Completed Infection & Immunity Lungs & Breathing

Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLAT-COV)

In plain English

AI plain-English summary

A clinical trial is testing whether cheap, existing drugs—including an anti-parasitic, an HIV medication, and a common blood thinner—can speed up how quickly the body clears the COVID-19 virus from the throat. The problem is that early in the pandemic, many repurposed drugs were rushed into large trials without knowing whether they actually suppressed the virus. This study, called PLAT-COV, directly measures viral clearance rates from serial throat swabs in low-risk adults with early, uncomplicated COVID-19. It uses an adaptive platform design that can rapidly reject ineffective drugs—those with less than a 10% probability of accelerating clearance—and flag promising ones with over 90% probability. The trial runs across three continents and includes a positive control (monoclonal antibodies or peginterferon-lambda) to validate the method. If successful, this platform will give researchers a fast, quantitative way to screen existing drugs for antiviral activity before committing to expensive phase 3 trials. It could also be adapted to test new antivirals against future respiratory viruses. The immediate impact is on clinical trial efficiency: instead of guessing which drugs work, funders and regulators will have hard pharmacometric data on viral clearance within weeks.

View original technical description
We propose to set up and validate a pharmacometric platform to provide quantitative assessment of antiviral effects in low risk adult patients with recent onset uncomplicated COVID-19 and high viral burdens. This assessment is based on measurement of oropharyngeal viral clearance rates. This will be a randomised, open label, group sequential adaptive platform trial to quantitate the antiviral activity of currently available potential (i.e. repurposed) treatments in low-risk adult patients with early COVID-19, through adjusted qPCR of serial oropharyngeal samples. It will be a mainly outpatient study conducted in three locations; one each in the Americas, Europe and Asia. The interventions to be evaluated in this first phase are hydroxychloroquine, lopinavir/ritonavir, ivermectin, miglustat, remdesivir, intranasal heparin, with the Regeneron monoclonal antibody cocktail or Peginterferon-lambda as a "positive control". This will identify drugs with a >90% probability of accelerating virus clearance compared to no treatment and will reject drugs with <10% corresponding probability. Drugs identified as accelerating viral clearance will undergo a further nested pharmacometric evaluation to characterise exposure–response relationships and inform dosing. This study will provide a platform for choosing antiviral drugs for phase 3 clinical trials. Once validated the platform can be used to evaluate new antivirals.

View the original record at the funder ↗

Researchers

Adrianus (Arjen) Dondorp (EPMC Awardee)Cintia Cruz (EPMC Awardee)James Callery (EPMC Awardee)James Watson (EPMC Awardee)Nicholas Day (EPMC Awardee)Nicholas White (EPMC Awardee)William Schilling (EPMC Awardee)

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Original classification

Therapeutics Accelerator

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