Nathalie Seigneuret (IHI Scientific Project Manager for COMBACTE), Lisa Grimsditch (EFPIA Partner, Pfizer, Project Management Office Lead COMBACTE-CARE), and Rienk Pypstra (EFPIA Partner, Pfizer, Project Management Office Lead COMBACTE-CARE) comment on the COMBACTE-CARE project.
Nathalie Seigneuret, IHI Scientific Project Manager for COMBACTE: “COMBACTE-CARE was set up to address a specific challenge: infections with carbapenem-resistant Gram-negative bacteria, which are often resistant to most other antibiotics as well. The project was designed to lay the groundwork for multicentre trials of new compounds that can help counter that challenge. With the project in its final stages, we can conclude that the consortium has delivered on its main objectives.”
“First and foremost, the EURECA study has generated, gathered, and analysed large amounts of observational clinical and epidemiological data on risk factors for serious carbapenemresistant Enterobacterales (CRE) infections and determinants of outcomes for the currently available treatment options” Nathalie says. “The results have provided us with important new insights. It has also informed the design of future randomised trials testing candidate CRE-fighting drugs. For example, how important it is to recruit patients from diverse populations. It has built a framework that helps us select the right study sites and find the right investigators, which helps to quickly maximise and optimise the sample of patients that are recruited into the trial. And it demonstrated the added value of setting up an innovative 24/7 support line because trials like these generally involve clinically complex patient populations.”
“COMBACTE-CARE has demonstrated how well a public-private partnership can work. There was a great sense of community in COMBACTE-CARE generally, and frequent communication ensured that everyone was up to date.”
Nathalie adds: “Using those and other important lessons, COMBACTE-CARE completed a Phase II study (REJUVENATE) ahead of schedule and also completed patient recruitment for a Phase III study (REVISIT), the final results of which will hopefully be announced soon.
Together, these studies evaluate the efficacy and the safety of aztreonamavibactam (also called ATM-AVI) for the treatment of serious infections with Gram-negative bacteria, including metallo-β-lactamase producing multidrug-resistant pathogens. Completing recruitment in Phase III was all the more impressive because of the added challenges posed by the sudden outbreak of the COVID-19 pandemic. Like in some other COMBACTE-related trials, recruitment of patients advanced less swiftly than was anticipated beforehand because the pandemic siphoned off availability, possibilities and priorities of investigators, hospital staff and other infectious disease experts.
This feat can be seen as a testament to the efficient collaboration between investigators from a pharma company, academic institutions, and a contract research organisation (CRO). Together, they were able to take effective measures that helped increase patient recruitment and managed to keep the study mostly on track.”
“The close collaboration between pharma, academia, and clinical research organisations managed to counter disruptions caused by the COVID-19 pandemic. Their experiences and this model of collaboration offer critical lessons for the design and execution of future trials.”Nathalie Seigneuret (IHI)
Rienk Pypstra, Pfizer and Project Management Office Lead COMBACTE-CARE: “The close collaboration between Pfizer and the COMBACTE-CARE team was key for selecting the best study sites for this Phase III trial. Pfizer helped select qualified investigators and a diverse population of patients from world regions with high CRE infection rates, while COMBACTE-CARE provided a global footprint and vast experience of infectious disease experts.”
Nathalie concludes: “Now, we all look forward to learning about REVISIT’s outcomes. Hopefully, they will show robust benefits of ATM-AVI, which could support an application for marketing authorisation in Europe. That in turn could add a treatment option for patients with serious Gram-negative bacterial infections, for whom at present such options are limited or non-existent. In all, COMBACTE-CARE has delivered on its promise to make important progress towards developing this and future new options for the benefit of patients at high risk.”
“COMBACTE-CARE has made an invaluable contribution by integrating knowledge and capabilities of industry and leading clinical and microbiology academic research groups from across Europe to meet challenges of crucial observational and interventional clinical studies.”