Initial translational analysis, EXPLORE, showed overexpression of C5a/C5aR pathway in patients with severe COVID-19
Innate Pharma SA today announced that the first patient was dosed in a randomized, doubleblind Phase II clinical trial, evaluating the safety and efficacy of its anti-C5aR antibody, avdoralimab (IPH5401), in COVID-19 patients with severe pneumonia.
The primary objective of this investigator-sponsored trial, named FORCE, is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by acute respiratory distress syndrome (ARDS).
The Phase II trial is supported by an exploratory translational study, EXPLORE COVID-19, which suggests that patients who progress towards severe COVID-19 disease exhibit an activation of the C5a/C5aR pathway.
“Through the translational data analysis in COVID-19 patients, we observed high levels ofcirculating C5a and over-activation of the C5a-dependent myeloid cell pathway, which isbelieved to contribute to inflammation in the lungs. Avdoralimab is a monoclonal antibody thatblocks C5aR and has the potential to reduce the inflammatory response in the lungs,” said Pr. Eric Vivier, PhD, Chief Scientific Officer at Innate Pharma and Professor at AP-HM (Marseille Public University Hospitals), Aix-Marseille University and Centre d’Immunologie de Marseille-Luminy, CNRS, Inserm and AMU. “In this randomized trial, we hope to demonstrate that the use of avdoralimab helps improve the prognosis of COVID-19 patients with severe pneumonia.”
“The intensive care units are currently overburdened in France, along with every country
affected by the pandemic. Hospitalization in intensive care units is often long, from 14 to 21 days, and physicians have no effective treatments for patients. The objective of this study is to investigate whether avdoralimab can reduce the duration of hospitalization, and the duration and need for mechanical ventilation in an important proportion of COVID-19 patients,” explains Pr. Nicolas Schleinitz, MD, Internal Medicine Service, Timone Hospital, Professor at AP-HM, Aix-Marseille University and Principal Investigator for the FORCE study.
About the clinical trial:
FORCE is a multi-center, randomized, double-blind, placebo-controlled Phase II trial evaluating avdoralimab in COVID-19 patients with severe pneumonia. The trial will be conducted in La Timone Hospital and Nord Hospital in Marseille (Hopitaux Universitaires de Marseille – AP-HM) and in the Hospital Laveran (HIA-Laveran).
The trial is expected to enroll a total of 108 patients (age 18-80) between two cohorts: one cohort of COVID-19 patients with severe pneumonia without acute respiratory distress syndrome (ARDS) at baseline and one cohort of COVID-19 patients with severe pneumonia complicated by ARDS and admitted in ICU at baseline. In each cohort, patients will receive avdoralimab or placebo.
Avdoralimab (IPH5401) in cancer:
Avdoralimab is a therapeutic antibody that specifically binds and blocks C5a receptors (C5aR) expressed on myeloid cells, including monocytes, macrophages and neutrophils. It is currently in Phase I development in solid tumors, including hepatocellular carcinoma and non-small cell lung cancer.
Avdoralimab in COVID-19:
C5a has been implicated in the pathogenesis of ARDS by promoting a proinflammatory environment, through the attraction of neutrophils and stimulation of immune cells such as T and B cells to release cytokines. Avdoralimab blocks C5aR and has the potential to reduce the inflammatory response in the lungs.
Pr Eric VIVIER