Phase 3
N=432
Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis
Primary Myelofibrosis · Post-Polycythemia Vera Myelofibrosis · Post-Essential Thrombocythemia Myelofibrosis
Bottom Line
View on ClinicalTrials.gov: NCT01969838 ↗Enrolled (actual)
432
Serious AEs
30.8%
Results posted
May 2023
Primary outcome: Primary: Splenic Response Rate at Week 24 — 57; 64; 158; 153 Participants — p=0.014
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Momelotinib (Drug); Ruxolitinib (Drug); Placebo to match momelotinib (Drug); Placebo to match ruxolitinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Sierra Oncology LLC - a GSK company
- Primary completion
- Sep 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Splenic Response Rate at Week 24 |
57; 64; 158; 153 | 0.014 sig |
| SECONDARY Total Symptom Score (TSS) Response Rate at Week 24 |
60; 89; 151; 122 | 0.98 |
| SECONDARY Rate of Red Blood Cell (RBC) Transfusions in the Double-blind Phase, (the Average Number of RBC Units Transfused Per Month Not Associated With Overt Bleeding) |
0.0; 0.4 | <0.001 sig |
| SECONDARY RBC Transfusion Independence Rate at Week 24, (Defined as Absence of RBC Transfusions and no Hemoglobin Level Below 8 g/dL in the 12 Weeks Prior to Week 24, Excluding Cases Associated With Clinically Overt Bleeding) |
143; 107; 72; 110 | <0.001 sig |
| SECONDARY RBC Transfusion Dependence Rate at Week 24. (Defined as Having Had at Least 4 Units of RBC Transfusions, or a Hemoglobin Level Below 8 g/dL in 8 Weeks Prior to Week 24 (Excluding Cases Associated With Clinically Overt Bleeding)). |
65; 87; 150; 130 | 0.019 sig |
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 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.
Data sourced from ClinicalTrials.gov (NCT01969838). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.