A Study of Momelotinib in Participants With Low-risk Myelodysplastic Syndrome

Eligibility Criteria

• * Documented diagnosis of MDS according to the World Health Organization classifications with an Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease, with an overall risk score ≤3.5.
• * Received prior treatment with Erythropoiesis-stimulating agent (ESA) OR luspatercept for LR-MDS-related anemia that is relapsed/refractory to therapy. Participants intolerant to prior ESA or luspatercept will fulfill this inclusion criterion provided the definition below is met.
• * Red blood cell transfusion dependence, defined as requiring an average of ≥4 units of Packed red blood cells (pRBC) transfused over an 8-week period during the 16 weeks preceding randomization. Documentation of a participant's transfusion policy during this 16-week period is required.
• * A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
• * Is capable of giving signed informed consent.
• * Eastern Cooperative Oncology Group performance status ≤2.
• * Adequate organ function.
• 1. Janus kinase (JAK)1/2 inhibitors; ACTRIIb IMiDs (iif ≤1 week of treatment received; provided last dose was ≥8 weeks from randomization
• 2. ACTRIIb receptor ligand trap other than luspatercept
• 3. Hypomethylating agents or other disease modifying agents (i.e., IMiDs) and immunosuppressive therapy for MDS
• 4. ESA within 4 weeks, or 8 weeks for long-acting ESA.
• 5. Growth factors (i.e., G-CSF, GM-CSF) within 4 weeks.
• 6. Luspatercept within 8 weeks.
• 7. Investigational agents within 4 weeks or 5 half-lives, whichever is longer.
• 8. Corticosteroids for treatment of the underlying disease within 28 days. Supportive care use of steroids for non-MDS indications may be used provided participant is on a stable dose equivalent to ≤10 mg prednisone per day.
• 9. Other active anti-MDS therapy not otherwise listed within 28 days or 5 half-lives whichever is longer.
• 10. Potent cytochrome P450 3A4 (CYP3A4) inducers, except for rifampin and rifampicin, within 14 days prior to the first dose of momelotinib.
• 11. Has received a live vaccine within 30 days. • Prior allogeneic or autologous stem cell transplant. • Has had any major surgery within 28 days prior to randomization. • Ongoing adverse reaction(s) from prior therapy that have not recovered to ≤Grade 1 or to the baseline status preceding prior therapy, except if the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• * MDS associated with del 5q cytogenetic abnormality.
• * Secondary MDS (i.e., MDS that is known to have arisen as the result of chemical injury, treatment with chemotherapy, and/or radiation for other diseases).
• * Known history of diagnosis of acute myeloid leukemia.
• * Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, gastrointestinal bleeding, or thalassemia.
• * Diagnosis of invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years, except as noted below:
• 1. History of an invasive malignancy for which the participant was definitively treated, and in which the participant has been disease free for at least 2 years, and which, in the opinion of the principal investigator and medical monitor, is not expected to affect the evaluation of the effects of the study intervention on the currently targeted disease under study.
• 2. Curatively treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, and/or in situ breast cancer may be enrolled.
• 3. Incidental histologic finding of prostate cancer (T1a or T1b using the Tumor, nodes, metastasis \[TNM\] clinical staging system).
• * Uncontrolled intercurrent illness including, but not limited to:
• 1. Unstable angina pectoris.
• 2. Symptomatic congestive heart failure.
• 3. Uncontrolled cardiac arrhythmia. • QTc interval \>480 milliseconds (msec) (corrected using Fridericia formula).
• * Is unable to swallow and/or retain oral medications.
• * Known contraindication or hypersensitivity to momelotinib and its metabolites, or any of their excipients.