Within the current COVID-19 Public Health Emergency of International Concern, understanding the effectiveness of treatment strategies in patients with proven infection that focus on reduction of virus-induced clinical complications is urgently needed.
Patients with COVID-19 can present with pulmonary edema early in disease. We have proposed that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs, with this angioedema being kinin-dependent. We have already conducted a proof of concept study with B2R antagonist icatibant, providing evidence for the involvement of the kallikrein-kinin system. However, icatibant has some shortcomings.
Now, we hypothesize that targeting the kallikrein-kinin system by inhibiting plasma kallikrein with lanadelumab has the potential to prevent acute respiratory distress syndrome in patients hospitalized with symptomatic COVID-19. We will conduct a phase-2-study, pivotal for clinical development of lanadelumab for treatment of COVID-19. We will investigate whether intravenous lanadelumab can lower oxygen need and prevents resurgence of oxygen need during COVID-19 infection and is safe in COVID-19 patients. Moreover, we will study the effects of plasma kallikrein inhibition on immunological and kinin specific signatures and perform PK/PD of intravenous lanademulab in COVID-19 patients. Finally, we will provide a rationale and data on lanadelumab to implement this strategy in REMAP-CAP globally.
This study must be considered as an experimental domain for REMAP-CAP. If we deliver the proof of concept of lanadelumab, the applicants of this proposal can introduce the strategy in REMAP-CAP globally.