The treatment of novel coronavirus infections (COVID-19) is an important social issue. Although many of infected patients have no symptom or a mild disease, the disease can become severe, especially in the elderly and patients with underlying diseases, leading to severe pneumonia and acute respiratory distress syndrome (ARDS).
Although the number of patients has been decreasing due to the widespread use of vaccines and other medicines, there are still issues such as viral mutations, and the patients who develop pneumonia do not disappear. Therefore, there is a need for therapeutics that can prevent the disease from worsening at home, prevent hospitalized patients from becoming seriously ill, and reduce the sequelae. We are developing an oral medicine that can solve these medical issues. We hope to contribute not only to prolonging the lives of patients, but also to reducing the burden on the medical field and effectively utilizing medical resources.
Phase II investigator-initiated clinical trial was conducted at seven medical institutions in Japan to evaluate the efficacy and safety of PAI-1 inhibitor for COVID-19 pneumonia (funded by AMED’s “Research Program for Emerging and Re-emerging Infectious Diseases (4th round)”). The trial was conducted quickly and efficiently, with the first subject enrolled in October 2020 and with the study completed in March 2021. It is difficult to verify the efficacy because it was an open-label study. However, there were no serious adverse events that could be causally related to the study drug, and the safety of RS5614 was confirmed in COVID-19 infected patients.
In June 2021, we started a placebo-controlled blinded study in 100 patients with moderate pneumonia at 20 major medical institutions in Japan (funded by AMED’s “Research Program for Emerging and Re-emerging Infectious Diseases (5th round)”). If patient enrollment proceeded smoothly, the clinical trial was scheduled to end at the end of March 2022. However, from October to December 2021, the number of patients infected with the novel coronavirus declined sharply and the number of subjects decreased, so the number of patients enrolled also declined. Therefore, we reconsidered the planned number of patients to be enrolled in the clinical trial at each of the investigational sites, and also decided to extend the study period. Although the number of patients infected with novel coronaviruses has been increasing since January 2022 due to the sixth wave, the number of patients enrolled in this clinical trial has not increased significantly because there are few cases of moderate pneumonia despite the high infection rate of the Omicron strain.
In the U.S., a Phase II investigator-initiated clinical trial is being conducted at Northwestern University with a similar protocol. Due to the high severity of novel coronavirus infection in the U.S., it has been difficult to obtain subject consent for this study, in which placebo is administered as a comparison, and patient enrollment has been delayed. Therefore, we have decided to extend the clinical trial at Northwestern University and conduct it after confirming the results of the preceding Japanese clinical trial.
At Medeniyet University in the Republic of Turkey, we have completed the early phase II investigator-initiated clinical trial (open-label) to confirm safety of RS5614. A double-blind study was prepared in outpatients with novel coronavirus pneumonia. However, since there are few cases of severe disease with the current Omicron strain infection, it is difficult to conduct the study with the primary endpoint (hospitalization rate). Currently the eligible patients and clinical trial plan are being reconsidered.