AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment. A randomised Phase I/II study to determine the safety and effectiveness of multiple drugs for the treatment of COVID-19
- Conditions
- Coronavirus-induced disease (COVID-19) (SARS coronavirus 2, or SARS-CoV-2)MedDRA version: 23.0Level: PTClassification code 10051905Term: Coronavirus infectionSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2020-001860-27-GB
- Lead Sponsor
- niversity of Liverpool
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 250
Master Protocol:
Patients are eligible to be included in the study only if all of the following criteria apply (as well as all criteria from the appropriate candidate-specific trial protocol):
1. Adults (=18 years) with laboratory-confirmed* SARS-CoV-2 infection (PCR)
2. Ability to provide informed consent signed by study patient or legally acceptable representative
3. Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use a highly effective method of contraception 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 candidate-specific trial protocol:
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) (as defined by the WHO Clinical Progression Scale.
Group B (mild-moderate disease)
4b. Ambulant or hospitalised patients with peripheral capillary oxygen saturation (SpO2) >94% RA.
Nomacopan Candidate-Specific Trial:
Additional inclusion criteria specific to this CST are:
1. Adults (=18 years) with laboratory-confirmed SARS-CoV-2 infection (PCR) who are within 5 days of symptom onset.
4. A score of grade 4, 5, 6 or 7 on the 9-Point Ordinal Scale*
Grade 6 and 7 will only be accepted when second cohort open to recruitment.
CST-2 (EIDD-2801) additional inclusion criteria:
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 weekly clinic visits through the 4th week.
8.Has someone, aged = 16 living in the same household during the dosing period.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
Master Protocol:
Patients are excluded from the study if any of the following criteria apply (as well as all criteria from the appropriate candidate-specific trial 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 breast feeding
4. Anticipated transfer to another hospital which is not a study site within 72 hours
5. Allergy to any study medication
6. Patients taking other prohibited drugs (as outline in CST protocol) within 30 days or 5 times the half-life (whichever is longer) of enrolment
7. Patients participating in another CTIMP trial
Nomacopan Candidate-Specific Trial:
For the purpose of the nomacopan candidate-specific trial, appendix exclusion criteria 6 has been amended from the Master protocol as follows, to restrict the population of patients that will be included in the trial:
6. Patients taking the following prohibited drugs:
• Other complement inhibiting drug such as eculizumab (Soliris®).
• Any other drug which directly inhibits cytokines, chemokines or proinflammatory mediators such as tocilizumab (Actemra®/RoActremra®), anakinra (Kineret®), etanercept (Enbrel®), infliximab (Remicade®) or adalimumab (Humira®).
N.B. Whilst it is not thought that there is likely to be any adverse interaction between nomacopan and any of these drugs, in the context of a clinical trial, it would be impossible to distinguish the effects of those agents from that of nomacopan. Corticosteroids, antivirals and antibiotics are permitted in conjunction with nomacopan therapy.
Additional exclusion criteria specific to this candidate specific appendix are:
8. Weight less than 50kg or more than 100kg
CST-2 (EIDD-2801) additional exclusion criteria:
8.Has a febrile respiratory illness that includes pneumonia that results in hospitalisation, or requires hospitalisation, oxygenation, mechanical ventilation, or other supportive modalities.
9.Has a platelet count less than 50x10^9/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 or maintenance steroids.
16.Has any condition that would, in the opinion of the investigator, put the patient at increased risk for participation in a clinical study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method