Jo Revill, health editor
April 9, 2006
The consent form for test that left six men critically ill listed a side effect which can seriously harm the immune system
The drugs company behind the clinical trial that left six volunteers fighting for their lives was well aware that the previously untested drug might seriously damage the immune system.
The consent form the men were asked to sign, which has been obtained by The Observer, warned that a possible effect of the drug was 'cytokine release' - a massive immune reaction to a chemical as it triggers a uncontrollable response from antibodies. Cytokine release or cytokine storm, as it is also known, can be life-threatening, although the form does not spell that out.
It is not known whether the doctor heading the trial at Northwick Park Hospital in north London verbally highlighted the specific nature of the cytokine risk to the participants. The form simply says it could cause a 'hives-like' allergic reaction. The volunteers were struck down with symptoms within minutes of being injected with the drug.
A string of possible side effects are listed on the form, revealed for the first time in this newspaper. Volunteers must sign such a document before they are allowed to participate in a trial, to show they understand the potential risks and so that the company is legally protected.
In the 12-page document prepared by Parexel, which carried out the trial on behalf of German biotech firm TeGenero, the potential side effects are listed. It states: 'As this is only the first time this drug will be given to man, this study may involve risks currently unforeseen.'
It adds: 'It is possible that you will not experience any side effects at allas the doses used in early human studies are always very small, and increased only ... but the following unintended effects may theoretically be encountered during any trial with a monoclonal antibody drug, though they did not occur even at the highest tested doses in animals.'
It lists the possible side effects as 'immunosuppression [increasing susceptibility to infection], autoimmunity [antibodies made by your own body against the drug], cytokine release [causing a hives-like allergic reaction] or anaphylaxis [a generalised allergic reaction that can be life-threatening].'
It emerged this weekend that the Medicines and Healthcare Products Regulatory Agency (MHRA) which authorised the trial was notified beforehand that there was this risk of cytokine release. TeGenero did tell the agency of a previous incident involving a similar drug which had provoked a serious adverse reaction in human volunteers.
One of the six men, Ryan Wilson, is still in hospital.
TeGenero said: 'The preliminary findings of the investigation of the UK authorities confirmed the highest standards were observed in developing TGN1412. There was no sign of risk from the extensive preclinical testing and we could not predict the serious reactions. The study obtained approval from German and UK authorities.'