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Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01969838
First received: October 22, 2013
Last updated: October 27, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Drug: Momelotinib
Drug: Ruxolitinib
Drug: Placebo to match momelotinib
Drug: Placebo to match ruxolitinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Splenic response rate at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Splenic response rate at Week 24 is defined as the proportion of participants achieving a ≥ 35% reduction in spleen volume at Week 24 from baseline as measured by MRI or CT.


Secondary Outcome Measures:
  • Response rate in total symptom score at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Total symptom score (TSS) is defined as the proportion of participants who achieve a ≥ 50% reduction in TSS from baseline to Week 24 as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) v2.0 diary.

  • Rate of red blood cell (RBC) transfusion through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Rate of RBC transfusion is defined as the average number of RBC units per participant per month.

  • RBC transfusion independence rate at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    RBC transfusion independence is the proportion of participants who are transfusion independent at Week 24, defined as absence of RBC transfusions and no hemoglobin level below 8 g/dL in the prior 12 weeks.

  • RBC transfusion dependence rate at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    RBC transfusion dependence is the proportion of participants who are transfusion dependent at Week 24, defined as at least 4 units of RBC transfusions, or a hemoglobin level below 8 g/dL in the prior 8 weeks.


Estimated Enrollment: 420
Study Start Date: October 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Momelotinib
Participants will receive momelotinib plus placebo to match ruxolitinib.
Drug: Momelotinib
Momelotinib tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387
Drug: Placebo to match ruxolitinib
Placebo to match ruxolitinib tablets administered orally twice daily
Active Comparator: Ruxolitinib
Participants will receive ruxolitinib plus placebo to match momelotinib.
Drug: Ruxolitinib
Ruxolitinib tablets administered orally twice daily
Drug: Placebo to match momelotinib
Placebo to match momelotinib tablets administered orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01969838

Contacts
Contact: Clinical Study Team momelotinib.studies@gilead.com

  Show 44 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Peter Lee, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01969838     History of Changes
Other Study ID Numbers: GS-US-352-0101, 2013-002707-33
Study First Received: October 22, 2013
Last Updated: October 27, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Mexico: Federal Commission for Protection Against Health Risks
Singapore: Health Sciences Authority
Taiwan : Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Israel: Israeli Health Ministry Pharmaceutical Administration
Russia: Ministry of Health of the Russian Federation
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocythemia, Essential
Thrombocytosis
Blood Coagulation Disorders
Blood Platelet Disorders
Bone Marrow Diseases
Hematologic Diseases
Hemorrhagic Disorders
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on November 27, 2014