Cambridge University researchers will give increasing doses of peanut flour to 104 British children, up to the equivalent of five nuts a day.
Twenty out of 23 sufferers in an earlier study became able to eat more than 30 peanuts safely.
The new £1m three-year trial could lead to a widely available treatment.
About one in 50 young people in the UK suffers from peanut allergies which can cause breathing problems, itching and, in severe cases, a potentially fatal inflammatory reaction called anaphylaxis.
The new trial funded by the Department of Health's Institute of Health Research will involve more than 100 seven to 17-year-olds.
They will be given daily doses of peanut flour, starting at about one milligram, added to yoghurt.
"This is going to be the largest trial of its kind in the world and it should give us a definitive idea of whether the approach works and whether it's safe," said Dr Andrew Clark.
The pilot study built up sufferers' tolerance to five nuts, or 800 milligrams, which was then taken as a maintenance treatment for at least six weeks.
A year on from the start of the study, 20 of the patients could eat 32 peanuts safely - meaning they no longer needed to screen food labels and be wary of what they ate.
The researchers believe a treatment could be available within two to three years.
But they warned against people attempting their own trials at home.
