AGILE CST-8

Title

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

Candidate-Specific Trial 8 (CST-8): A Randomized, Multicentre, Seamless, Adaptive, Phase I Platform Study to Determine the Recommended Phase II dose and Evaluate the Safety and Efficacy of combination of Molnupiravir and Paxlovid® for the Treatment of COVID-19.

Description

This study is an open-label, randomised, Phase I dose de-escalation trial to assess the safety and tolerability of drug combination of molnupiravir and Paxlovid® on SARS-CoV-2.

Objectives

Primary Objectives:

• To determine the safety and tolerability of dose combinations of molnupiravir and Paxlovid®

Secondary Objectives:

• Establish feasibility for the combination to be trialed in a larger late phase platform
• To evaluate preliminary evidence of virological efficacy
• To characterise the pharmacology of each drug within the combination

Exploratory Objectives:

• To characterise pharmacology of Paxlovid® (i.e.nirmatrelvir and ritonavir) in tears, saliva and nasal secretions
• To characterise genetic variability in SARS-CoV-2 before and during treatment
• To evaluate changes in culturable virus on treatment

Trial Design

Open-label 2:1 randomised controlled Phase I de-escalation study of molnupiravir + Paxlovid® versus standard of care alone.

Phase I will be open label assessing de-escalating doses of molnupiravir with a fixed dose of Paxlovid® compared with Standard of Care (SoC). Patients in phase I will be recruited in cohorts of 6 (randomised to molnupiravir + Paxlovid®: SoC in 2:1 allocation ratio), with review of safety and tolerability between cohorts.

Trial Status

In set-up

Population

Adult out-patients (≥18 years) with laboratory confirmed COVID-19, who are within 5 days of symptom onset