The FDA has approved a randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the safety and efficacy of intravenous (IV) tocilizumab (Actemra) plus standard of care in hospitalized adult patients with severe coronavirus disease 2019 (COVID-19) pneumonia, 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 versus placebo plus standard of care.
Genentech has also indicated that they will provide 10,000 vials of tocilizumab to the US Strategic National Stockpile for future use at the direction of the US Department of Health and Human Services to further support the COVID-19 response efforts.
“We thank the FDA for rapidly expediting the approval of this clinical trial to evaluate Actemra in critically ill patients suffering from pneumonia following coronavirus infection and we’re moving forward to enroll as quickly as possible,” Alexander Hardy, chief executive officer of Genentech, said in a press release. “Conducting this clinical trial in partnership with BARDA and providing Actemra to support the national stockpile, through the efforts of Secretary Azar and HHS, are important examples of how the US government, the biotechnology industry, and healthcare communities are working together in response to this public health crisis.”
According to Genentech, COVACTA is the first global trial in this setting. Enrollment is anticipated to start as early as April 2020, with a target accrual of 330 patients across the US 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 post-randomization, 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 suffering from COVID-19.
Currently, tocilizumab is not approved for use by the FDA in COVID-19 patients. Further, the US supply of tocilizumab for already approved indications is not expected to be affected.
Tocilizumab alters the way a patient’s immune system works, and this has the potential to make a patient more likely to get infections or make any current infection worse. Moreover, some people taking tocilizumab have died from such infections.
Common side effects observed in patients treated with tocilizumab include:
- Upper respiratory tract infections
- Injection site reactions
Tocilizumab is also known to cause serious side effects, including:
- Tears of the stomach or intestines
- Liver problems (hepatotoxicity)
- Changes in blood test results, including low neutrophil and platelet counts, and increases in certain liver function test levels and blood cholesterol levels
- An increased risk of certain cancers by changing the way a patient’s immune system works
- Hepatitis B infection
- Serious allergic reactions, including death
- Nervous system problems
Tocilizumab is already approved by the FDA for the treatment of cytokine release syndrome (CRS) that is severe or life-threatening. The agent is used in adults and children aged 2 years and older who have CRS caused by CAR 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.
Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat Hospitalized Patients with Severe COVID-19 Pneumonia [news release].