Status:
RECRUITING
AGILE (Early Phase Platform Trial for COVID-19)
Lead Sponsor:
University of Liverpool
Collaborating Sponsors:
Liverpool School of Tropical Medicine
Royal Liverpool University Hospital
Conditions:
Covid19
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
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...
Detailed 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 c...
Eligibility Criteria
Inclusion
- Master Protocol
- 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
- For the purpose of the EIDD-2801 candidate-specific trial the following inclusion criteria have been amended from the Master protocol to:
- 1\. 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) .
- 3\. 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).
- 4\. 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:
- 5\. Has signs or symptoms of COVID-19 that began within 5 days of the planned first dose of study drug.
- 6\. Is in generally good health (except for current respiratory infection) and is free of uncontrolled chronic conditions.
- 7\. Is willing and able to comply with all study procedures and attending clinic visits through the 4th week.
- 8\. Has someone, aged ≥ 16 living in the same household during the dosing period.
- CST-6 Additional inclusion criteria:
- 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)).
- Less than or equal to 14 days from onset of COVID-19 symptoms
- CST-8
- For the purpose of CST-8, criteria 1 has been amended from the Master Protocol to:
- Adults (≥18 years) outpatients positive lateral flow test at screening or baseline Day 1, who are within 5 days of symptom onset prior to the planned first dose of study drug.
- Criteria 3 has been amended from the Master Protocol to:
- Women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP must agree to use a highly effective method of contraception (as outlined in section 5.5 of the Master Protocol) for the duration of the treatment and for six weeks following the last dose.
- Additional criteria specific to CST-8 are:
- Initial onset of COVID-19 signs/symptoms within 5 days prior to the day of randomisation and at least 1 of the current specified COVID-19 signs/symptoms (listed on the NHS website) present on the day of randomisation
- Is willing and able to comply with all study procedures and attending clinic visits
- CST-9a
- For the purpose of CST-9a, criteria 1 has been amended from the Master Protocol to:
- Adults (\>/= 18 years of age) with a positive SARS-CoV-2 lateral flow test on screening or Day 1, who are at high risk (as defined in UK DHSC criteria) of progressing to severe COVID-19 disease, within 3 days of symptom onset, with at least one symptom of COVID-19 infection present on the day of randomization and are with mild- moderate disease severity at enrolment.
- Criterion 2 has been amended from the Master Protocol to:
- Ability to provide informed consent signed by trial participant or legally acceptable representative and are willing and able to comply with all trial procedures and attending clinic visits
- Criterion 3 has been amended from the Master Protocol to:
- Women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP must agree to use two effective methods of contraception, one of which must be highly effective for the duration of the treatment and for 90 Days following the last dose
- Master Protocol
Exclusion
- 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
Key Trial Info
Start Date :
July 3 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 31 2026
Estimated Enrollment :
600 Patients enrolled
Trial Details
Trial ID
NCT04746183
Start Date
July 3 2020
End Date
October 31 2026
Last Update
September 5 2025
Active Locations (6)
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1
Desmond Tutu Health Foundation
Cape Town, South Africa
2
Ezintsha
Johannesburg, South Africa
3
Liverpool University Hospitals NHS Foundation Trust
Liverpool, United Kingdom, L7 8XP
4
Kings College Hospital NHS Foundation Trust
London, United Kingdom