AGILE CST-6

Title

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

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 (IV) Favipiravir for the Treatment of COVID-19

Description

The first phase will be a 2:1 randomised open-label standard of care (SoC) controlled phase I of IV Favipiravir, followed by a 1:1 blinded, parallel group phase II trial of IV Favipiravir versus placebo (plus SoC)

Objectives

Primary Objectives:

Phase I:

• To determine the safety and tolerability of multiple doses of IV Favipiravir in patients with COVID-19
• To determine the maximum safe dose of IV Favipiravir for efficacy evaluation in phase II

Phase II:

• To investigate the efficacy of IV Favipiravir compared with placebo to reduce the SARS-CoV-2 viral load

Secondary Objectives:

Phase I:

• To characterise the plasma pharmacokinetics (PK) of multiple doses of IV Favipiravir
• To investigate the effect of IV Favipiravir on SARS-CoV-2 viral load
• To investigate the ability of IV Favipiravir to reduce the duration of signs and symptoms of COVID-19 in-patients.

Phase II:

• To determine the safety and tolerability of IV Favipiravir
• To characterise the plasma PK of IV Favipiravir
• To compare the effect of IV Favipiravir versus placebo on overall mortality, time to discharge, duration of oxygen use (and oxygen free days) and incidence and duration of new mechanical ventilation use
• To evaluate time to, and proportion of, clinical improvement (WHO clinical progression scale (WHO, 2020)).

Exploratory Objectives:

Phase I & II:

• To characterise the non-plasma PK of Favipiravir (saliva, tears, nasal secretions) and its active intracellular triphosphate in PBMC
• To investigate the exposure-response relationship of IV Favipiravir on SARS-Cov‑2 viral dynamics
• To characterise virus and host immune response
• Measure immune response by aldehyde oxidase (AO) / xanthine oxidase (XO) activity

Trial Design

The first phase will be a 2:1 randomised open-label standard of care (SoC) controlled phase I of IV Favipiravir, followed by a 1:1 blinded, parallel group phase II trial of IV Favipiravir versus placebo (plus SoC). A phase I will be carried out to test the safety and tolerability of IV Favipiravir in hospitalised patients.

Following review of safety, tolerability and PK data from evaluated phase I doses, an IV Favipiravir dose will be selected to progress to phase II. The selected dose of IV Favipiravir will be evaluated in a blinded, placebo controlled randomised phase II trial, which will assess the safety and virological efficacy.

Trial Status

Recruiting

Population

Adult in-patients (≥18 years) with laboratory confirmed COVID-19 infection by positive polymerase chain reaction (PCR) test.