Wednesday, May 10, 2006

Injury to Research Volunteers -- The Clinical-Research Nightmare (The TGN1412 Trial)

From the NEJM:
At 8 a.m. on Monday, March 13, 2006, eight healthy young men entered a trial of a drug under development by the small German immunotherapeutics company TeGenero. Six of the volunteers were assigned to receive active drug, and two were to receive placebo. The trial was being conducted for TeGenero by Parexel, a large contract research organization, at its facility at Northwick Park Hospital outside London. The six volunteers were to be the first humans to receive TGN1412, a humanized monoclonal antibody designed as an agonist of the CD28 receptor on T lymphocytes, which stimulates the production and activation of T lymphocytes. It was hoped that this product would benefit patients with B-cell chronic lymphocytic leukemia or autoimmune diseases such as multiple sclerosis or rheumatoid arthritis. Preclinical testing, including tests in rabbits and monkeys that used doses up to 500 times as high as the doses received by the first group of volunteers, reportedly showed no signs of toxicity.

However, after receiving injections of TGN1412, the six volunteers became desperately ill, had multiple-organ failure, and were transferred to an intensive care unit2 with what has been described as a cytokine release syndrome. As of April 5, five of the volunteers had been discharged from the hospital, and the other man appeared to be recovering. This unexpected and devastating outcome is currently under investigation by the relevant authorities under the supervision of the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA), which originally approved the trial and its protocol. A preliminary report has now been completed and released. The serious injuries to these volunteers compel us to reassess the safety of such clinical trials in general, particularly those involving healthy volunteers.
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