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

Inclusion Criteria:

Age ≥ 18 years.
Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post-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 Day BL1.
Anemic, defined as a Hgb < 10 g/dL in Screening/Baseline period.
Previously treated with an approved JAK inhibitor for PMF or Post-PV/ET MF for ≥ 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 cm, below the left costal margin, or with volume ≥ 450 cm³ on imaging (ultrasound, MRI or CT are acceptable), assessed during Screening at any point prior to Randomization.
High risk, intermediate-2, or intermediate-1 risk MF as defined by DIPSS, or DIPSS-plus.
No allogeneic stem cell transplant planned.

Acceptable laboratory assessments:

Absolute neutrophil count (ANC) ≥ 0.75 × 10E9/L.
Platelet count (PLT) ≥ 25 × 10E9/L (without requirement for platelet transfusion).
Peripheral blast count < 10%.
Alanine aminotransferase/ glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT) ≤ 3 × ULN (≤ 5 × 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 (CCr) ≥ 30 mL/min according to Cockcroft-Gault.
Direct bilirubin ≤ 2.0 × ULN.

Exclusion Criteria:

Use of the following treatments within the time periods noted:

Prior momelotinib treatment at any time.
Approved JAK inhibitor therapy (eg, fedratinib or ruxolitinib) within 1 week prior to the first day of Baseline.
Active anti-MF therapy within 1 week prior to the first day of Baseline.
Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization.
Investigational agent (including investigational JAK inhibitors) within 4 weeks prior to Randomization.
Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization.
Danazol within 3 months prior to Randomization.
Splenic irradiation within 3 months prior to Randomization.
Current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin.
History of prostate cancer, with the exception of localized prostate cancer that has been treated surgically or by radiotherapy with curative intent and presumed cured.
Prostate specific antigen (PSA) > 4 ng/mL.
Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI 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 (subjects 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.
QTcF interval > 500 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.
Subjects 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 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.