Ask to take part

Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.

Contact Information:

Dr Richard Fitzgerald
-
Agile@liverpoolft.nhs.uk


Prof Saye Khoo
+44 (0)151 794 5560
LivAGILE@liverpool.ac.uk


More information about this study, what is involved and how to take part can be found on the study website.

Study Location:

Find another location


Questions to ask
Skip to Main Content
English | Cymraeg
Be Part of Research - Trial Details - A study to assess several different treatments that may be useful for patients with COVID-19
Back

A study to assess several different treatments that may be useful for patients with COVID-19

Recruiting

Open to: All Genders

Age: Adult

Manchester Southampton Liverpool

Medical Conditions

COVID-19 (SARS-CoV-2 infection)

This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.


COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.

In 2020, the virus had spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimise travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.

The AGILE study aims to assess several different treatments that may be useful for patients with COVID-19. These treatments have been recommended for testing by a team of experts (the AGILE Scientific Advisory Board) based on strict criteria.
The aims of this study are to determine, in people with COVID-19, the following:
• The safety of the study drug and any side effects that might be associated with it
• How much of the study drug gets into the bloodstream
• How quickly the body removes the study drug and its active ingredients once the body has processed it
• How well the study drug might be able to reduce complications of COVID-19

Although these treatments show promise, nobody knows if any of them will turn out to be more effective in helping patients recover than the standard of care at home as recommended by their doctor (which all patients currently receive).
The treatment being assessed in Candidate Specific Trial Protocols, of which currently there is no active and recruiting trials (as of Jan 2024), and CST-9 is at the planning stage.

CST-2:
A Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the optimal dose, Safety and Efficacy of EIDD-2801 (molnupiravir) for the Treatment of COVID-19

CST-3A:
A Multicentre, Adaptive, Phase I trial to Determine the optimal dose, Safety and Efficacy of Nitazoxanide for the Treatment of COVID-19

CST-3B:
A Multicentre, Adaptive, Phase I/II trial to Determine the optimal dose, Safety and Efficacy of Nitazoxanide for the Treatment of COVID-19

CST-5:
A Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the Phase II dose of VIR-7832, and Evaluate the Safety and Efficacy of VIR-7831 and VIR-7832 for the Treatment of COVID-19

CST-6:
A Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the Phase II dose and to Evaluate the Safety and Efficacy of intravenous Favipiravir for the Treatment of COVID-19

CST-8:
A Randomised, Multicentre, Seamless, Adaptive, Phase I Platform Study to Determine the recommended Phase II dose and Evaluate the Safety and Efficacy of an antiviral combination of Molnupiravir and Paxlovid® for the Treatment of COVID-19

CST-9:
A Multicentre, Adaptive Phase II Platform Trial to Evaluate the Safety, Efficacy and Virological response of ALG-097558 as monotherapy and in combination with Remdesivir in high-risk population for the Treatment of COVID-19 disease.

Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.  

The recruitment start and end dates are as follows:

08 Mar 2020 31 Jul 2025

Publications

2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/32560744/ protocol (added 03/12/2020)2022 Results article in https://pubmed.ncbi.nlm.nih.gov/36272432/ 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 (added 24/10/2022)

CST-2:
Patients will take EIDD-2801 (molnupiravir) versus the standard of care to confirm an optimal dose for the study during Phase I. For Phase II, patients will be given study drug or placebo to determine the ability of study drug to improve viral clearance.

CST-3A:
Patients will be given 1500mg of nitazoxanide twice daily for 7 days to determine the safety and optimum dosing schedule in healthy volunteers.

CST-3B:
The Phase Ib drug dose was informed by the CST-3A study and is currently 1500mg BID. The phase Ib is complete and will be reviewed by the Safety Review Committee (SRC). The Safety Review Committee will determine the Phase II dosing requirement.
CST-5: Doses of VIR-7832 or placebo will be administered via IV infusion to patients in doses of 50mg, 150mg or 500mg followed by a Phase II of VIR-7832 versus VIR-7831 versus placebo.

CST-6:
Phase I: 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). Duration of monitoring will be 29 days post-first dose.

CST-8:
Molnupiravir 800mg twice a day (BD) in combination with Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days as starting dose, versus standard of care, 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.

CST-9:
Twice daily dose of ALG-097558 (monotherapy arm) versus the twice daily dose of ALG-097558 in combination with RDV (combination arm) versus standard-of-care therapy (SoC arm) with an early futility analysis.

Full details of the specific visits and the procedures are included in the current versions of the patient information sheet for each candidate study.


To be eligible for the Agile study, there’s a variety of inclusion and exclusion criteria dictated by the Master Protocol of Agile, however, each candidate will have their own inclusion and exclusion criteria dictated in its own separate protocol.
Inclusion Criteria: Adult patients (≥18 years) who have confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Group A (severe disease): Patients with clinical status of Grades 5 (hospitalised, oxygen by mask or nasal prongs), 6 (hospitalised, non-invasive ventilation or high flow oxygen), 7 (hospitalised, intubation and mechanical ventilation, pO2/FiO2 ≥150 or SpO2/FiO2 ≥200), 8 (hospitalised mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors or 9 (hospitalised, mechanical ventilation pO2/FiO2 <150 and vasopressors, dialysis or ECMO).
Group B (mild-moderate disease): Ambulant or hospitalised patients with peripheral capillary oxygen saturation (SpO2) >94% RA
N.B. If any Candidate Specific Trials (CST) are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible (e.g. ICD-10 U0.71 COVID-19).
We will also include healthy volunteers as a separate group: Group C (Healthy Volunteers)

You can take part if:



You may not be able to take part if:


Patients are excluded from the study if any of the following criteria apply (as well as all criteria from the appropriate CST protocol):1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 times the upper limit of normal (ULN)2. Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration rate <30 ml/min/1.73 m²)3. Pregnant or breastfeeding4. Anticipated transfer to another hospital which is not a study site within 72 hours5. Allergy to any study medication6. Patients taking other prohibited drugs (as outline in CST protocol) within 30 days or 5 times the half-life (whichever is longer) of enrolment7. Patients participating in another CTIMP trialN.B. The CST protocol exclusion criteria will take precedence over the master protocol exclusion criteria.Additional criteria specific to Candidate Specific Trial (CST-2) as of 30/11/2020 are:* The master protocol stipulates ‘Exclusion Criteria 4’ as ‘anticipated transfer to another hospital which is not a study site within 72 hours’. This is not applicable to this protocol as patients are expected to be out-patients.8. Has a febrile respiratory illness that includes pneumonia that result in hospitalisation, or requires hospitalisation, oxygenation, mechanical ventilation, or other supportive modalities.9. Has a platelet count less than 50x109/L.10. Is experiencing adverse events or laboratory abnormalities that are Grade 3 or above based on the CTCAE v5 grading.11. Has clinically significant liver dysfunction or renal impairment.12. Has history of hepatitis C infection or concurrent bacterial pneumonia.13. Has received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 30 days prior to the first dose of study drug.14. In the opinion of the investigator, has significant end-organ disease as a result of relevant comorbidities: chronic kidney disease, congestive heart failure, peripheral vascular disease including diabetic ulcers.15. Has a SaO₂ <95% by oximetry or has lung disease that requires supplemental oxygen.16. Has any condition that would, in the opinion of the investigator, put the patient at increased risk for participation in a clinical study.


Below are the locations for where you can take part in the trial. Please note that not all sites may be open.

  • Central Manchester University Hospitals NHS Foundation Trust
    Trust Headquarters, Cobbett House Manchester Royal Infirmary Oxford Road
    Manchester
    M13 9WL
  • Southampton General Hospital Clinical Research Facility
    Southampton General Hospital Tremona Road
    Southampton
    SO16 6YD
  • NHS University Hospitals of Liverpool Group
    Royal Liverpool University Hospital Prescot Street
    Liverpool
    L7 8XP

We do not know if the treatments being tested will be therapeutic (have a beneficial effect) or help with the symptoms of COVID-19, but this study should help inform how we treat future patients.
EIDD-2801 (molnupiravir) is being developed for the treatment of infections caused by highly pathogenic coronaviruses, including SARS-CoV-2. As of 20th March 2021, following completion of the Phase I study analysis with no evidence of Dose dose-limiting toxicities and DMEC review of data relating to the first 60 patients in Phase II, no significant safety concerns have been demonstrated for EIDD-2801 and, consequently, there is no requirement for updates to the risk assessment or monitoring plan.
The purpose of this study is to determine if taking nitazoxanide is safe at frequent and higher dosing over a longer treatment period. Therefore, there are no benefits to taking part in this study. Higher single doses of nitazoxanide (up to 4000 mg) have previously been given to people in other clinical trials. The maximum nitazoxanide dose that will be given in this study will be
3500 mg per day. It is not known whether higher doses of nitazoxanide, given for 7 days, will increase its side effects. However, you will be closely monitored for any side effects during the clinical trial.
The possible benefits are improvements to the patient’s condition (COVID-19). The possible risks are potential gastrointestinal issues, such as diarrhoea and nausea.
We do not know if the treatment being tested will be therapeutic (have a beneficial effect) or help you with your symptoms, but this study should help inform how we treat future patients. VIR-7832 works by blocking the virus from entering the body’s cells so it cannot make more of itself. VIR-7832 has been extensively tested in monkeys and it was well tolerated in monkeys up to a 600-fold higher dose than the dose being tested in the first dose group (cohort). VIR-7832 has been administered to 18 participants during the first phase of the study and was well tolerated by the participants. Due to the small number of participants who have had the drug, there is still limited information about its effects and side effects and VIR-7832 may have side effects that are currently unknown.
There is a remote chance that the study drug (like any drug product) may cause an allergic reaction, which in some cases may be severe. This is known as an anaphylactic reaction. An anaphylactic reaction may require emergency treatment. Report any unusual signs or symptoms you notice to the Unit medical staff straight away.
Similarly to VIR-7832, VIR-7831 is a monoclonal antibody, a type of protein designed to recognise a specific target on the SARS-CoV-2 virus, the virus that causes acute COVID-19 infection. It is approved by the NHS and used to treat symptomatic acute COVID-19 infection in adults and adolescents (from 12 years and weighing at least 40kg).
If there are any changes to the potential risks associated with the study drug during the study, patients will be informed by the study doctor. Patients may also experience other unwanted effects or discomforts with the study procedures. Full details of the risks of the study drug and procedures are included in the current version of the patient information sheet.
Favipiravir, the drug under investigation, is already used in tablet form as a treatment for influenza. In this study, the drug will be formulated as a liquid suitable for hospital use in an intravenous drip. By directly injecting it into the cells (intracellular), the drug may be more potent. This may potentially benefit patients already in hospital with Covid.
However, the novel liquid formulation has not been tested, and the optimum dosage is unknown. The present Phase I aims to identify this, with Phase II further investigating the safety and efficacy of this drug.
The possible benefits are a reduced risk of hospitalisation or death.
Each of the drugs in the combination, when used individually, are drugs are currently licensed for the treatment of mild to moderate coronavirus disease (Covid-19), however, there is limited information about the use of the drugs in combination. This Phase I study aims to establish a safe dose that can be used in further research in a larger Phase II study.
This Phase II study aims to determine the safety and tolerability of ALG-097558 alone and in combination with the nucleoside analogue Remdesivir (RDV). ALG-097558 of 600 mg twice daily (Q12H) for 5 days in this study may result in clinically meaningful efficacy outcomes (e.g., shorter time to symptom resolution, reduction in viral load) in high-risk subjects with acute SARS-CoV-2 infection.

Prof Saye Khoo
+44 (0)151 794 5560
LivAGILE@liverpool.ac.uk


Dr Richard Fitzgerald
-
Agile@liverpoolft.nhs.uk



More information about this study, what is involved and how to take part can be found on the study website.


The study is sponsored by University of Liverpool and funded by NIHR Southampton Clinical Trials Unit; Ridgeback Biotherapeutics; National Institute for Health Research; Unitaid; GlaxoSmithKline; Vir Biotechnology; Medical Research Council; Department of Health and Social Care; Wellcome Trust; Aligos Therapeutics.



We'd like your feedback

Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.


Is this study information helpful?

What will you do next?
Read full details for Trial ID: ISRCTN27106947

Or CPMS 45759

Last updated 20 November 2024

This page is to help you find out about a research study and if you may be able to take part

You can print or share the study information with your GP/healthcare provider or contact the research team directly.   

Back to the top