COMBACTE-MAGNET - Combatting Bacterial Resistance in Europe - Molecules against Gram Negative Infections
Zusammenfassung
Antimicrobial resistance (AMR) is a major global public health threat, and most troublesome is the rapid emergence and dissemination of multidrug resistant (MDR) Enterobacteriaceae, Acinetobacter species and Pseudomonas aeruginosa. There is an unmet medical need to prevent P. aeruginosa infection in critically ill patients and to develop new antibiotics for infections caused by Gram- negative bacteria (GNB). The Combatting Bacterial Resistance in Europe - Molecules against Gram-Negative Infections (COMBACTE-MAGNET) consortium will provide groundbreaking multinational phase 2 and phase 3 studies in adult intensive care unit (ICU) patients and a phase 1 paediatric safety and PK study with the bispecific immunoglobulin (IgG)1 mAb (MEDI3902) targeting the pathogenic components PsI and PcrV as a new approach for preventing P. aeruginosa infections, especially pulmonary infections, in ICU patients. In addition, the consortium will perform phase 1 and phase 2 studies, including extensive pharmacokinetic/pharmacodynamic (PK/PD) studies, with a new beta‐lactam ‐ AIC499 ‐ with enhanced beta‐lactamase stability and in vitro/ in vivo activities against MDR-GNB, including P. aeruginosa and Acinetobacter spp. Alone, or in combination with a beta‐lactamase inhibitor (BLI), AIC499 is active against MDR isolates producing a wide range of beta‐lactamases, and therefore, offers the real prospect of a new treatment option for patients with life-threatening infections due to MDR GNBs.
The COMBACTE-MAGNET consortium brings together 5 pharmaceutical industry partners and 36 academic partners, and is a true nexus of world class researchers from 10 European countries with expertise in (i) designing and executing observational and interventional studies related to antibiotic‐resistant bacteria; (ii) conducting high‐quality research in the epidemiology, prevention, and treatment of infections caused by MDR‐GNB, (iii) identifying novel biomarkers in critically ill patients; (iv) performing Phase I PK/PD studies; (v) performing Phase 2 studies enriched for PK/PD endpoints; and (vi) performance of large definitive Phase 3 randomized controlled trial (RCT) for regulatory purposes. The two European Federation of Pharmaceutical Industries and Associations (EFPIA) project sponsors, MedImmune and AiCuris, will provide all required study‐related expertise in clinical development of monoclonal antibodies and antibiotics with MEDI3902 and AIC499 plus BLI as Investigational Medicinal Products (IMPs), respectively. Key strengths of the COMBACTE-MAGNET consortium is its direct links to the ND4BB Topic 1 COMBACTE network (Clinical Trial Network [CLIN‐Net], Laboratory Trial and Research Network [LAB-Net], and Statistical Trial and Research Network [STAT‐net]), the ND4BB Topic 5 COMBACTE-CARE consortium, participation of the Paediatric European Network for the Treatment of AIDS and Infectious Diseases (PENTA-ID) network for pediatric infection studies, and the European Forum for Good Clinical Practice (EFGCP), a not‐for‐profit, Innovative Medicines Initiative (IMI)‐ and FP7‐funded, organization specialized in delivering tailor‐made, practice‐relevant Good Clinical Practice (GCP) training activities in European Union (EU) countries. The clinical studies related to MEDI3902 and of AIC499 will be supported by innovative epidemiological studies, including mathematical modeling of the consequences of P. aeruginosa infections. Furthermore, detailed biomarker studies will be performed to explore associations of host biomarkers (e.g., pre‐existing antibodies against P. aeruginosa virulence factors, protein biomarkers, and ribonucleic acid (RNA) molecules) and infections, disease severity and outcome, which will enhance the successful execution of clinical trials. Finally, COMBACTE-MAGNET will set up an unprecedented collaboration, called EPI-Net, to map and organize available surveillance systems in Europe in order to optimize surveillance of antibiotic resistance and healthcare associated infections. EPI-Net will engage representatives from major EU‐financed projects, stakeholders, experts, and industry to develop a consensus programme and homogenous approach on current and future epidemiologic surveillance strategies in Europe.