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Agile CST-2

Title

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

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

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

Closed

Population

Adult out-patients (≥18 years) with laboratory-confirmed SARS-CoV-2 infection (PCR) who are within 5 days of symptom onset.

Trial Team

Senior Trial Manager:

Emma Knox

Trial Manager:

Calley Middleton

Contact Information

Email: [email protected]

SAE reporting: 

Email: [email protected]

All essential trial documentation for each CST are hosted on the main AGILE website.

Saye H Khoo, Richard Fitzgerald, Thomas Fletcher, Sean Ewings, et al: Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a phase 1, dose-escalating, randomised controlled study.  Journal of Antimicrobial Chemotherapy, Aug 2021, https://doi.org/10.1093/jac/dkab318

Press releases, video clips and other external websites

(The Agile Team cannot accept responsibility for external websites)

AGILE website (press section) – https://www.agiletrial.net/for-press/

AGILE CST-2 opens in Southampton – January 2020

AGILE CST-2 opening – October 2020

AGILE launch – June 2020