Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis. MedDRA version: 17.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Momelotinib 200mg
Product Code: GS-0387
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: momelotinib dihydrochloride monohydrate
Current Sponsor code: GS-0387-01 monohydrate
Sponsors
Gilead Sciences Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years old 2) Palpable splenomegaly at least 5 cm below left costal margin 3) Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) criteria, or Post-PV/ET MF in accordance with the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria 4) Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days and characterized by: - Requirement for red blood cell (RBC) transfusion while on ruxolitinib treatment, or - Dose adjustment of ruxolitinib to 0.75 x 10^9/L in the absence of growth factor in the prior 7 days - Peripheral blood blast count 24 weeks 11) Negative serum pregnancy test for female subjects (unless surgically sterile or greater than 2 years post-menopausal) 12) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception 13) Females who are nursing must agree to discontinue nursing before the first dose of MMB 14) Able to understand and willing to sign informed consent form (ICF) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1) Prior splenectomy 2) Splenic irradiation within 3 months prior to Day 1 3) Use of investigational agent within 28 days prior to Day 1 4) Prior treatment with MMB 5) Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) within 28 days prior to Day 1 6) 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 study); active or chronic bleeding event within 4 weeks prior to Day 1; symptomatic congestive heart failure (CHF); unstable angina pectoris; uncontrolled cardiac arrhythmia; or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician 7) QTc interval > 450 msec, unless attributed to bundle branch block 8) History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for = 1 year prior to randomization, adequately treat Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for = 5 years 9) Known positive status for human immunodeficiency virus (HIV) 10) Chronic active or acute viral hepatitis A. B or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier 11) Unresolved non-hematologic toxicities from prior therapies that are > CTCAE Grade 1 12) Use of strong CYP3A4 inhibitors or strong CYP3A4 inducers within 1 week prior to Day 1 13) Changes to dose of iron chelator therapy within 14 days prior to Day 1 14) Presence of peripheral neuropathy = CTCAE Grade 2 15) Unwilling or unable to undergo a MRI or CT Scan 16) Known hypersensitivity to MMB, the metabolites, or formulation excipients
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Response rate in total symptom score (TSS) from Baseline to Week 24 - defined as the proportion of subjects who achieves a = 50 % reduction from Baseline in total symptom score to Week 24 as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF) TSS v2.0 diary - Rate of RBC transfusion - defined as the average number of RBC units per subject-month during the study period (through Week 24) - RBC transfusion independence rate at Week 24 - defined as the proportion of subjects who is transfusion independent at Week 24, where transfusion independence is defined as absence of RBC transfusion and no hemoglobin (Hgb) level below 8 g/dL in the prior 12 weeks - RBC transfusion dependence rate at Week 24 - defined as the proportion of subjects who is transfusion dependent at Week 24, where transfusion dependence is defined as at least 4 units of RBS transfusions, or a Hgb level below 8 g/dL, in the prior 8 weeks;Timepoint(s) of evaluation of this end point: Week 24 | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of momelotinib (MMB) versus best available therapy (BAT) in anemic or thrombocytopenic subjects with primary myelofibrosis (PMF), or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/EF MF) who were treated with ruxolitinib as measured by splenic response rate at Week 24 (SRR24).;Secondary Objective: - To determine the effect of MMB compared with BAT on the improvement of total symptom score (TSS) on Week 24 - To determine the effect of MMB compared with BAT on rate of red blood cell (RBC) transfusion through Week 24 - To determine the effect of MMB compared with BAT on RBC transfusion independance rate at Week 24 - To determined the effect of MMB compared with BAT on RBC transfusion dependance rate at Week 24;Primary end point(s): The primary endpoint is SRR24 - defined as the proportion of subjects who achieves a = 35 % reduction in spleen volume at Week 24 from baseline as measure by MRI or CT;Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Canada, France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactInternational Regulatory Affairs
Gilead Sciences International Ltd
Outcome results
None listed