AGILE (Early Phase Platform Trial for COVID-19)

  • STATUS
    Recruiting
  • End date
    Apr 30, 2022
  • participants needed
    600
  • sponsor
    University of Liverpool
Updated on 4 September 2021

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 determined by the AGILE Scientific Advisory Board based on pre-clinical data, evidence in the clinical setting and GMP capabilities.

Description

AGILE is a multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II Bayesian randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19.

This study allows for the assessment of many candidates at different doses, with the ability to add candidates as they are identified or drop them as their evaluation is completed. Promising candidates will move to the an external trial for further evaluation in the phase II/III setting.

Each candidate will be evaluated in its own trial, randomising between candidate and control with 2:1 allocation in favour of the candidate. Each dose will be assessed for safety sequentially in cohorts of 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort.

AGILE is completely flexible in that the core design in the master protocol (as has been explained above) can be adapted for each candidate based on prior knowledge of the candidate

  • i.e. population, primary endpoint and sample size can be amended. This will be detailed in each candidate-specific trial protocol of the master protocol.

Candidate-Specific Trial 1 (CST-1): TBC

Candidate-Specific Trial 2 (CST-2): Open-label 2:1 randomised controlled phase I of EIDD-2801 versus standard of care followed by a 1:1 blinded controlled parallel group Phase II trial of EIDD-2801 versus placebo. A phase I will be carried out to confirm the optimal dose in this group. Following a safety review, EIDD-2801 will be tested for efficacy in a blinded placebo controlled randomised phase II trial.

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

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

Candidate-Specific Trial 5 (CST-5): 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

Details
Condition COVID19
Treatment Nitazoxanide, VIR-7831, CST-2: EIDD-2801, CST-2: Placebo, VIR-7832, CST-5: Placebo
Clinical Study IdentifierNCT04746183
SponsorUniversity of Liverpool
Last Modified on4 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Group B (mild-moderate disease) 4b. Ambulant or hospitalised patients with the
following characteristics peripheral capillary oxygen saturation (SpO2) >94%
RA N.B. The CST protocol inclusion criteria will take precedence over the
master protocol inclusion criteria
CST-2 Inclusion Criteria
For the purpose of the EIDD-2801 candidate-specific trial the following
inclusion criteria have been amended from the Master protocol to
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), BMI30, 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

Exclusion Criteria

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
N.B. The CST protocol exclusion criteria will take precedence over the master
protocol exclusion criteria
CST-2 Exclusion Criteria
Additional criteria specific to this candidate are
\. Has a febrile respiratory illness that includes signs of pneumonia, or
requires hospitalization, oxygenation, mechanical ventilation, or other
supportive modalities
\. Has a platelet count less than 50x10^9/L, or lymphocytes less than
2x10^9/L, haemoglobin less than 10 g/dL, or has a disorder of the
hematologic system including anaemic disorder or other blood dyscrasia, cancer
of the hematologic system, history of bone marrow transplant, or other
significant hematologic disease at screening
\. Is experiencing adverse events or laboratory abnormalities that are Grade
or above based on the CTCAE scale
\. Has clinically significant liver dysfunction or renal impairment
\. Has history of Hepatitis C infection or concurrent bacterial pneumonia
\. Has received an experimental agent (vaccine, drug, biologic, device
blood product, or medication) within 30 days prior to the first dose of study
drug
\. 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
\. Has a SaO2<95% by oximetry or has lung disease that requires supplemental
oxygen
\. Has any condition that would, in the opinion of the investigator, put the
patient at increased risk for participation in a clinical study
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