(22)00644-2. Epub 2022 Oct 19.

  PMID: 36272432 RESULT

• FitzGerald R, Dickinson L, Else L, Fletcher T, Hale C, Amara A, Walker L, Penchala SD, Lyon R, Shaw V, Greenhalf W, Bullock K, Lavelle-Langham L, Reynolds H, Painter W, Holman W, Ewings S, Griffiths G, Khoo S. Pharmacokinetics of ss-d-N4-Hydroxycytidine, the Parent Nucleoside of Prodrug Molnupiravir, in Nonplasma Compartments of Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Clin Infect Dis. 2022 Aug 24;75(1):e525-e528. doi: 10.1093/cid/ciac199.

  PMID: 35271729 RESULT

• Donovan-Banfield I, Penrice-Randal R, Goldswain H, Rzeszutek AM, Pilgrim J, Bullock K, Saunders G, Northey J, Dong X, Ryan Y, Reynolds H, Tetlow M, Walker LE, FitzGerald R, Hale C, Lyon R, Woods C, Ahmad S, Hadjiyiannakis D, Periselneris J, Knox E, Middleton C, Lavelle-Langham L, Shaw V, Greenhalf W, Edwards T, Lalloo DG, Edwards CJ, Darby AC, Carroll MW, Griffiths G, Khoo SH, Hiscox JA, Fletcher T. Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial. Nat Commun. 2022 Nov 26;13(1):7284. doi: 10.1038/s41467-022-34839-9.

  PMID: 36435798 RESULT

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

Related Links

• The AGILE Clinical Trial Platform website

MeSH Terms

Conditions

COVID-19

Interventions

molnupiravir; nitazoxanide; VIR-7832; sotrovimab; favipiravir; nirmatrelvir and ritonavir drug combination; remdesivir; Ritonavir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Saye Khoo

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helen E Reynolds

CONTACT

+44 (0)1517945553; livagile@liv.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: CST-2: Phase I, open-label EIDD-2801 vs standard of care. Phase II, blinded controlled parallel group of EIDD-2801 vs placebo CST-3A: Phase Ia, open-label nitazoxanide CST-3B: Phase Ib, II, open label nitazoxanide vs standard of care CST-5: Phase I, blinded VIR-7832 vs placebo, Phase II, blinded VIR-7832 vs VIR-7831 vs placebo CST-6: Open label IV favipiravir vs standard of care CST-8: Open label Molnupiravir and Paxlovid® versus standard of care CST-9a: Open label ALG-097558 versus ALG-097558 + remdesivir versus standard of care CST-9b:Double Blind ALG-097558 versus matching placebo for ALG097558
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: CST2: Closed CST3A: Closed CST3B: Closed CST5: Closed CST6: Closed CST8: Closed CST9a:1:1:1 randomised open label Phase II of ALG-097558 versus ALG-097558+ remdesivir VS SOC CST9b: Double Blind 1:1 stratified randomised controlled adaptive trial with twice daily (Q12H) oral dose of ALG-097558 versus matching placebo for ALG097558.

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: February 9, 2021
• Study Start: July 3, 2020
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: June 1, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Master protocol published 19 June 2020
• Access Criteria: Master protocol available from https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04473-1

Locations

ZA (2); GB (5)