Simplify 1: Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis

Sponsor
Sierra Oncology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01969838
Collaborator
(none)
432
114
2
64.8
3.8
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
432 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, 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)
Actual Study Start Date :
Dec 6, 2013
Actual Primary Completion Date :
Sep 12, 2016
Actual Study Completion Date :
May 2, 2019

Arms and Interventions

Arm Intervention/Treatment
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

    Outcome Measures

    Primary Outcome Measures

    1. Splenic response rate at Week 24 [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.

    Secondary Outcome Measures

    1. Response rate in total symptom score at Week 24 [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.

    2. Rate of red blood cell (RBC) transfusion through Week 24 [Baseline to Week 24]

      Rate of RBC transfusion is defined as the average number of RBC units per participant per month.

    3. RBC transfusion independence rate at Week 24 [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.

    4. RBC transfusion dependence rate at Week 24 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 109/L (≥ 100 x 109/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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Arizona United States
    2 Escondido California United States
    3 Stanford California United States
    4 Jacksonville Florida United States
    5 Atlanta Georgia United States
    6 Chicago Illinois United States
    7 Baltimore Maryland United States
    8 Boston Massachusetts United States
    9 Saint Louis Missouri United States
    10 Durham North Carolina United States
    11 Seattle Washington United States
    12 Darlinghurst New South Wales Australia
    13 Parkville New South Wales Australia
    14 Saint Leonards New South Wales Australia
    15 Brisbane Queensland Australia
    16 Herston Queensland Australia
    17 Adelaide South Australia Australia
    18 Bedford Park South Australia Australia
    19 Frankston Victoria Australia
    20 Melbourne Victoria Australia
    21 Perth Western Australia Australia
    22 Wien Vienna Austria
    23 Charleroi Hainaut Belgium
    24 Antwerp Belgium
    25 Leuven Belgium
    26 Liege Belgium
    27 Pleven Bulgaria
    28 Plovdiv Bulgaria
    29 Ruse Bulgaria
    30 Sofia Bulgaria
    31 Varna Bulgaria
    32 Edmonton Alberta Canada
    33 Vancouver British Columbia Canada
    34 Hamilton Ontario Canada
    35 Toronto Ontario Canada
    36 Hradec Kralove Vychodocesky KRAJ Czechia
    37 Brno Czechia
    38 Ostrava Czechia
    39 Aalborg Denmark
    40 Herlev Denmark
    41 Toulouse cedex 9 Midi-pyrenees France
    42 Pierre Bénite Cedex Rhone-alpes France
    43 Le Kremlin Bicetre Cedex France
    44 Lens France
    45 Lille Cedex France
    46 Marseille Cedex 9 France
    47 Nantes cedex 1 France
    48 Paris France
    49 Pessac Cedex France
    50 Villejuif Cedex France
    51 München Bayern Germany
    52 Leipzig Sachsen Germany
    53 Dresden Germany
    54 Dusseldorf Germany
    55 Freiburg Germany
    56 Hamburg Germany
    57 Mainz Germany
    58 Mannheim Germany
    59 Budapest Hungary
    60 Debrecen Hungary
    61 Kaposvár Hungary
    62 Afula Israel
    63 Ashkelon Israel
    64 Haifa Israel
    65 Jerusalem Israel
    66 Tel Aviv Israel
    67 Ogaki City Gifu Japan
    68 Kitaku Sapporo Hokkaido Japan
    69 Osaka Sayama Osaka Japan
    70 Osaka-City Osaka Japan
    71 Bunkyo-ku, Tokyo Japan
    72 Fukushima City Japan
    73 Kumamoto City Japan
    74 Matsuyama Japan
    75 Okayama Japan
    76 Seoul Korea, Republic of
    77 Maastricht Netherlands
    78 Nijmegen Netherlands
    79 Rotterdam Netherlands
    80 Utrecht Netherlands
    81 Lodz Lodzkie Poland
    82 Lublin Lubelskie Poland
    83 Kraków Malopolskie Poland
    84 Warszawa Mazowiekie Poland
    85 Gdansk Pomorskie Poland
    86 Poznan Wielkopolskie Poland
    87 Bialystok Poland
    88 Brzozow Poland
    89 Chorzow Poland
    90 Arad Romania
    91 Brasov Romania
    92 Bucuresti Romania
    93 Cluj-Napoca Romania
    94 Iasi Romania
    95 Singapore Singapore
    96 Majadahonda Madrid Spain
    97 Pamplona Navarra Spain
    98 Badalona Spain
    99 Barcelona Spain
    100 Valencia Spain
    101 Zaragoza Spain
    102 Lund Skane Sweden
    103 Stockholm Sweden
    104 Uddevalla Sweden
    105 Örebro Sweden
    106 Kaohsiung Taiwan
    107 Leicester England United Kingdom
    108 London England United Kingdom
    109 Manchester England United Kingdom
    110 Newcastle Upon Tyne England United Kingdom
    111 Oxford England United Kingdom
    112 Cardiff Wales United Kingdom
    113 Northern Ireland United Kingdom
    114 Nottingham United Kingdom

    Sponsors and Collaborators

    • Sierra Oncology, Inc.

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sierra Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT01969838
    Other Study ID Numbers:
    • GS-US-352-0101
    • 2013-002707-33
    First Posted:
    Oct 25, 2013
    Last Update Posted:
    Apr 15, 2020
    Last Verified:
    Apr 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 15, 2020