Biomedical Catalyst – Use of Ovine Polyclonal Antibodies to Treat Severe Clostridium difficile Infections

One of the commonest causes of hospital acquired infection is the bacterium Clostridium difficile which causes diarrhoea and other effects by releasing two powerful toxins. Such infections far outnumber those due to MRSA and the Centre for Disease Control and Prevention in the USA has noted “...the incidence of deaths from C.difficile is greater than the extent of deaths from all the other intestinal diseases combined.” The present project involves a novel means of treating patients with severe C. difficile infections by injecting specific antibodies which bind to, and neutralise the toxins. The antibodies are produced by immunising sheep with miniscule amounts of inactivated toxins (similar to the vaccination of infants) and the antibodies are separated from other blood constituents, purified and filled into ampoules ready for intravenous administration as an adjunct to antibiotic therapy.

During the first eighteen months of the project a detailed investigational protocol will be prepared with guidance from Professor Mark Wilcox. As noted earlier, the incidence of CDI in the UK is falling due to measures such as improved hygiene and antibiotic stewardship. Furthermore, we believe that PolyCAb is most likely to offer patient benefit in the more serious forms of CDI. Typically, phase 3 registration studies of new CDI treatment drugs recruit only a minority of cases with severe CDI; in recent phase 3 studies of fidaxomicin about one third of cases were classified as having severe CDI.
Thus, it is intended to recruit 5-10 centres in the UK to identify approximately 40 patients suitable for a phase 2a clinical trial.
Professor Wilcox has already identified a potential network of UK sites that are interested in and have capacity to perform clinical trails of new antimicrobial agents (as part of a European clinical trials network initiative). We envisage that by recruiting suitable centres with clinical trial capability such a study can be fully completed in 24 months.
The patients will be aged 65 years or over with a proven diagnosis of severe CDI, which is usually defined according to systemic criteria, including white blood cell count (WCC) and serum creatinine increases. The study will be restricted initially to the minority of patients with the most serious forms of CDI. Inclusion/exclusion criteria will be designed to target those individuals in whom the chance of CDI complications is highest. All patients will receive, in addition to PolyCAb, the best possible standard of care such as vancomycin or fidaxomicin together with rehydration and other supportive measures. We envisage that ethical approval for such a study should be obtainable, noting that note that CDI treatment guidelines current list intravenous (pooled) immunoglobulin as a possible treatment option in very severe infection.
Study design Allocation: Non-randomized
Endpoint classification: Safety/Efficacy study
Masking: Open label