More than 3,000 people in the UK have caught the monkeypox virus in recent months, with more cases anticipated.
The virus, which is spreading rapidly in other countries as well, has been declared a global health emergency.
The infection typically gets better on its own, but recovery can take weeks and there can be serious complications.
"The aim is to find a treatment that can help people get better quicker and get out of quarantine," said Professor Sir Peter Horby, one of the PLATINUM trial researchers at the University of Oxford.
Around 500 patients will take part in the trial. Some will be treated twice-daily with tecovirimat tablets while they recuperate from the virus in their own home; others will receive a placebo - or dummy treatment - instead.
By comparing the two groups of volunteers, the researchers hope to have the results for the drug trial within months.
Tecovirimat - also known as Tpoxx - prevents the virus from leaving infected cells, stopping its spread within the body. It was licensed earlier this year for monkeypox, based on promising results from initial studies in animals and evidence of safety in healthy human volunteers.