Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants will receive momelotinib plus placebo to match ruxolitinib.

Participants will receive ruxolitinib plus placebo to match momelotinib.

Momelotinib tablet administered orally once daily

Momelotinib

Ruxolitinib tablets administered orally twice daily

Ruxolitinib

Placebo to match momelotinib tablets administered orally once daily

Placebo to match momelotinib

Placebo to match ruxolitinib tablets administered orally twice daily

Placebo to match ruxolitinib

Gilead Study Director

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.

Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis

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)

Splenic response rate at Week 24 is defined as the percentage of participants who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT.

Total symptom score (TSS) is defined as the percentage of participants who achieved a ≥50% reduction in TSS at Week 24 versus baseline as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) v2.0 diary. Response rate was calculated using the average of the daily TSS from a consecutive 28-day period prior to Week 24, which had ≥20 daily TSS available.

The modified MPN-SAF patient-reported outcome instrument consisted of 8 items assessing worst daily incidence of tiredness, filling up quickly, abdominal discomfort, night sweats, itching, bone pain, pain under ribs on left side, and inactivity. Scoring of the Total Symptom Score (TSS), in this study was based on 7 of these items, (range of 0-70,), excluding inactivity. These items assess the impact experienced by the participant in the 24 hours prior to completing the questionnaire. All items are measured using a 0 to 10 Numeric Rating Scale, with 0 corresponding to "Absent" and 10 being the worse

Rate of RBC transfusion was defined as the average number of RBC units transfused not associated with clinically overt bleeding per subject-month during the double-blind phase.

RBC transfusion independence is the percentage 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 12 weeks prior to Week 24, excluding cases associated with clinically overt bleeding.

RBC transfusion dependence is the percentage of participants who are transfusion dependent 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). Participants with the last double-blind phase participation date prior to Day 162 (ie. missing at Week 24) were considered transfusion dependent at Week 24.

Sierra Oncology LLC - a GSK company

The safety population did not include 2 patients (one on MMB and one on RUX) who were not dosed, hence affecting the total number of patients at risk.

Participants received momelotinib plus placebo to match ruxolitinib.

Momelotinib tablets were administered orally once daily at a starting dose of 200 mg.

Additional available strengths included 100 mg and 150 mg. Placebo to match ruxolitinib tablets were administered orally twice daily.

Momelotinib (MMB)

Participants received ruxolitinib plus placebo to match momelotinib.

Ruxolitinib tablets were administered orally twice daily. The dose ranged from 5 to 20 mg BID and was dependent on platelet count, creatinine clearance, and transaminase levels.

Placebo to match momelotinib tablets were administered orally once daily.

Ruxolitinib (RUX)

After completion of the 24-week double-blind treatment phase, participants had the option to receive MMB in an open-label treatment phase for up to an additional 216 weeks. Participants randomized to the MMB group at study entry continued MMB in the open-label treatment phase at their current dose. Available MMB strengths were 100 mg, 150 mg and 200 mg.

MMB to MMB

After completion of the 24-week double-blind treatment phase, participants had the option to receive MMB in an open-label treatment phase for up to an additional 216 weeks. Participants randomized to the RUX group who wished to remain in the study initiated MMB in the open-label treatment phase at the dose matching their equivalent MMB placebo dose. Available MMB strengths were 100 mg, 150 mg and 200 mg.

RUX to MMB

Participants received momelotinib plus placebo to match ruxolitinib.

Momelotinib: Momelotinib tablets were administered orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.

Placebo to match ruxolitinib: Placebo to match ruxolitinib tablets were administered orally twice daily.

Participants received ruxolitinib plus placebo to match momelotinib.

Ruxolitinib: Ruxolitinib tablets were administered orally twice daily. The dose ranged from 5 to 20 mg BID and was dependent on platelet count, creatinine clearance, and transaminase levels.

Placebo to match momelotinib: Placebo to match momelotinib tablets were administered orally once daily

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Asian

Not Permitted

Other

Race/Ethnicity, Customized

Transfusion Dependent

Platelet Count (10^9/L)

Weight

Height

Hemoglobin

GSK Response Center

Participants received momelotinib plus placebo to match ruxolitinib.

Momelotinib tablets were administered orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.

Placebo to match ruxolitinib tablets were administered orally twice daily.

Splenic Response Rate at Week 24

TSS rate analysis at Week 24 only included participants with TSS \> 0 at baseline or with TSS = 0 at baseline but with TSS \> 0 or missing at Week 24.

Total Symptom Score (TSS) Response Rate at Week 24

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)

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)

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)).

Participants received ruxolitinib plus placebo to match momelotinib.

Ruxolitinib tablets were administered orally twice daily (BID). The dose ranged from 5 to 20 mg BID and was dependent on platelet count, creatinine clearance, and transaminase levels.

Placebo to match momelotinib tablets were administered orally once daily.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis	NCT01969838	Primary Myelofi... Post-Polycythem... Post-Essential ...	Momelotinib Ruxolitinib Placebo to matc... Placebo to matc...	18 Years -	Sierra Oncology LLC - a GSK company
Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis	NCT01969838	Primary Myelofi... Post-Polycythem... Post-Essential ...	Momelotinib Ruxolitinib Placebo to matc... Placebo to matc...	18 Years -	Sierra Oncology LLC - a GSK company
Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis	NCT01969838	Primary Myelofi... Post-Polycythem... Post-Essential ...	Momelotinib Ruxolitinib Placebo to matc... Placebo to matc...	18 Years -	Sierra Oncology LLC - a GSK company

Spots Global Cancer Trial Database for placebo to match ruxolitinib