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Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis (Simplify 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01969838
Recruitment Status : Completed
First Posted : October 25, 2013
Last Update Posted : April 15, 2020
Sponsor:
Information provided by (Responsible Party):
Sierra Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE October 22, 2013
First Posted Date  ICMJE October 25, 2013
Last Update Posted Date April 15, 2020
Actual Study Start Date  ICMJE December 6, 2013
Actual Primary Completion Date September 12, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2013)
Splenic response rate at Week 24 [ Time Frame: Week 24 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2014)
  • Response rate in total symptom score at Week 24 [ Time Frame: Week 24 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2013)
  • Rate of red blood cell (RBC) transfusion through Week 24 [ Time Frame: Baseline to Week 24 ]
    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 ]
    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 ]
    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.
  • Response rate in total symptom score at Week 24 [ Time Frame: Week 24 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis
Official Title  ICMJE 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)
Brief 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 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Myelofibrosis
  • Post-Polycythemia Vera Myelofibrosis
  • Post-Essential Thrombocythemia Myelofibrosis
Intervention  ICMJE
  • Drug: Momelotinib
    Momelotinib tablet administered orally once daily
    Other Names:
    • GS-0387
    • CYT387
  • Drug: Ruxolitinib
    Ruxolitinib tablets administered orally twice daily
  • Drug: Placebo to match momelotinib
    Placebo to match momelotinib tablets administered orally once daily
  • Drug: Placebo to match ruxolitinib
    Placebo to match ruxolitinib tablets administered orally twice daily
Study Arms  ICMJE
  • Experimental: Momelotinib
    Participants will receive momelotinib plus placebo to match ruxolitinib.
    Interventions:
    • Drug: Momelotinib
    • Drug: Placebo to match ruxolitinib
  • Active Comparator: Ruxolitinib
    Participants will receive ruxolitinib plus placebo to match momelotinib.
    Interventions:
    • Drug: Ruxolitinib
    • Drug: Placebo to match momelotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2016)
432
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2013)
420
Actual Study Completion Date  ICMJE May 2, 2019
Actual Primary Completion Date September 12, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 < 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

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Czechia,   Denmark,   France,   Germany,   Hungary,   Israel,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Romania,   Singapore,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01969838
Other Study ID Numbers  ICMJE GS-US-352-0101
2013-002707-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sierra Oncology, Inc.
Study Sponsor  ICMJE Sierra Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Sierra Oncology, Inc.
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP