Ruxolitinib Phase III Trial Initiated for Treatment of COVID-19 Cytokine Storm

The global phase III RUXCOVID clinical trial evaluating ruxolitinib (Jakafi) in combination with standard of care for the treatment of cytokine storm associated with coronavirus disease 2019 (COVID-19) in patients 12 years and older has been initiated, announced Incyte. This is the first randomized, placebo-controlled phase III study to evaluate the efficacy and safety of this indication.

In addition to the initiate of this trial, the company also initiated a separate emergency Expanded Access Program (EAP) in the United States. The EAP will allow patients who are eligible with severe cytokine storm associated with COVID-19 to receive the agent while it remains under investigation. To qualify for the EAP, patients must be unable to participate in any other clinical trial of ruxolitinib in COVID-19.

“There is an unprecedented unmet medical need for treatments that prevent or reduce severe COVID-19 related complications to improve outcomes for patients and alleviate the overwhelming pressure on the global healthcare system,” said Steven Stein, MD, chief medical officer, Incyte. “We thank the FDA for the expedited review of the RUXCOVID study and hope to enroll this important clinical trial as quickly as possible to determine the potential utility of ruxolitinib for treatment of patients with severe COVID-19 associated cytokine storm.”

The trial will evaluate the efficacy and safety of ruxolitinib. Incyte announced their plans to explore ruxolitinib for this indication in early April, as well as their plans to open an emergency EAP for patients in urgent need to receive ruxolitinib treatment for COVID-19 associated cytokine storm.

The double-blind study will randomize patients 2:1 to receive either oral ruxolitinib at 5 mg twice daily with the standard of care therapy of investigator’s choice or an oral-matching placebo for 14 days. Patients will be able to continue treatment for an additional 14 days of the study therapy should clinical signs not improve, symptoms worsen after the initial 14 days on the study, and if the potential benefit outweighs the potential risks.

Patients will be followed for a total of 29 days following the randomization to ruxolitinib or placebo. The primary end point is the proportion of patients who die, develop respiratory failure, or require intensive care unit (ICU) care by day 29. Secondary end points include evaluation of clinical status on a 9-point ordinal scale, in-hospital outcomes, change in the National Early Warning Score, change in SpO2/FiO2, the proportion of patients with no oxygen therapy, and safety. In-hospital outcomes are evaluated by the mortality rate, proportion of patients that require mechanical ventilation, and the duration of hospitalization, ICU stay, supplemental oxygen, and invasive mechanical ventilation.

Cytokine storm, a severe immune overreaction triggered by COVID-19, can lead to serious complications in patients with COVID-19, such as pneumonia and acute reparatory distress syndrome. These patients often require intensive care due to cytokine storm, such as intubation and mechanical ventilation. These patients are at an increased risk of mortality.

Regulating overactive signaling in the JAK-STAT pathway during cytokine storm may be a potential treatment approach based on emerging data of COVID-19. Ruxolitinib is expected to play a role in the treatment of these patients. However, the clinical evidence of the safety and efficacy of ruxolitinib for this indication is limited.

Ruxolitinib has been previously approved by the FDA for the treatment of patients with polycythemia vera (PV) who have had an inadequate response or intolerant to hydroxyurea, as well as in adult patients with intermediate- or high-risk myelofibrosis (MF), which included primary MF, post-PV MF, and post-essential thrombocytopenia MF. Ruxolitinib has also been approved for the treatment of steroid-refractory acute graft-versus-host-disease in adult and pediatric patients 12 years and older.

_Reference

_{Incyte Announces Initiation of Phase 3 RUXCOVID Study Evaluating Ruxolitinib (Jakafi) as a Treatment for Patients with COVID-19 Associated Cytokine Storm [news release]. Wilmington, DE: Incyte; April 17, 2020. LINK. Accessed April 21, 2020.}