Investigators to examine Northwick Park trial safety
pharmafile | March 16, 2006 | News story | Research and Development |
Two men involved in a UK clinical trial of new anti-inflammatory drug remain in a critical condition more than three days after falling ill.
Six volunteers received an injection of a new biological drug in a phase I trial at Northwick Park Hospital in North London, but were all admitted to intensive care within hours after suffering a severe reaction.
The condition of four of the men has now stabilised, but two remain critically ill, as questions mount about why the drug, called TGN 1412, proved to be so dangerous.
Details have emerged from other volunteers participating in the study, with some claiming all six men were given injections at the same time – something which best practice dictates should be avoided to minimise risk to patients.
Experts in the field remain unsure about exactly why the men suffered potentially fatal reactions to the drug, with life-threatening side-effects virtually unheard of in phase I trials.
Contamination of the drug and problems with its delivery or dosage are under suspicion, but the most likely explanation is that its effect differs significantly in humans compared to animals.
Myfanwy Marshall, the girlfriend of one of the critically ill men, told the BBC that animals had died in pre-clinical trials of the drug, and that doses for human trials had been reduced in response.
But TeGenero, the German company that discovered TGN 1412, has denied pre-clinical trials in animals had uncovered dangerous side effects.
"These events were completely unexpected and do not reflect the results we obtained from initial laboratory studies, which enabled us to progress investigations into human volunteers," said Dr. Benedikte Hatz, TeGenero's chief executive.
The trial is being conducted by Paraxel on behalf of TeGenero, and Dr. Hatz said the company had adhered to standard research guidelines.
TGN 1412 is a humanised agonistic anti-CD28 monoclonal antibody intended to treat autoimmune/inflammatory diseases such as rheumatoid arthritis and haemato-oncological malignancies such as leukaemia.
The UK medicines regulator the MHRA has sent inspectors to the medical research unit on the Northwick Park hospital campus to start its investigations, which MHRA chief executive, Prof. Kent Woods pledged would be 'exhaustive'.
The MHRA is collaborating with North West London Strategic Health Authority, Department of Health, and Metropolitan Police as part of the inquiry.
Related links
The incident has been covered extensively across the UK media, sparking debate about the overall safety of clinical trials.
The BBC and the Daily Mail are both inviting members of the public to join online debates about clinical trials, attracting a large number of respondents with varying opinions.
