Overview

This trial is active, not recruiting.

Conditions primary myelofibrosis, post-polycythemia vera myelofibrosis, post-essential thrombocythemia myelofibrosis
Treatments momelotinib, ruxolitinib, placebo to match momelotinib, placebo to match ruxolitinib
Phase phase 3
Targets JAK, JAK1, JAK2
Sponsor Gilead Sciences
Start date December 2013
End date September 2016
Trial size 432 participants
Trial identifier NCT01969838, 2013-002707-33, GS-US-352-0101

Summary

This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib 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 168 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will receive momelotinib plus placebo to match ruxolitinib.
momelotinib GS-0387
Momelotinib tablet administered orally once daily
placebo to match ruxolitinib
Placebo to match ruxolitinib tablets administered orally twice daily
(Active Comparator)
Participants will receive ruxolitinib plus placebo to match momelotinib.
ruxolitinib
Ruxolitinib tablets administered orally twice daily
placebo to match momelotinib
Placebo to match momelotinib tablets administered orally once daily

Primary Outcomes

Measure
Splenic response rate at Week 24
time frame: Week 24

Secondary Outcomes

Measure
Response rate in total symptom score at Week 24
time frame: Week 24
Rate of red blood cell (RBC) transfusion through Week 24
time frame: Baseline to Week 24
RBC transfusion independence rate at Week 24
time frame: Week 24
RBC transfusion dependence rate at Week 24
time frame: Week 24

Eligibility Criteria

Male or female participants at least 18 years old.

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 < 10.0 g/dL), and/or unresponsive to available therapy - Acceptable laboratory assessment obtained within 14 days prior to the first dose of study drug: - Absolute neutrophil count (ANC) ≥ 0.75 x 10^9/L in the absence of growth factor in the prior 7 days - Platelet Count ≥ 50 x 10^9/L (≥ 100 x 10^9/L if aspartate aminotransferase [AST] or alanine aminotransferase [ALT] is ≥ 2 x the upper limit of the normal range [ULN]) in the absence of platelet transfusion(s) or thrombopoietin mimetics in the prior 7 days - Peripheral blood blast count < 10% - AST and ALT ≤ 3 x 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 (CrCL) of ≥ 45 mL/min - Direct bilirubin ≤ 2.0 x ULN - Life expectancy of > 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 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

Additional Information

Official title A Phase 3, Randomized, Double-blind Active-controlled Study Evaluating Momelotinib vs. Ruxolitinib in Subjects With Primary Myelofibrosis (PMF) or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.