A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)

Inclusion Criteria

• Age >= 18 years.
• Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post- polycythemia vera/essential thrombocythemia (PV/ET) MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT criteria).
• Symptomatic, defined as a TSS of >= 10 units assessed by a single MFSAF v4.0 assessment during Screening prior to Baseline period (Day BL1).
• Anemic, defined as a Hgb = 90 days, or >= 28 days if JAK inhibitor therapy is complicated by RBC transfusion requirement of >= 4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma.
• Baseline splenomegaly, defined as having a palpable spleen at >= 5 centimeter (cm), below the left costal margin, or with volume >= 450 cubic centimeter (cm^3) on imaging (ultrasound, magnetic resonance imaging [MRI] or computed tomography [CT] are acceptable), assessed during Screening at any point prior to Randomization.
• High risk, intermediate-2, or intermediate-1 risk MF as defined by Dynamic International Prognostic Scoring System (DIPSS), or DIPSS-plus.
• No allogeneic stem cell transplant planned.
• Acceptable laboratory assessments:
• Absolute neutrophil count (ANC) >= 0.75 × 10^9/Liter (L).
• Platelet count (PLT) >= 25 × 10^9/L (without requirement for platelet transfusion).
• Peripheral blast count = 30 milliliter per minute (mL/min) according to Cockcroft-Gault.
• Direct bilirubin 4 nanograms per milliliter (ng/mL).
• Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI scan or CT scan for spleen volume measurement per protocol requirements.
• Any of the following (criteria a - k):
• Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial).
• Significant active or chronic bleeding event >= Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization.
• Unstable angina pectoris within 6 months prior to Randomization.
• Symptomatic congestive heart failure within 6 months prior to Randomization.
• Uncontrolled cardiac arrhythmia within 6 months prior to Randomization.
• QT Interval Corrected Using Fridericia's Formula (QTcF) interval > 500 millisecond (msec), unless attributed to bundle branch block.
• Current progressive thrombosis despite treatment.
• History of porphyria.
• Child-Pugh score >= 10.
• Psychiatric illness, social situation, or any other condition that would limit compliance with trial requirements or may interfere with the interpretation of study results, as judged by investigator or sponsor.
• Inability or unwillingness to comply with the protocol restrictions on MF therapy and other medications prior to and during study treatment.
• Participants with a prior or concurrent malignancy, whose natural history or treatment has a significant potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding or thalassemia.
• Known positive status for human immunodeficiency viruses (HIV).
• Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier (testing required for hepatitis B and C).
• Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per CTCAE v5.0.
• Presence of peripheral neuropathy >= Grade 2 per CTCAE v5.0.
• Women who are already pregnant or lactating. Additional inclusion/exclusion criteria may apply.