In an effort to expedite research for agents with potential activity against symptoms associated with the novel coronavirus (COVID-19), the U.S. Food and Drug Administration (FDA) is evaluating and/or has approved a number of randomized clinical trials seeking to determine whether a drug has activity in this disease setting. Two of these studies are reported here.
Tocilizumab Study, COVACTA, Approved
The FDA has approved a randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the safety and efficacy of intravenous tocilizumab, an immunosuppressive agent, plus standard of care in hospitalized adult patients with pneumonia related to COVID-19, according to Genentech, the agent’s developer.
The clinical trial, called COVACTA, is being conducted in collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to evaluate tocilizumab combined with standard of care vs placebo plus standard of care.
The manufacturer has also indicated that they will provide 10,000 vials of tocilizumab to the U.S. Strategic National Stockpile for future use at the direction of the U.S. Department of Health and Human Services to further support the COVID-19 response efforts.
Enrollment is anticipated to start as early as April 2020, with a target accrual of 330 patients across the United States and other countries.
The primary and secondary endpoints of the phase III study include clinical status, mortality, mechanical ventilation, and intensive care unit (ICU) variables. Researchers will follow patients for 60 days postrandomization, and an interim analysis will be conducted to look for early evidence of efficacy.
Several independent clinical trials have already begun globally to evaluate the efficacy and safety of tocilizumab for the treatment of patients with COVID-19 pneumonia. However, there are still no well-controlled studies and limited published evidence on the safety or efficacy of tocilizumab in the treatment of patients with COVID-19. Currently, tocilizumab is not approved by the FDA for use in COVID-19 patients.
Tocilizumab is associated with serious adverse reactions, including infection leading to death in some patients, gastric perforation, and hepatotoxicity. Common side effects observed in patients treated with tocilizumab include upper respiratory tract infections, headache, hypertension, and injection-site reactions.
Tocilizumab is already approved by the FDA for the treatment of severe or life-threatening cytokine-release syndrome caused by chimeric antigen receptor T-cell therapy. Additionally, tocilizumab also has FDA-approved indications for rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systematic juvenile idiopathic arthritis.
Ruxolitinib Study, RUXCOVID, Planned
On April 2, 2020, Incyte announced that the company is working with the FDA to initiate a phase III clinical trial (RUXCOVID) to evaluate the efficacy and safety of the Janus kinase inhibitor ruxolitinib plus standard of care compared to standard-of-care therapy alone in patients with COVID-19–associated cytokine storm.
Because many patients with severe respiratory disease (eg, pneumonia) due to COVID-19 have features consistent with cytokine storm and increased activation of the JAK-STAT pathway, it is hypothesized that ruxolitinib may be able to play a role in treating these patients.
Additionally, given the urgent nature of the COVID-19 pandemic, Incyte intends to initiate a separate open-label emergency Expanded Access Program in the United States. The protocol will allow eligible patients with severe COVID-19–associated cytokine storm to receive ruxolitinib while it is being investigated for this indication.
Ruxolitinib is currently approved by the FDA for treatment of polycythemia vera in adults who have had an inadequate response to or are intolerant of hydroxyurea; in adults with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis; and for the treatment of steroid-refractory acute graft-vs-host disease in adult and pediatric patients 12 years and older.
Currently, there is limited evidence on the safety or efficacy of ruxolitinib in the clinical treatment of COVID-19, and ruxolitinib is not currently FDA-approved for this use. Ruxolitinib can cause serious side effects, including infection and certain types of nonmelanoma skin cancer.
