AGILE CST-5

Title

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

Candidate-Specific Trial 5 (CST-5): A 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

Description

Phase I of this study will comprise a first-time-in-human dose-escalation phase for VIR-7832 in which subjects will be randomized to VIR-7832 or placebo in a 3:1 allocation ratio.

Each of these cohorts will be double-blind and blinded safety data will be reviewed between cohorts by a Safety Review Committee (SRC). Once a suitable dose is identified, VIR-7832 will progress to phase II, which will examine VIR-7832, VIR-7831 and placebo in a 2:2:1 ratio. The primary aim of this study is to assess the safety, tolerability and virological efficacy of VIR-7832 compared with placebo.

Objectives

Primary Objectives

Phase I:

∙ To determine the safety and tolerability of single doses of VIR-7832, to aid dose selection for Phase II

Phase II:

∙ To investigate the effect of VIR-7832 compared with placebo on SARS-CoV-2 viral load

Secondary Objectives

Phase I:

∙ To characterise the Pharmacokinetics (PK) of single doses of VIR-7832

Phase II:

∙ Safety Objective: To determine the safety and tolerability of single doses of VIR-7832 and VIR-7831

∙ To characterise the PK of single doses of VIR-7832 and VIR-7831

∙ To investigate the effect of VIR-7832 and VIR-7831, both compared with placebo, on SARS-CoV-2 viral load over time

∙ Clinical Objective: To evaluate time to, and proportion of patients with clinical improvement

Exploratory Objectives

Phase I:

∙ To investigate the exposure-response relationship of the VIR-7832-mediated effect on SARS-Cov-2 viral dynamics

Phase II:

∙ To compare the effect of VIR-7832 versus VIR-7831 on T-cell responses to SARS-CoV-2

∙ To investigate the clinical efficacy of VIR-7832

∙ To monitor for SARS-CoV-2 resistance mutations against VIR-7831 and VIR-7832

∙ To evaluate the effect of VIR-7832 and VIR-7831 versus placebo on potential biomarkers of host response to SARS-CoV-2

Trial Design

3:1 randomised, blinded, placebo-controlled phase I of VIR-7832, followed by a 2:2:1 blinded, parallel group Phase II trial of VIR-7832 versus VIR-7831 versus placebo. A phase I will be carried out to test the safety and tolerability of VIR-7832 in this group. Following review of safety and tolerability data from evaluated doses of VIR-7832, a dose (of up to 500 mg) will be selected to progress to phase II. The selected dose of VIR-7832 will be further evaluated in a blinded, placebo -controlled randomised Phase II trial, which will assess the safety and virological efficacy of VIR-7832 and VIR-7831

Trial Status

Closed to recruitment. In follow-up.

Population

Adult out-patients (≥18 years and ≤65 years in Phase I; ≥18 years in Phase II) with laboratory confirmed COVID-19 infection by positive polymerase chain reaction (PCR) test

Group B (mild-moderate disease) – as defined by master protocol

∙ Ambulant patients with peripheral capillary oxygen saturation (SpO2) >94% room air (RA), who have experienced symptoms of COVID-19 for <168 h (7 days)

Phase I: Variable, depending on dose escalation decisions, patients will be recruited into 3 cohorts of 8 patients.

Phase II: A maximum of 125 participants.