Phase III Trial of Pacritinib Initiated for Treatment of Severe COVID-19

John Mascarenhas, MD

The phase III PRE-VENT clinical trial of pacritinib as treatment for hospitalized patients with severe coronavirus disease 2019 (COVID-19) has been initiated, according to an announcement from CTI BioPharma. Pacritinib has been explored primarily for the treatment of patients with myelofibrosis.

PRE-VENT will determine the ability of pacritinib to prevent progression to acute respiratory distress syndrome and mechanical ventilation.

“Patients with severe COVID-19, particularly those with cancer, are at high risk for serious complications from the disease stemming from cytokine storm, an inflammatory response that causes white blood cells to not only fight the viral infection, but also damage tissue, primarily in the lungs," said John Mascarenhas, MD, associate professor, Medicine, Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York and chief investigator of the PRE-VENT Study, said in a statement. "Because pacritinib inhibits JAK2, IRAK-1, and CSF1R, there is real potential for pacritinib to prevent patients from developing an inflammatory response to the coronavirus infection and subsequent pulmonary failure, therefore reducing the need for a ventilator."

Enrollment to the PRE-VENT trial is expected to commence in May 2020 across sites in both the United States and Europe. Data is expected by the end of 2020.

PRE-VENT is a randomized, double-blind, placebo-controlled, multicenter trial that will compare treatment with pacritinib in addition to the standard of care (SoC) versus placebo and SoC in 358 patients. The primary end point of the trial is the proportion of patients who progress to invasive mechanical ventilation and/or extracorporeal membrane oxygenation or die by Day 28.

Patients will be randomized to receive SoC with either placebo or pacritinib at 400 mg once on day 1 followed by twice daily from day 2 to day 14 or until intolerable adverse events, withdrawal of consent, initiation of another investigational therapy, or termination of the study. The assigned therapy can also be administered to the patient for an additional 7 days to complete a total of 21 days at the discretion of the investigator. Patients will complete treatment with the assigned therapy as an outpatient if they are discharged from the hospital while in the trial.

An interim analysis is expected to be conducted after 154 patients have been enrolled in the study. Investigators will also assess safety through 30 days of follow-up after the last dose is administered and assessed by cumulative incidence, severity, and seriousness of treatment-emergent adverse events, drug discontinuations, laboratory values, and clinical assessments.

Pacritinib is an oral kinase inhibitor specific to JAK2, IRAK1, and SCR1R. The JAK family is critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. The mutations in these kinases appear to be directly related to the development of a variety of blood cancers, such as myeloproliferative neoplasms, leukemia, and lymphoma. The profile of pacritinib also suggests potential utility in inflammatory and immune-mediated disorders, such as acute graft-versus-host disease.

Ruxolitinib (Jakafi), another JAK inhibitor, is under investigation for the treatment of patients with severe COVID-19 as well. The agent is being evaluated in the phase III RUXCOVID clinical trial, in which ruxolitinib is used in combination with SoC compared with placebo.

Clinical trials are also enrolling patients with COVID-19 to evaluate other oncology drugs that have potential therapeutic benefit for this patient population, including leronlimab in a phase IIb/III trial, acalabrutinib (Calquence) in the CALAVI trial, and low-dose selinexor (Xpovio) in a clinical trial.

"Given the unprecedented medical need to improve outcomes for patients with COVID-19, we have made a commitment to test pacritinib, a JAK2/IRAK-1/CSF-1R inhibitor, in hospitalized patients with severe COVID-19, with the goal of preventing progression to acute respiratory distress syndrome and mechanical ventilation," stated Adam R. Craig, MD, PhD, president and chief executive officer of CTI Biopharma. "Emerging evidence suggests that the attenuation of the cytokine storm associated with COVID-19 could be a potential treatment approach for this devastating disease, and it is hypothesized that pacritinib may have a role in treating these patients.”

Reference

CTI Biopharma Announces Initiation of Phase 3 PRE-VENT Study Evaluating Pacritinib in Hospitalized Patients with Severe COVID-19 [news release]. Seattle, WA: CTI BioPharma; April 27, 2020. https://prn.to/2Se10Cs. Accessed April 28, 2020.