BMBF is supporting the trial
Vaccination and mass testing are the most important tools in tackling the COVID-19 pandemic. In addition, safe and effective drugs are needed to treat those who become sick. It is against this backdrop that the German Federal Ministry of Education and Research (BMBF) is funding research into drugs against COVID-19 and thus also the cooperation between the BIH at Charité, Bayer AG, the Leipzig and Würzburg university medical centers, and the consortium partner Unfallkrankenhaus Berlin. Funding of around 3.5 million euros has been made available to clinically test the COVID-19 substance as part of the CATCOVID trial.
The immune system plays a key role
Roland Eils, founding director of the BIH Digital Health Center, and Irina Lehmann, BIH Professor for Environmental Epigenetics and Lung Research, together with colleagues from Charité – Universitätsmedizin Berlin and University of Leipzig Medical Center, discovered that the immune system plays a crucial role in severe progression of COVID-19. “Using single cell analyses, we found out that epithelial cells infected by the virus send a ‘distress call’ to the immune system,” says Eils. “However, the immune cells that migrate in response to viral infection occasionally overshoot the target and with their exaggerated reaction, sometimes do more damage than the virus itself. So it was clear to us that any therapy would have to address the immune system’s role.”
Signaling molecules of the immune system, known as chemokines, are involved in the migration of immune cells into the airways. Epithelial cells and activated immune cells release chemokines and thus attract further immune cells. The immune cells have chemokine receptors on their surface with which they can “receive” the calls for help. “In our studies with single cell analyses we saw that one of these receptors in particular – chemokine receptor 1 (CCR1) – was associated with an augmented immune response and severe COVID-19 disease progression,” reports Lehmann. “So we had the idea to block this receptor in order to dampen the immune response.”
Bayer AG provides therapeutic agent
The scientists led by Eils and Lehmann therefore starting searching for known blockers of this receptor – and found one at Bayer. “We had developed a substance that was supposed to reduce chronic inflammation in pathologies such as autoimmune diseases,” reports Philip Larsen, Global Head of Research and Early Development at Bayer. “The CCR1 receptor also plays a role there. It might be helpful in the case of COVID-19, where an acute augmented immune response needs to be toned down. That is exactly what we now want to test with colleagues at the BIH.”
Strong network of partners
The clinical trial is managed at the BIH, with support provided by HiGHmed e.V. in Heidelberg. In addition to Charité – Universitätsmedizin Berlin, participating clinical trial sites include University of Leipzig Medical Center, the University Hospital of Würzburg and the Unfallkrankenhaus Berlin. Based on safety and tolerability data obtained from the phase I trial, the scientists can start right away with phase II to assess the efficacy of the substance. This provides a big head start in terms of time. “Bayer had already begun producing the pharmaceutical formulation at the beginning of the year, so that after just a few months we were able to start with patient enrollment,” says Eils.
University of Leipzig Medical Center has successfully enrolled the first patient. Dr. Sven Laudi, senior physician for intensive care medicine and lead physician for the trial, commented: “The current fourth wave of the pandemic shows us that despite the possibility of being vaccinated, drugs are also necessary that can directly influence disease progression. If the CCR-1 inhibitor is effective, its administration could prevent severe courses of COVID-19 and thus significantly reduce the frequency of COVID-19 patients being admitted to ICU. This would eliminate much of the threat from the disease, both from the perspective of the individual patient and from the perspective of the health care system as a whole.”
Meanwhile, final preparations are underway at the three other clinical trial sites to launch the trial. The aim is to enroll the required number of 208 evaluable patients in the current pandemic wave by promptly starting recruitment at Charité – Universitätsmedizin Berlin, the Unfallkrankenhaus Berlin and the University Hospital of Würzburg.
Publications in the journal Nature on the scientific basis of the clinical trial:
https://www.nature.com/articles/s41587-020-0602-4
https://www.nature.com/articles/s41587-020-00796-1
https://www.nature.com/articles/s41587-021-01037-9
Preliminary studies at the BIH:
The dangerous dual role of the immune system in COVID-19