Clinical Trial
This article was originally published in SRA
Executive Summary
All subjects in UK clinical trial suffer severe adverse reactions
All subjects in UK clinical trial suffer severe adverse reactions
A Phase I clinical trial in the UK has been stopped by the Medicines and Healthcare products Regulatory Agency (MHRA) after all six men who received a new monoclonal antibody drug were admitted to intensive care suffering from severe adverse reactions.
Eight volunteers took part in the trial which marked the first time this drug was tested in humans1. On 13 March 2006, six were given the drug and two others received placebo. Within hours, the six who had taken the drug started to experience severe adverse reactions and were admitted to the intensive care unit at Northwick Park Hospital, where the drug was being tested at an independent facility. This is run by the pharmaceutical services specialist, Parexel, which is conducting trials on the drug, TGN 1412, for the German biotech company, TeGenero2.
The MHRA has begun an investigation into what went wrong with the trial3. A spokesman for the agency said that although it is too early to say what caused the extreme reactions, it is investigating whether there was a flaw in the manufacturing process, the patients were accidentally given the wrong doses, or are reacting to an unforeseen biological effect. He said the investigation would likely take weeks to complete.
The drug had been authorised for Phase I trials by the MHRA and an independent ethics committee. Before Phase I trials can begin, the drug manufacturer has to apply for a licence to the agency and provide safety data on the product from laboratory and animal testing, as well as how it should be administered and the likely effect it will have in humans. The MHRA conducts a scientific review of the data supplied before authorising a “first time in man” clinical trial.
TeGenero said it was shocked at the reaction the drug had in the volunteers4. “These events were completely unexpected and do not reflect the results we obtained from initial laboratory studies,” said its chief executive officer, Dr Benedikte Hatz, in a statement.
TGN 1412 has been developed to treat leukaemia, rheumatoid arthritis and multiple sclerosis5. The company holds orphan drug designation from the European Medicines Agency (EMEA) for the drug to treat B-cell chronic lymphocytic leukaemia.
As RAJ went to press, it was reported that two of the volunteers had been allowed to go home having made an “excellent recovery”6. One man remains critically ill but has made improvements. The other three have left critical care but are continuing to receive specialist care.
References
1. MHRA press release, 14 March 2006, www.mhra.gov.uk
2. Parexel press release, 15 March 2006, www.parexel.com/news_and_events/press_releasesSingle.asp?id=233
3. Personal communication, MHRA, 16 March 2006
4. Press release, TeGenero, 15 March 2006, www.tegenero.com/news/statement_re_tgn1412/index.php
5. Public summary of positive opinion for orphan designation, EMEA, 1 July 2005, www.emea.eu.int/pdfs/human/comp/opinion/8595805en.pdf
6. Northwick Park Hospital press release, 29 March 2006, www.nwlh.nhs.uk/news/item.cfm?id=97