Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis

NCT ID: NCT01969838

Last Updated: 2023-05-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

432 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-06

Study Completion Date

2019-05-02

Brief Summary

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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.

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Detailed Description

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Conditions

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Primary Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Momelotinib

Participants will receive momelotinib plus placebo to match ruxolitinib.

Group Type EXPERIMENTAL

Momelotinib

Intervention Type DRUG

Momelotinib tablet administered orally once daily

Placebo to match ruxolitinib

Intervention Type DRUG

Placebo to match ruxolitinib tablets administered orally twice daily

Ruxolitinib

Participants will receive ruxolitinib plus placebo to match momelotinib.

Group Type ACTIVE_COMPARATOR

Ruxolitinib

Intervention Type DRUG

Ruxolitinib tablets administered orally twice daily

Placebo to match momelotinib

Intervention Type DRUG

Placebo to match momelotinib tablets administered orally once daily

Interventions

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Momelotinib

Momelotinib tablet administered orally once daily

Intervention Type DRUG

Ruxolitinib

Ruxolitinib tablets administered orally twice daily

Intervention Type DRUG

Placebo to match momelotinib

Placebo to match momelotinib tablets administered orally once daily

Intervention Type DRUG

Placebo to match ruxolitinib

Placebo to match ruxolitinib tablets administered orally twice daily

Intervention Type DRUG

Other Intervention Names

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GS-0387 CYT387

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sierra Oncology LLC - a GSK company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Örebro, , Sweden

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Stockholm, , Sweden

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Uddevalla, , Sweden

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Kaohsiung City, , Taiwan

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Leicester, England, United Kingdom

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London, England, United Kingdom

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Manchester, England, United Kingdom

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Newcastle upon Tyne, England, United Kingdom

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Oxford, England, United Kingdom

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Cardiff, Wales, United Kingdom

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Northern Ireland, , United Kingdom

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Nottingham, , United Kingdom

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Phoenix, Arizona, United States

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Escondido, California, United States

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Stanford, California, United States

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Jacksonville, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Durham, North Carolina, United States

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Seattle, Washington, United States

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Darlinghurst, New South Wales, Australia

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Parkville, New South Wales, Australia

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Saint Leonards, New South Wales, Australia

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Brisbane, Queensland, Australia

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Herston, Queensland, Australia

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Adelaide, South Australia, Australia

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Bedford Park, South Australia, Australia

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Frankston, Victoria, Australia

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Melbourne, Victoria, Australia

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Perth, Western Australia, Australia

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Vienna, Vienna, Austria

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Charleroi, Hainaut, Belgium

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Antwerp, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Hradec Králové, Vychodocesky KRAJ, Czechia

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Brno, , Czechia

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Ostrava, , Czechia

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Aalborg, , Denmark

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Herlev, , Denmark

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Pierre-Bénite, Auvergne-Rhône-Alpes, France

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Toulouse, Midi-pyrenees, France

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Le Kremlin-Bicêtre, , France

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Lens, , France

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Lille, , France

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Marseille, , France

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Nantes, , France

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Paris, , France

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Pessac, , France

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Villejuif, , France

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München, Bavaria, Germany

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Leipzig, Saxony, Germany

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Dresden, , Germany

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Düsseldorf, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Kaposvár, , Hungary

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Afula, , Israel

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Ashkelon, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Tel Aviv, , Israel

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Ōgaki, Gifu, Japan

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Kitaku Sapporo, Hokkaido, Japan

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Osaka, Osaka, Japan

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Ōsaka-sayama, Osaka, Japan

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Bunkyo-ku, Tokyo, , Japan

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Fukushima, , Japan

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Kumamoto, , Japan

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Matsuyama, , Japan

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Okayama, , Japan

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Maastricht, , Netherlands

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Nijmegen, , Netherlands

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Rotterdam, , Netherlands

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Utrecht, , Netherlands

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Poznan, Greater Poland Voivodeship, Poland

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Krakow, Lesser Poland Voivodeship, Poland

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Lublin, Lublin Voivodeship, Poland

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Warsaw, Mazowiekie, Poland

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Gdansk, Pomeranian Voivodeship, Poland

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Bialystok, , Poland

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Brzozów, , Poland

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Chorzów, , Poland

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Lodz, Łódź Voivodeship, Poland

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Arad, , Romania

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Brasov, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Iași, , Romania

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Singapore, , Singapore

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Seoul, , South Korea

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Majadahonda, Madrid, Spain

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Pamplona, Navarre, Spain

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Badalona, , Spain

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Barcelona, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Lund, Skåne County, Sweden

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Countries

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United States Australia Austria Belgium Bulgaria Canada Czechia Denmark France Germany Hungary Israel Japan Netherlands Poland Romania Singapore South Korea Spain Sweden Taiwan United Kingdom

References

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Mesa RA, Talpaz M, Mazerolle F, Gorsh B, M'Hari M, Regnault A, Ellis C, Wang Z, Purser M, Liu T, Strouse B, Patnaik D. Time Without Transfusion Reliance (TWiTR): Integrating Survival Quality Into Myelofibrosis Treatment Strategies Based on the Phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM Trials. EJHaem. 2025 Jun 18;6(3):e70075. doi: 10.1002/jha2.70075. eCollection 2025 Jun.

Reference Type DERIVED
PMID: 40535755 (View on PubMed)

Harrison CN, Mesa R, Talpaz M, Gupta V, Gerds AT, Perkins A, Goh YT, Fox ML, McLornan D, Palmer J, Foltz L, Vannucchi A, Koschmieder S, Passamonti F, Lee SE, Ellis C, Strouse B, Gonzalez Carreras FJ, Oh ST. Longitudinal Assessment of Transfusion Intensity in Patients With JAK Inhibitor-Naive or -Experienced Myelofibrosis Treated With Momelotinib. Clin Lymphoma Myeloma Leuk. 2025 Mar;25(3):199-211. doi: 10.1016/j.clml.2024.10.001. Epub 2024 Oct 16.

Reference Type DERIVED
PMID: 39516087 (View on PubMed)

Verstovsek S, Mesa R, Gupta V, Lavie D, Dubruille V, Cambier N, Platzbecker U, Hus M, Xicoy B, Oh ST, Kiladjian JJ, Vannucchi AM, Gerds A, Egyed M, Mayer J, Sacha T, Kawashima J, Morris M, Huang M, Harrison C. Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials. Blood Adv. 2023 Jul 25;7(14):3582-3591. doi: 10.1182/bloodadvances.2022009311.

Reference Type DERIVED
PMID: 37042865 (View on PubMed)

Other Identifiers

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2013-002707-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-352-0101

Identifier Type: -

Identifier Source: org_study_id

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