Primary Myelofibrosis (PMF) or Post-Polycythemia Vera or Post- Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)

The primary objective of this study is: •The primary objective of this clinical trial will be to determine the efficacy of MMB compared with ruxolitinib as measured by splenic response rate at Week 24 (SRR24).

Momelotinib Film-Coated Tablets

Momelotinib

Tablet

100 mg, 150 mg and 200 mg

Primary Outcome Measures :
Splenic response rate at Week 24 [ Time Frame: Week 24 ]
Splenic response rate at Week 24 is defined as the proportion of participants achieving a ≥ 35% reduction in spleen volume at Week 24 from baseline as measured by MRI or CT.


Secondary Outcome Measures :
Response rate in total symptom score at Week 24 [ Time Frame: Week 24 ]
Total symptom score (TSS) is defined as the proportion of participants who achieve a ≥ 50% reduction in TSS from baseline to Week 24 as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) v2.0 diary.

Rate of red blood cell (RBC) transfusion through Week 24 [ Time Frame: Baseline to Week 24 ]
Rate of RBC transfusion is defined as the average number of RBC units per participant per month.

RBC transfusion independence rate at Week 24 [ Time Frame: Week 24 ]
RBC transfusion independence is the proportion of participants who are transfusion independent at Week 24, defined as absence of RBC transfusions and no hemoglobin level below 8 g/dL in the prior 12 weeks.

RBC transfusion dependence rate at Week 24 [ Time Frame: Week 24 ]
RBC transfusion dependence is the proportion of participants who are transfusion dependent at Week 24, defined as at least 4 units of RBC transfusions, or a hemoglobin level below 8 g/dL in the prior 8 weeks.

Key Inclusion Criteria:

Palpable splenomegaly at least 5 cm below the left costal margin
Confirmed diagnosis of PMF or post-PV/ET MF
Requires myelofibrosis therapy, in the opinion of the investigator
Classified as high risk OR intermediate-2 risk as defined by the International Prognostic Scoring System (IPSS) for PMF, or intermediate-1 risk (IPSS) associated with symptomatic splenomegaly, hepatomegaly, anemia (hemoglobin < 10.0 g/dL), and/or unresponsive to available therapy
Acceptable laboratory assessment obtained within 14 days prior to the first dose of study drug:

Absolute neutrophil count (ANC) ≥ 0.75 x 10^9/L in the absence of growth factor in the prior 7 days
Platelet Count ≥ 50 x 10^9/L (≥ 100 x 10^9/L if aspartate aminotransferase [AST] or alanine aminotransferase [ALT] is ≥ 2 x the upper limit of the normal range [ULN]) in the absence of platelet transfusion(s) or thrombopoietin mimetics in the prior 7 days
Peripheral blood blast count < 10%
AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
Calculated creatinine clearance (CrCL) of ≥ 45 mL/min
Direct bilirubin ≤ 2.0 x ULN
Life expectancy of > 24 weeks
Males and females of childbearing potential must agree to use protocol-specified method(s) of contraception
Females who are nursing must agree to discontinue nursing before the first dose of study drug
Able to understand and willing to sign the informed consent form

Key Exclusion Criteria:

Prior splenectomy
Splenic irradiation within 3 months prior to the first dose of study drug
Eligible for allogeneic bone marrow or stem cell transplantation
Uncontrolled inter-current illness, per protocol.
Known positive status for human immunodeficiency virus (HIV)
Chronic active or acute viral hepatitis A, B, or C infection, or a hepatitis B or C carrier
Prior use of a JAK1 or JAK2 inhibitor
Use of chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or investigational therapy within 4 weeks of the first dose of study drug
Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
Unwilling or unable to undergo a magnetic resonance imaging (MRI) or computed tomography (CT) scan
Note: Other protocol defined Inclusion/Exclusion criteria may apply.