Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis (Simplify 1)

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.