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The University of Southampton
Southampton Clinical Trials Unit

Agile CST-2

Title

Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment

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

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 ACCORD-2 (or RECOVERY) platform trials for further evaluation in the phase II/III setting.

Each candidate will be evaluated in its own trial (‘Candidate-Specific Trial (CST)), 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.

An AGILE Scientific Advisory Board will evaluate and prioritise candidate agents for inclusion in the study. Candidate-specific trial (CST) protocols will outline full details of each candidate trial.

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.

Objectives

Primary Objectives

Safety Objective: To determine the safety and tolerability of multiple ascending doses of EIDD-2801.
Efficacy Objective: To determine the ability of EIDD-2801 to reduce serious complications of COVID-19 including hospitalization, reduction in SaO2<92%, or death.

Secondary Objectives

Pharmacokinetic (PK) Objective: To define PK of EIDD-2801 and EIDD-1931 in plasma following multiple doses administered to patients with COVID-19.
Virologic Objective: To assess the difference in viral clearance (time to negative PCR) between EIDD-2801 and control.
Clinical Objective: To determine the ability of EIDD-2801 to reduce the duration of signs and symptoms of COVID-19 in patients based on a patient reported outcome tool.

Tertiary Objectives

Pharmacokinetic (PK) Objective: To define non-plasma PK of EIDD- 2801 and EIDD-1931 following multiple doses administered to patients with COVID-19 through samples of saliva, tears, dried blood spots and nasal swabs.
Pharmacodynamic (PD) Objective: To characterise virus and host immune response through samples of serum and nose/throat swab.

Trial Design

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 ACCORD-2 (or RECOVERY) platform trials 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 (minimum) 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort.

 

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. 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.

Trial Status

Open to recruitment.

Population

Adult out-patients with laboratory confirmed COVID-19 who are within 5 days of symptom onset. Patients aged ≥60 or ≥50 years of age with at least one underlying 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).

Phase I: Variable depending on dose escalation decisions, patients will be recruited in cohorts of 6 patients.

Phase II: A maximum of 180 participants, with efficacy review after 60.

 

 

 

 

 

Trial Team:

Senior Trial Manager:

Ellice Marwood (023 8120 5608)          

Trial Manager:

Nicky Downs (023 8120 5302)

Clinical Data Coordinator:

Lucy Johnson (023 8021 5605)

Contact Information

Email: agile2@soton.ac.uk

Fax: 0844 7740 621

SAE reporting:  ctu@soton.ac.uk or 0844 7740 621

 

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