An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib

This Phase 3, multicenter, randomized, two-arm, open-label study will include subjects with intermediate or high-risk (as per the DIPSS score) primary myelofibrosis (PMF), postpolycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF). This study will be conducted in compliance with International Council for Harmonisation (ICH) Good Clinical Practices (GCPs).

Study design includes:

* A 28-day Screening Period * 2:1 Randomization to fedratinib or best available therapy (BAT) * Stratification at Randomization according to:

* Spleen size by palpation: \< 15 cm below left costal margin (LCM) versus ≥ 15 cm below LCM * Platelets ≥ 50 to \< 100 x 109/L versus platelets ≥ 100 x 109/L * Refractory or relapsed to ruxolitinib treatment versus intolerant to ruxolitinib treatment * Study Treatment Period (time on study drug plus 30 days after last dose) * Subjects are allowed to crossover from BAT to the fedratinib arm after the Cycle 6 response assessment or before the Cycle 6 response assessment in the event of a confirmed progression of splenomegaly by MRI/CT scan * A Survival Follow-up Period for progression and survival