Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis

NCT01969838 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-352-01012013-002707-33
• Study Type: interventional
• Target: 432
• Locations: 21 countries
• Sites: 113

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Splenic Response Rate at Week 24

  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.

  Week 24

Secondary Outcomes (4)

• Total Symptom Score (TSS) Response Rate at Week 24

  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)

  Baseline to Week 24

• 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)

  Week 24

• 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)).

  Week 24

Study Arms (2)

Momelotinib

EXPERIMENTAL

Participants will receive momelotinib plus placebo to match ruxolitinib.

Drug: Momelotinib; Drug: Placebo to match ruxolitinib

Ruxolitinib

ACTIVE COMPARATOR

Participants will receive ruxolitinib plus placebo to match momelotinib.

Drug: Ruxolitinib; Drug: Placebo to match momelotinib

Interventions

Momelotinib DRUG

Momelotinib tablet administered orally once daily

Also known as: GS-0387, CYT387

Momelotinib

Ruxolitinib DRUG

Ruxolitinib tablets administered orally twice daily

Ruxolitinib

Placebo to match momelotinib DRUG

Placebo to match momelotinib tablets administered orally once daily

Ruxolitinib

Placebo to match ruxolitinib DRUG

Placebo to match ruxolitinib tablets administered orally twice daily

Momelotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (114)

Unknown Facility

Phoenix, Arizona, United States

Location

Unknown Facility

Escondido, California, United States

Location

Unknown Facility

Stanford, California, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Darlinghurst, New South Wales, Australia

Location

Unknown Facility

Parkville, New South Wales, Australia

Location

Unknown Facility

Saint Leonards, New South Wales, Australia

Location

Unknown Facility

Brisbane, Queensland, Australia

Location

Unknown Facility

Herston, Queensland, Australia

Location

Unknown Facility

Adelaide, South Australia, Australia

Location

Unknown Facility

Bedford Park, South Australia, Australia

Location

Unknown Facility

Frankston, Victoria, Australia

Location

Unknown Facility

Melbourne, Victoria, Australia

Location

Unknown Facility

Perth, Western Australia, Australia

Location

Unknown Facility

Vienna, Vienna, Austria

Location

Unknown Facility

Charleroi, Hainaut, Belgium

Location

Unknown Facility

Antwerp, Belgium

Location

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Liège, Belgium

Location

Unknown Facility

Pleven, Bulgaria

Location

Unknown Facility

Plovdiv, Bulgaria

Location

Unknown Facility

Rousse, Bulgaria

Location

Unknown Facility

Sofia, Bulgaria

Location

Unknown Facility

Varna, Bulgaria

Location

Unknown Facility

Edmonton, Alberta, Canada

Location

Unknown Facility

Vancouver, British Columbia, Canada

Location

Unknown Facility

Hamilton, Ontario, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

Hradec Králové, Vychodocesky KRAJ, Czechia

Location

Unknown Facility

Brno, Czechia

Location

Unknown Facility

Ostrava, Czechia

Location

Unknown Facility

Aalborg, Denmark

Location

Unknown Facility

Herlev, Denmark

Location

Unknown Facility

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Location

Unknown Facility

Toulouse, Midi-pyrenees, France

Location

Unknown Facility

Le Kremlin-Bicêtre, France

Location

Unknown Facility

Lens, France

Location

Unknown Facility

Lille, France

Location

Unknown Facility

Marseille, France

Location

Unknown Facility

Nantes, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Pessac, France

Location

Unknown Facility

Villejuif, France

Location

Unknown Facility

München, Bavaria, Germany

Location

Unknown Facility

Leipzig, Saxony, Germany

Location

Unknown Facility

Dresden, Germany

Location

Unknown Facility

Düsseldorf, Germany

Location

Unknown Facility

Freiburg im Breisgau, Germany

Location

Unknown Facility

Hamburg, Germany

Location

Unknown Facility

Mainz, Germany

Location

Unknown Facility

Mannheim, Germany

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Debrecen, Hungary

Location

Unknown Facility

Kaposvár, Hungary

Location

Unknown Facility

Afula, Israel

Location

Unknown Facility

Ashkelon, Israel

Location

Unknown Facility

Haifa, Israel

Location

Unknown Facility

Jerusalem, Israel

Location

Unknown Facility

Tel Aviv, Israel

Location

Unknown Facility

Ōgaki, Gifu, Japan

Location

Unknown Facility

Kitaku Sapporo, Hokkaido, Japan

Location

Unknown Facility

Osaka, Osaka, Japan

Location

Unknown Facility

Ōsaka-sayama, Osaka, Japan

Location

Unknown Facility

Bunkyo-ku, Tokyo, Japan

Location

Unknown Facility

Fukushima, Japan

Location

Unknown Facility

Kumamoto, Japan

Location

Unknown Facility

Matsuyama, Japan

Location

Unknown Facility

Okayama, Japan

Location

Unknown Facility

Maastricht, Netherlands

Location

Unknown Facility

Nijmegen, Netherlands

Location

Unknown Facility

Rotterdam, Netherlands

Location

Unknown Facility

Utrecht, Netherlands

Location

Unknown Facility

Poznan, Greater Poland Voivodeship, Poland

Location

Unknown Facility

Krakow, Lesser Poland Voivodeship, Poland

Location

Unknown Facility

Lublin, Lublin Voivodeship, Poland

Location

Unknown Facility

Warsaw, Mazowiekie, Poland

Location

Unknown Facility

Gdansk, Pomeranian Voivodeship, Poland

Location

Unknown Facility

Bialystok, Poland

Location

Unknown Facility

Brzozów, Poland

Location

Unknown Facility

Chorzów, Poland

Location

Unknown Facility

Lodz, Łódź Voivodeship, Poland

Location

Unknown Facility

Arad, Romania

Location

Unknown Facility

Brasov, Romania

Location

Unknown Facility

Bucharest, Romania

Location

Unknown Facility

Cluj-Napoca, Romania

Location

Unknown Facility

Iași, Romania

Location

Unknown Facility

Singapore, Singapore

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

Majadahonda, Madrid, Spain

Location

Unknown Facility

Pamplona, Navarre, Spain

Location

Unknown Facility

Badalona, Spain

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Valencia, Spain

Location

Unknown Facility

Zaragoza, Spain

Location

Unknown Facility

Lund, Skåne County, Sweden

Location

Unknown Facility

Örebro, Sweden

Location

Unknown Facility

Stockholm, Sweden

Location

Unknown Facility

Uddevalla, Sweden

Location

Unknown Facility

Kaohsiung City, Taiwan

Location

Unknown Facility

Leicester, England, United Kingdom

Location

Unknown Facility

London, England, United Kingdom

Location

Unknown Facility

Manchester, England, United Kingdom

Location

Unknown Facility

Newcastle upon Tyne, England, United Kingdom

Location

Unknown Facility

Oxford, England, United Kingdom

Location

Unknown Facility

Cardiff, Wales, United Kingdom

Location

Unknown Facility

Northern Ireland, United Kingdom

Location

Unknown Facility

Nottingham, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 40535755 DERIVED

• 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.

  PMID: 39516087 DERIVED

• 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.

  PMID: 37042865 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

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

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: Sierra Oncology, a GlaxoSmithKline company

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 25, 2013
• Study Start: December 6, 2013
• Primary Completion: September 12, 2016
• Study Completion: May 2, 2019
• Last Updated: May 12, 2023
• Results First Posted: May 12, 2023

Record last verified: 2023-05

Locations

IL (5); RO (5); DK (2); HU (3); NL (4); DE (8); GB (8); CZ (3); TW (1); SE (4); BE (4); PL (9); FR (10); SG (1); AU (10); ES (6); US (11); KR (1); CA (4); JP (9); BU (5)