Study Detail

AGILE: CST-2

CST-2: 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

Status: Open

Type: Interventional

Funder: Merck Sharp & Dohme Limited

Sponsor: University of Liverpool

CI: Saye Khoo

IRAS-Number: 282781

CPMS-ID: 49172

Approval Date: 17 March 2021

Summary:

This study is a parallel group, randomised controlled phase I/II Bayesian adaptive trial to assess the effect of EIDD-2801 versus control on time to viral clearance. Patients in phase I will be recruited in cohorts of minimum size six (randomised to treatment or control in 2:1 allocation ratio), with the phase I dose cohorts of six each assessed for safety. Dose-finding will be carried out as per the master protocol (section 4.2.1) with the following exceptions: • Safety will be reviewed 7 days after the first dose • No borrowing of control patients is anticipated due to the eligibility criteria for this treatment. Once a suitable dose has been identified, a 2-stage phase II study starts. In the first stage (Phase IIa) 60 patients are equally randomised between EIDD-2801 and placebo. If the probability of the hazard ratio between arms being greater than 1 (i.e., in favour of EIDD-2801) is more than 0.8, the study will stop for efficacy; if this probability is less than 0.3, then the study will stop for futility. Within this range, the trial will be expanded to stage 2 (Phase IIb) where an additional 120 patients are equally randomised between EIDD-2801 and placebo.

Study URL:

https://www.agiletrial.net/

Back to listing

AGILE: CST-3A

CST-3A: A Multicentre, Adaptive, Phase I trial to Determine the optimal dose, Safety and Efficacy of Nitazoxanide for the Treatment of COVID-19

Status: Closed

Type: Interventional

Funder: Unitaid

Sponsor: University of Liverpool

CI: Dr Lauren Walker

IRAS-Number: 282781

CPMS-ID: 49171

Approval Date: 17 March 2021

Summary:

This study is an open label single arm trial to assess the safety and tolerability of nitazoxanide in healthy volunteers. Participants in phase Ia will be recruited in cohorts of twelve participants with each cohort being assessed for safety and tolerability and pharmacokinetics. Data from a minimum of 12 participants is required for the PK analysis. The Trial Management Group (TMG) will review real time safety and DLT data during each cohort. Refer to CST-3A Safety Management Plan for the process of cross-site reporting of safety events as defined for participant withdrawal criteria (refer to section 7 of CST-3A protocol) or cohort stopping criteria (refer to section 6.10 of CST-3A protocol). There will be a formal Safety Review Committee (SRC) after twelve participants have completed each cohort, however the TMG can stop recruitment and initiate an SRC review at any point should there be any concerns with regard to participant safety. Safety and plasma PK Data on all twelve participants in each cohort will be reviewed by the SRC for a decision of how to proceed as specified in section 4.2. This will be assessed against the existing preclinical PBPK models to determine whether the optimal dose and regimen has been attained. Safety and tolerability will be reviewed 10 days after the first dose. The starting dose for nitazoxanide in this protocol will be 1500mg twice daily. A further two cohorts of 12 participants may be recruited dependent on the safety and PK data from the previous cohort (sections 4.2 and 6.11). A maximum of three cohorts of 12 participants will be dosed in CST-3A. Nitazoxanide dose level may be higher or lower in subsequent cohorts but will not exceed a total daily dose of 3500mg. In addition, a dose regimen where intolerable toxicity has been observed (defined by the stopping criteria in section 6.10) will not be repeated. Once a safe nitazoxanide dose and suitable regimen has been identified, no further healthy volunteer cohorts will be dosed and, instead, CST-3B (COVID-19 patients) will be opened. At least 12 participants on a given dose level or regimen are required for dose escalation or final recommendation

Study URL:

https://www.agiletrial.net/

Back to listing

AGILE: CST-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

Status: Open

Type: Interventional

Funder: GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LIMITED; VIR BIOTECHNOLOGY, INC.

Sponsor: University of Liverpool

CI: Dr Richard Fitzgerald

IRAS-Number: 282781

CPMS-ID: 49170

Approval Date: 17 March 2021

Summary:

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

Study URL:

https://www.agiletrial.net/

Back to listing