A Study to Evaluate Safety , Efficacy and Pharmacokinetics of WJ01024 Tablets Combined With Ruxolitinib in Patients With Myelofibrosis

Overview

This is a Phase Ib/II clinical study to evaluate the safety , efficacy and pharmacokinetics of WJ01024 tablets combined with Ruxolitinib tablets in patients with myelofibrosis.The study will be conducted in two phases: Phase 1b and Phase 2.Phase Ib is a dose extension study of WJ01024 tablets combined with ruxolitinib tablets. It is planned to recruit patients with medium to high-risk myelofibrosis accompanied by splenomegaly who have had poor response or intolerance to the previously approved JAK inhibitors for myelofibrosis. Phase II is the efficacy extension stage of WJ01024 tablets combined with ruxolitinib Tablets. It is planned to expand two groups of people. Group A will expand to recruit patients with medium-high risk of myelofibrosis accompanied by splenomegaly who have not responded well to the previously approved JAK inhibitors for myelofibrosis. Group B expanded to recruit patients with medium-high-risk myelofibrosis accompanied by splenomegaly who were intolerant after treatment with previously approved JAK inhibitors for myelofibrosis.

Ruxolitinib tablets have been approved in China since April 2017 as the first-line treatment for most intermediate- and high-risk myelofibrosis (MF) patients with splenomegaly. Compared with supportive treatment alone, ruxolitinib tablets have the efficacy of reducing spleen size and improving the symptoms of myelofibrosis, as well as reducing the risk of death and prolonging the survival of MF patients.Although the clinical efficacy of Ruxolitinib tablets has been confirmed, only about half of MF patients can achieve the ideal therapeutic effect (≥35% reduction in spleen volume and ≥50% improvement in disease symptoms at 24 weeks). Therefore, there is an urgent need for innovative drugs that can be combined with Ruxolitinib tablets to enhance therapeutic efficacy and meet clinical needs. WJ01024 is a small molecule inhibitor of XPO-1, belonging to the same target small molecule compounds as Selinexor. Compared with Selinexor, the metabolism rate of this product is faster, which can reduce the toxicity in the body. In the Ba/F3-EPOR-JAK2-V617F cell model, the combination of this product and ruxolitinib tablets can enhance its anti-cell proliferation activity. In a clinical study initiated by researchers, this product has shown preliminary efficacy as a monotherapy in patients with myelofibrosis who have relapsed, are refractory to, or intolerant of JAK inhibitors, and is expected to have fewer toxic and side effects than drugs targeting the same site. Based on this, the following research is planned. This is a Phase Ib/II clinical study to evaluate the safety , efficacy and pharmacokinetics of WJ01024 tablets combined with Ruxolitinib tablets in patients with myelofibrosis.The study will be conducted in two phases: Phase 1b and Phase 2. Phase Ib is a dose extension study of WJ01024 tablets combined with ruxolitinib tablets. It is planned to recruit patients with medium to high-risk myelofibrosis accompanied by splenomegaly who have had poor response or intolerance to the previously approved JAK inhibitors for myelofibrosis. Phase II is the efficacy extension stage of WJ01024 tablets combined with ruxolitinib Tablets. It is planned to expand two groups of people. Group A will expand to recruit patients with medium-high risk of myelofibrosis accompanied by splenomegaly who have not responded well to the previously approved JAK inhibitors for myelofibrosis. Group B expanded to recruit patients with medium-high-risk myelofibrosis accompanied by splenomegaly who were intolerant after treatment with previously approved JAK inhibitors for myelofibrosis.