Cell Therapeutics, Inc. (CTI) has announced the initiation of a Phase 3 clinical trial, known as PERSIST-2, which will evaluate pacritinib, a novel, investigational JAK2/FLT3 inhibitor, in patients with myelofibrosis whose platelet counts are less than or equal to 100,000 per microliter (uL).
The trial is expected to enroll up to 300 patients in North America, Europe, Australia and New Zealand within 12 to 14 months. In October 2013, CTI reached agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the PERSIST-2 trial, which is a written agreement between CTI and the FDA regarding the planned design, endpoints and statistical analysis approach of the trial to be used in support of a potential New Drug Application, or NDA, submission. PERSIST-2 is the second of two planned Phase 3 trials in the pacritinib development program for myelofibrosis.
"JAK2 inhibitors have revolutionized the treatment of myelofibrosis by providing patients with an effective way to manage their disease," said Srdan Verstovsek, MD, PhD, principal investigator of PERSIST-2 and Professor, Leukemia Department, Division of Cancer Medicine, Chief, Section for Myeloproliferative Neoplasms, Leukemia Department, and Director, Clinical Research Center for MPNs, at The University of Texas MD Anderson Cancer Center. "However, I believe there remains a significant unmet medical need for new therapies, particularly for patients who present with or develop thrombocytopenia while on treatment. We are pleased to have the PERSIST-2 trial underway to evaluate the ability of pacritinib to address this issue."
PERSIST-2 is a randomized, open-label, multi-center clinical trial evaluating pacritinib in patients with myelofibrosis (a myeloproliferative neoplasm and chronic bone marrow disorder) whose platelet counts are less than or equal to 100,000/uL.
The trial will evaluate pacritinib as compared to best available therapy, including approved JAK2 inhibitors that are dosed according to the product label for myelofibrosis patients with thrombocytopenia. Patients will be randomized (1:1:1) to receive 200 mg pacritinib twice daily (BID), 400 mg pacritinib once daily (QD) or best available therapy.
Under the SPA, the agreed upon co-primary endpoints are the percentage of patients achieving a 35 percent or greater reduction in spleen volume measured by MRI or CT scan from baseline to 24 weeks of treatment and the percentage of patients achieving a Total Symptom Score (TSS) reduction of 50 percent or greater using six key symptoms as measured by the modified Myeloproliferative Neoplasm Symptom Assessment (MPN-SAF TSS 2.0) diary from baseline to 24 weeks. Additional trial details are available at www.clinicaltrials.gov.
"With the initiation of the PERSIST-2 trial, we believe that the registration program for pacritinib is on track for a potential NDA submission in the latter part of 2015," said James A. Bianco, MD, President and CEO of CTI. "We have seen meaningful clinical benefits and good tolerability with pacritinib in myelofibrosis patients in Phase 2 trials without apparent drug-related thrombocytopenia or anemia. As such, we have had strong interest in site participation for this trial and will work diligently to activate these sites over the next several months."
Pacritinib Development Program in Myelofibrosis
Based on pacritinib's efficacy and tolerability profile demonstrated to date, CTI is pursuing a broad approach to advancing this therapy for myelofibrosis patients by conducting two Phase 3 clinical trials: one in a broad set of patients without limitations on blood platelet counts, the ongoing PERSIST-1 trial, and the other in patients with low platelet counts, the PERSIST-2 trial, as described above.
In January 2013, CTI initiated PERSIST-1, which is a 270 patient randomized, open-label, multicenter Phase 3 trial comparing the efficacy and safety of pacritinib with that of best available therapy in patients with myelofibrosis. Best available therapy includes any physician-selected treatment other than JAK inhibitors and there is no exclusion by patient platelet count.
The trial is currently enrolling patients at clinical sites in Europe, Australia, Russia and the United States.