Agile CST-3

Title

Candidate Specific Trial-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

CST-3A is an open label single arm trial to assess the safety and tolerability of nitazoxanide in healthy volunteers.

Objectives

Primary:

Safety objective: To determine the safety, tolerability, optimum dose and dosing schedule of nitazoxanide in healthy subjects.

Secondary:

Pharmacokinetic objective: To define PK of tizoxanide, tizoxanide glucuronide and nitazoxanide (if detected) in plasma following multiple doses administered to healthy volunteers

Tertiary

Pharmacokinetic Objective: To define non-plasma PK of tizoxanide, tizoxanide glucuronide and nitazoxanide (if detected) following multiple doses administered to healthy volunteers

Trial design

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.

Safety and plasma PK Data on all twelve participants in each cohort will be reviewed by the Safety Review Committee for a decision of how to proceed. This will be assessed against the existing pre-clinical 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 is 1500mg twice daily. A further two cohorts of 12 participants may be recruited dependent on the safety and PK data from the previous cohort. 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 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.

Trial Status

Open to recruitment.

Population

Healthy volunteers

Senior Trial Manager:

Karen Martin

Trial Manager:

Izabela Eberhart

Trial Monitor:

Parys Hatchard

Trial Statistician:

Geoff Saunders