Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis
Condition: Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis
MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: Momelotinib; Ruxolitinib; Placebo to match momelotinib; Placebo to match ruxolitinib
Intervention description: Momelotinib tablet administered orally once daily; Ruxolitinib tablets administered orally twice daily; Placebo to match momelotinib tablets administered orally once daily; Placebo to match ruxolitinib tablets administered orally twice daily
Intervention MeSH terms: N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 432.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib (RUX) in
      participants with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential
      thrombocythemia myelofibrosis (post-PV/ET MF) who have not yet received treatment with a
      Janus kinase inhibitor (JAK inhibitor).

      Participants will be randomized to receive either MMB or ruxolitinib for 24 weeks during a
      double-blind treatment phase, after which they will be eligible to receive open-label MMB for
      up to an additional 216 weeks. After discontinuation of study medication, assessments will
      continue for 12 additional weeks, after which participants will be contacted for survival
      follow-up approximately every 6 months for up to 5 years from the date of enrollment or until
      study termination. For those participants planning to continue treatment with MMB following
      the end of the study, the Early Study Drug Discontinuation (ESDD), 30-day, 12-Week, and
      survival follow-up visits are not required.
    

Eligibility criteria:

        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.