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

Percentage of participants with ≥ 50% reduction in total symptom scores measured by Myelofibrosis Symptom Assessment Form (MFSAF) 4.0 at end of cycle 6.

Subjects with a missing TSS at the end of cycle 6 or who had disease progression before the end of the cycle 6 will be considered non-responders.

MFSAF measures the sum of 7 symptoms on a scale from 0 to 10 (0 being absent and 10 being the worst imagineable). The lower the score the better.

A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment).

The SRRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in SRRs and 95% confidence interval of the difference for fedratinib to BAT.

Percentage of participants who have ≥ 25% spleen volume reduction (SVR) at end of cycle 6

A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment).

The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

Number of participants with all grade adverse events (AEs) and grade 3 to 4 AEs

Number of participants with hematology laboratory abnormalities in the following parameters: hemoglobin (decreased), leukocytes (increase and decrease), lymphocytes (decreased), neutrophils (segmented and band form decreased), Platelets (decreased).

Spleen response rate by palpation is the percentage of participants at the end of cycle 6 with a spleen response according to the IWG-MRT 2013 criteria.

A baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable or A baseline splenomegaly that is palpable at > 10 cm, below the LCM, decreases by ≥ 50%

Participants with a missing spleen size assessment at the end of cycle 6 including those who meet the criteria for progression of splenomegaly before end of cycle 6 will be considered not to be responders.

Durability of spleen volume response (DR) by MRI/CT is defined as the date from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) in spleen volume per the IWG-MRT 2013 criteria or death, whichever is earlier. In the absence of an event before the analysis is performed, the DR will be censored at the date of the last valid assessment performed before the analysis performed date.

Durability of spleen response by palpation (DRP) is defined as time from the date of the first documented palpable spleen response, according to the IWG-MRT 2013 to the date of the subsequent PD in spleen size according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date.

The DSR is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction < 50%. In the absence of TSS reduction < 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.

Number of participants with a CTCAE Grade ≥3 of nausea, diarrhea, or vomiting and any grade wernickes encephalopathy.

Number of participants with thiamine levels below the lower limit of normal

QLQ-C30 - The EORTC QLQ-C30 was developed to assess the quality of life of cancer patients. It consists of 30 items classified into 15 domains including 5 functional subscales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning); 3 multi-item symptom subscales (fatigue, nausea/vomiting, and pain); a global QOL subscale; and 6 single items addressing various symptoms and perceived financial impact. Scores vary from 0 (worst) to 100 (best) for the functional dimensions and GHS, and from 0 (best) to 100 (worst) for the symptom dimensions.

EQ-5D-5L - The EQ-5D-5L is a generic, self-administered preference-based measure of health. The five dimensions covered by the EQ-5D-5L include mobility, self-care, pain, usual activities, and anxiety/depression and is converted into a single summary index that can range from -0.594 to 1.0, with a score of 0 indicating death, 1.00 indicating "full health," and negative scores reflecting states perceived to be worse than death. Respondent's self-rated health on a vertical, 0 to 100 scale where 100 = "Best imaginable health state" and 0 = "Worst imaginable health state"

Time from randomization to death due to any reason or disease progression (modified IWG-MRT 2013 including ≥ 25% increase in spleen volume by MRI/CT).

Time from randomization to death due to any reason