AGILE (Early Phase Platform Trial for COVID-19)

Covid19 Clinical Trial

Official title:

AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04746183
• Other study ID #: UoL001542
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 3, 2020
• Est. completion date: April 30, 2024

Study information

• Verified date: November 2023
• Source: University of Liverpool
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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

Candidate-Specific Trial 6 (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

Candidate-Specific Trial 8 (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 antiviral combination of Molnupiravir and Paxlovid® for the Treatment of COVID-19

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. completion date: April 30, 2024
• Est. primary completion date: December 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Master Protocol Inclusion Criteria:

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 (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:

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:

1. 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)).

2. Less than or equal to 14 days from onset of COVID-19 symptoms

CST-8 Inclusion Criteria:

1. 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.

2. 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

Master Protocol Exclusion Criteria:

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 m^2)

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

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:

8. Has a febrile respiratory illness that includes signs of pneumonia, or requires hospitalization, oxygenation, mechanical ventilation, or other supportive modalities.

9. Has a platelet count less than 50x10^9/L, or lymphocytes less than 0.2x10^9/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.

10. Is experiencing adverse events or laboratory abnormalities that are Grade 3 or above based on the CTCAE scale.

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.

CST-8 Exclusion Criteria:

For the purpose of the combination CST8 candidate-specific trial the following exclusion criteria also apply:

1. Swallowing difficulties

2. Known medical history of active liver disease

3. Receiving dialysis or have known moderate to severe renal impairments (defined as CKD stage 4 or 5 or current acute kidney injury or most recent eGFR in the past 6 months <30 ml/min/1.73m2)

4. Currently taking Paxlovid® or molnupiravir at time of screening

5. Oxygen saturation of <92% on room air, or on their standard home oxygen supplementation

6. Taking a drug which would put subject at unacceptable risk due to interaction or is contraindicated as per SPC for each IMP

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• CST-2: EIDD-2801
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.
• CST-2: Placebo
CST-2 Phase II: Placebo will be administered orally, twice daily (BID) for 10 doses (5 or 6 days).
• Nitazoxanide
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.
• VIR-7832
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.
• VIR-7831
CST-5 Phase II: A 500 mg dose of VIR-7831 will also be given by IV infusion over 1 hour.
• CST-5: Placebo
CST-5 Phase 1, Phase II: Placebo given by intravenous infusion over 1 hour
• Favipiravir
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).
• Molnupiravir
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.
• Paxlovid
Paxlovid® (300mg nirmatrelvir + ritonavir 100mg) twice a day (BD) for 5 days. The dose of Paxlovid® will be fixed for all cohorts.

Locations

Country	Name	City	State
South Africa	Desmond Tutu Health Foundation	Cape Town
South Africa	Ezintsha	Johannesburg
United Kingdom	Liverpool University Hospitals NHS Foundation Trust	Liverpool
United Kingdom	Kings College Hospital NHS Foundation Trust	London
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton

Sponsors (5)

Lead Sponsor	Collaborator
University of Liverpool	Liverpool School of Tropical Medicine, Liverpool University Hospitals NHS Foundation Trust, University of Cambridge, University of Southampton

Countries where clinical trial is conducted

South Africa,  United Kingdom, 

References & Publications (5)

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. — View Citation

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. — View Citation

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 — View Citation

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 — View Citation

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, Rowlan — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CST-8: Measure PK of nirmatrelvir and ritonavir in tears, saliva and nasal secretions	Concentration of nirmatrelvir and ritonavir in non-plasma	From randomisation to Day 5
Other	CST-8:To characterise genetic variability in SARS-CoV-2 before and during treatment via PCR analysis	PCR analysis re Baseline and treatment emergent genetic mutations in SARS-CoV-2	From randomisation to Day 11
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	Master Protocol: Safety assessed by rate of adverse events	Adverse event rate according to CTCAE v5	Up to 29 days from randomisation
Secondary	Master Protocol: To evaluate clinical improvement	Proportion of patients with clinical improvement (as defined above) at day 8, 15 and day 29.	From randomisation to day 29
Secondary	Master Protocol: To evaluate clinical improvement using WHO clinical progression scale	Change at day 8 and 15 from randomisation in the WHO Clinical Progression Scale	From randomisation to day 15
Secondary	Master Protocol: To evaluate clinical improvement using WHO clinical progression scale	Time to a one point change on the WHO Clinical Progression Scale	From randomisation to day 29
Secondary	Master Protocol: To evaluate clinical improvement using SpO2/FiO2	The ratio of the oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2)	From randomisation to day 29
Secondary	Master Protocol: To evaluate discharge	Proportion of patient discharged at days 8, 15 and 29	From randomisation to day 29
Secondary	Master Protocol: To evaluate admission to ICU	Admission rate to ICU	From randomisation to day 29
Secondary	Master Protocol: To evaluate safety further (WCC)	White cell count on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29	From randomisation to day 29
Secondary	Master Protocol: To evaluate safety further (Hg)	Haemoglobin on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29	From randomisation to day 29
Secondary	Master Protocol: To evaluate safety further (platelets)	Platelets on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29	From randomisation to day 29
Secondary	Master Protocol: To evaluate safety further (creatinine)	Creatinine on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29	From randomisation to day 29
Secondary	Master Protocol: To evaluate safety further (ALT)	ALT on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29	From randomisation to day 29
Secondary	Master Protocol: To evaluate overall mortality	Mortality at Days 8, 15 and 29. Time to death from randomisation	From randomisation to day 29
Secondary	Master Protocol: To evaluate the number of oxygen-free days	Duration (days) of oxygen use and oxygen-free days	From randomisation to day 29
Secondary	Master Protocol: To evaluate ventilator-free days	Duration (days) of mechanical ventilation and mechanical ventilation-free days	From randomisation to day 29
Secondary	Master Protocol: To evaluate incidence of new mechanical ventilation use	Incidence of new mechanical ventilation use	From randomisation to day 29
Secondary	Master Protocol: To evaluate National Early Warning Score (NEWS)2/qSOFA	NEWS2/qSOFA assessed daily while hospitalised	From randomisation to day 29
Secondary	Master Protocol: To evaluate translational outcomes (Viral Load)	Change in viral load over time	From randomisation to day 29
Secondary	Master Protocol: To evaluate translational outcomes (Baseline SARS-COV-2)	Change in viral load over time	From randomisation to day 29
Secondary	CST-2 Additional: Pharmacokinetic Objective: To define PK of EIDD-2801 and EIDD-1931 in plasma following multiple doses administered to patients with COVID-19.	Concentrations of EIDD-2801 and -1931 in plasma	Samples collected on Day 1 and Day 5 post-randomisation
Secondary	CST-2 Additional: Virologic Objective: To assess the difference in viral clearance (time to negative PCR) between EIDD-2801 and control.	Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nasal swab.	Swabs taken on Day 1 (day of randomisation), 3, 5, 8, 11, 15, 22 and 29
Secondary	CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (FLU-PRO)	Patient Reported Outcome Measures (FLU-PRO).	From randomisation to Day 29
Secondary	CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (WHO Scale).	WHO Progression Scale at day 15 and 29	From randomisation to Day 29
Secondary	CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (NEWS2)	NEWS2 (National Early Warning Score2) assessed during study clinic visit on days 15 and 29.	From randomisation to Day 29
Secondary	CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (mortality)	Mortality at Days 15 and 29	From randomisation to Day 29
Secondary	CST-2 Additional: Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients (death)	Time from randomisation to death	From randomisation to Day 29
Secondary	CST-6 Additional: To characterise the pharmacokinetics (PK) of multiple doses of IV Favipiravir	Plasma PK parameters of IV Favipiravir	From randomisation to Day 8
Secondary	CST-6 Additional: To investigate the ability of IV Favipiravir to reduce the duration of signs and symptoms of COVID-19 in-patients	WHO Progression Scale (WHO, 2020)	Randomisation to Day 15 and Day 29
Secondary	CST-6 Additional: To investigate the effect of IV Favipiravir on SARS-CoV-2 viral load	Viral load change from baseline over time	From randomisation to Day 29
Secondary	CST-8: Assess feasibility for late phase study by reviewing any recorded AEs and SAEs	Review of any adverse events	From randomisation to Day 29
Secondary	CST-8: Assess feasibility for late phase study by reviewing hospitalisation or death up to Day 29	Death and hospitalisation up to Day 29	From randomisation to Day 29
Secondary	CST-8: Measure concentrations of IMP re evidence of virological efficacy	PK concentrations of both IMPs and their circulating metabolites in plasma.	From randomisation to Day 11
Secondary	CST-8: Measure PK of each drug within the combination	PK concentrations of both IMPs and their circulating metabolites in plasma.	From randomisation to Day 11
Secondary	CST8: Review evidence of virological efficacy via viral elimination slopes	Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nose and throat swab	From baseline to Day 11
Secondary	CST8: Vital signs (Heart Rate) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11	Vital sign measure 1 heart rate (beats/min) - to be part of aggregated review of pt vitals to assess safety and tolerability.	From randomisation to Day 11
Secondary	CST-8: Vital signs (Blood Pressure) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11	Vital sign measure 2 Blood Pressure (mmHG) - to be part of aggregated review of pt vitals to assess safety and tolerability.	From randomisation to Day 11
Secondary	CST-8: Vital signs (Respiratory Rate) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11	Vital sign measure 3 respiratory rate (breaths/min) - to be part of aggregated review of pt vitals to assess safety and tolerability.	From randomisation to Day 11
Secondary	CST-8: Vital signs (Temperature) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11	Vital sign measure 4 temperature (degrees c) - to be part of aggregated review of pt vitals to assess safety and tolerability.	From randomisation to Day 11
Secondary	CST-8: Vital signs (Oxygen Saturation) at Screening, Baseline/Day 1, Day 3, Day 5 and Day 11	Vital sign measure 5 oxygen saturation (FiO2 as %) - to be part of aggregated review of pt vitals to assess safety and tolerability.	From randomisation to Day 11

External Links

•   The AGILE Clinical Trial Platform website