ECRAID-Base Launches European Clinical Research Alliance

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COMBACTE-MAGNET

Combatting bacterial resistance in Europe – Molecules against Gram-negative infections
COMBACTE-MAGNET focuses on the most vulnerable category of patients: those who are critically ill and being treated in intensive-care units. It aims to increase our understanding of the needs of these patients and doctors and use that knowledge to advance the development of well-targeted, life-saving treatments.

The consortium brings together researchers from four pharmaceutical companies, and over thirty leading academic medical centers from ten European countries.

COMBACTE-MAGNET aims to:

  • provide ground-breaking multinational phase I, II, and III studies targeting multidrug-resistant Gram-negative bacteria;
  • analyze data about current microbial threats, treatment and drug resistance patterns in European countries where ICU patients are most at risk;
  • gather information on biological markers of Pseudomonas aeruginosa infections;
  • create mathematical models of the infection’s effects;
  • provide a better understanding of why various patients may respond differently to infections;
  • provide researchers with knowledge to design more efficient and effective clinical trials of new molecules, accelerating the drug-development process enormously.

Analyzing data

The consortium will analyze data about current microbial threats, treatment and drug resistance patterns in European countries among at risk ICU patients. Research efforts include the assessment of biological markers of P. aeruginosa infections, the examination of the variability of immune response to these infections, and the development of mathematical models to estimate the disease burden of these infections and the impact of interventions to counter them. Such knowledge will enable researchers to design more efficient and effective clinical trials of new molecules.

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Network of epidemiological data and expertise

COMBACTE-MAGNET also contains one of the key pillars of the COMBACTE Consortium: EPI-Net

EPI-Net

EPI-Net is a European network that harmonizes and connects various European systems of disease surveillance, by linking clinical, microbiologic, and public health data. EPI-Net will complement the general COMBACTE-NET backbone by strengthening our ability to monitor the spread of healthcare-associated infections and antibiotic resistance across Europe.

Clinical trials

Within COMBACTE-MAGNET the following clinical studies are being/have been executed:

EVADE

A Phase II, randomized, placebocontrolled safety and efficacy trial of MEDI3902, a bispecific monoclonal antibody against P. aeruginosa PcrV and Psl, for the prevention of nosocomial pneumonia due to P. aeruginosa in adult ICU patients. MEDI3902 is being developed by AstraZeneca.

RESCUING

A retrospective observational study to assess the clinical management and treatment outcomes of hospitalized patients with complicated urinary tract infections, in countries with a high prevalence of multidrug resistant Gram-negative bacteria including Bulgaria, Greece, Hungary, Israel, Italy, Romania, Turkey, and Spain. Performed in collaboration with AiCuris.

AIC499

A new member of the family of so-called beta-lactam antibiotics with enhanced betalactamase stability and activity against Gram-negative pathogens, including P. aeruginosa and Acinetobacter spp. Alone, or in combination with a beta-lactamase inhibitor (BLI), AIC499 is active against a broad range of multidrug resistant isolates. AIC499 is being developed by AiCuris.

WP3A

Specimen analysis of the ASPIRE-ICU cohort participants to detect and characterize P. aeruginosa pneumonia. It will contribute to the assessment of host- and pathogen-related factors on ICU pneumonia and therefor further optimize patient selection for clinical trials.

WP3B

A mathematical modeling effort to develop an analytical framework and statistical tools to describe the burden of P. aeruginosa in European ICUs and determine the most impactful interventions.

Clinical trials for candidate drugs

COMBACTE-MAGNET performs pharmaceutical trials of two potential new treatments:
  • MEDI3902, a bispecific monoclonal antibody that inhibits two key virulence factors of Pseudomonas aeruginosa, PcrV and Psl. It has shown promising activity against P. aeruginosa in laboratory and animal studies, and has already undergone Phase I safety testing in adult humans. The consortium will carry out Phase II and Phase III studies in adult ICU patients to learn more about the antibody’s safety, its optimal dosing, and its efficacy in ICU patients;
  • AIC499, potentially a new and potent member of the family of beta-lactam antibiotics. Given alone or in combination with a beta-lactamase inhibiting drug (BLI), AIC499 has shown strong activity against a broad range of multidrug-resistant strains of P. aeruginosa and Acinetobacter, both in laboratory and animal studies. AIC499 is being developed by the German-based biotechnology firm AiCuris. COMBACTE-MAGNET carries out Phase I and Phase II trials to assess the safety and the efficacy of AIC499.
COMBACTE-MAGNET: Molecules against Gram-negative infections in intensive-care units 3

Management board members

From left to right: Dr. Hasan Jafri (AstraZeneca), Dr. Cuong Vuong (AiCuris), Prof. Alasdair MacGowan (University of Bristol), Prof. Dr. Marc Bonten (UMC Utrecht)

Project Management Office

From left to right: Dr. Ram Venkatachalam (UMC Utrecht), Claire-Marie Martis (UMC Utrecht), Elodie Pfender (CHU Limoges), Kristin Kopasz (AstraZeneca), Sally Grier (North Bristol NHS Trust), Dr. Ron de Winter (UMC Utrecht), Terramika Bellamy (AstraZeneca)

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