Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF (Simplify 2)

This is an interventional treatment trial for Primary Myelofibrosis (PMF) Read More

Key Inclusion Criteria:

• Palpable splenomegaly at least 5 cm below left costal margin
• Confirmed diagnosis of PMF in accordance, or Post-PV/ET MF

• Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days, and characterized by

  • Requirement for RBC transfusion while on ruxolitinib treatment, OR

  • Dose adjustment of ruxolitinib to < 20 mg twice daily at start of or during ruxolitinib treatment AND at least one of the following while on ruxolitinib treatment:

    • ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 thrombocytopenia, OR
    • ≥ CTCAE Grade 3 anemia, OR
    • ≥ CTCAE Grade 3 hematoma (bleed)
• High risk OR intermediate-2 risk as defined by Dynamic International Prognostic Scoring System (DIPSS), OR intermediate-1 risk as defined by DIPSS and associated with symptomatic splenomegaly, and/or hepatomegaly
• If receiving myelofibrosis therapy, must be on a stable dose of the same regimen for at least 2 weeks prior to screen date and through the screening period
• If not receiving myelofibrosis therapy, must remain off therapy for at least 2 weeks prior to screen date and through the screening period

• Acceptable laboratory assessments obtained within 14 days prior to Randomization

  • Absolute neutrophil count (ANC) > 0.75 x 10^9/L in the absence of growth factor in the prior 7 days
  • Peripheral blood blast count < 10%
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the upper limit of the normal range (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 of ≥ 45 mL/min
  • Direct bilirubin ≤ 2.0 x ULN
• Life expectancy > 24 weeks
• Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years post-menopausal)
• 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 MMB
• Able to understand and willing to sign informed consent form (ICF)

Key Exclusion Criteria:

• Prior splenectomy
• Splenic irradiation within 3 months prior to Randomization
• Use of investigational agent within 28 days prior to Randomization
• Prior treatment with MMB
• Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) within 28 days prior to Randomization
• 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 hepatitis B or C carrier
• Presence of peripheral neuropathy ≥ CTCAE Grade 2
• Unwilling or unable to undergo a MRI or CT Scan per study protocol requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply.