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Primary MyelofibrosisPhase 3Simplify 1NCT01969838

Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis

A Phase 3 study testing Momelotinib and Ruxolitinib in people with Primary Myelofibrosis and Post-Polycythemia Vera Myelofibrosis, run by Sierra Oncology LLC - a GSK company at 114 sites in 22 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Momelotinib and Ruxolitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
432 participants
Where
114 sitesin 22 countries
Study dates
6 Dec 2013to 2 May 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

114 sites in 22 countries.

114 sites in 22 countries

United States11 sites

  • Study site

    Atlanta, Georgia

  • Study site

    Baltimore, Maryland

  • Study site

    Boston, Massachusetts

  • Study site

    Chicago, Illinois

  • Study site

    Durham, North Carolina

  • Study site

    Escondido, California

  • Study site

    Jacksonville, Florida

  • Study site

    Phoenix, Arizona

  • Study site

    Seattle, Washington

  • Study site

    St Louis, Missouri

  • Study site

    Stanford, California

Other trials in United States

Australia10 sites

  • Study site

    Adelaide, South Australia

  • Study site

    Bedford Park, South Australia

  • Study site

    Brisbane, Queensland

  • Study site

    Darlinghurst, New South Wales

  • Study site

    Frankston, Victoria

  • Study site

    Herston, Queensland

  • Study site

    Melbourne, Victoria

  • Study site

    Parkville, New South Wales

  • Study site

    Perth, Western Australia

  • Study site

    Saint Leonards, New South Wales

Other trials in Australia

France10 sites

  • Study site

    Le Kremlin-Bicêtre

  • Study site

    Lens

  • Study site

    Lille

  • Study site

    Marseille

  • Study site

    Nantes

  • Study site

    Paris

  • Study site

    Pessac

  • Study site

    Pierre-Bénite, Auvergne-Rhône-Alpes

  • Study site

    Toulouse, Midi-pyrenees

  • Study site

    Villejuif

Other trials in France

Japan9 sites

  • Study site

    Bunkyo-ku, Tokyo

  • Study site

    Fukushima

  • Study site

    Kitaku Sapporo, Hokkaido

  • Study site

    Kumamoto

  • Study site

    Matsuyama

  • Study site

    Ōgaki, Gifu

  • Study site

    Okayama

  • Study site

    Osaka, Osaka

  • Study site

    Ōsaka-sayama, Osaka

Other trials in Japan

Poland9 sites

  • Study site

    Bialystok

  • Study site

    Brzozów

  • Study site

    Chorzów

  • Study site

    Gdansk, Pomeranian Voivodeship

  • Study site

    Krakow, Lesser Poland Voivodeship

  • Study site

    Lodz, Łódź Voivodeship

  • Study site

    Lublin, Lublin Voivodeship

  • Study site

    Poznan, Greater Poland Voivodeship

  • Study site

    Warsaw, Mazowiekie

Other trials in Poland

Germany8 sites

  • Study site

    Dresden

  • Study site

    Düsseldorf

  • Study site

    Freiburg im Breisgau

  • Study site

    Hamburg

  • Study site

    Leipzig, Saxony

  • Study site

    Mainz

  • Study site

    Mannheim

  • Study site

    München, Bavaria

Other trials in Germany

United Kingdom8 sites

  • Study site

    Cardiff, Wales

  • Study site

    Leicester, England

  • Study site

    London, England

  • Study site

    Manchester, England

  • Study site

    Newcastle upon Tyne, England

  • Study site

    Northern Ireland

  • Study site

    Nottingham

  • Study site

    Oxford, England

Other trials in United Kingdom

Spain6 sites

  • Study site

    Badalona

  • Study site

    Barcelona

  • Study site

    Majadahonda, Madrid

  • Study site

    Pamplona, Navarre

  • Study site

    Valencia

  • Study site

    Zaragoza

Other trials in Spain

Bulgaria5 sites

  • Study site

    Pleven

  • Study site

    Plovdiv

  • Study site

    Rousse

  • Study site

    Sofia

  • Study site

    Varna

Other trials in Bulgaria

Israel5 sites

  • Study site

    Afula

  • Study site

    Ashkelon

  • Study site

    Haifa

  • Study site

    Jerusalem

  • Study site

    Tel Aviv

Other trials in Israel

Romania5 sites

  • Study site

    Arad

  • Study site

    Brasov

  • Study site

    Bucharest

  • Study site

    Cluj-Napoca

  • Study site

    Iași

Other trials in Romania

Belgium4 sites

  • Study site

    Antwerp

  • Study site

    Charleroi, Hainaut

  • Study site

    Leuven

  • Study site

    Liège

Other trials in Belgium

Canada4 sites

  • Study site

    Edmonton, Alberta

  • Study site

    Hamilton, Ontario

  • Study site

    Toronto, Ontario

  • Study site

    Vancouver, British Columbia

Other trials in Canada

Netherlands4 sites

  • Study site

    Maastricht

  • Study site

    Nijmegen

  • Study site

    Rotterdam

  • Study site

    Utrecht

Other trials in Netherlands

Sweden4 sites

  • Study site

    Lund, Skåne County

  • Study site

    Örebro

  • Study site

    Stockholm

  • Study site

    Uddevalla

Other trials in Sweden

Czechia3 sites

  • Study site

    Brno

  • Study site

    Hradec Králové, Vychodocesky KRAJ

  • Study site

    Ostrava

Other trials in Czechia

Hungary3 sites

  • Study site

    Budapest

  • Study site

    Debrecen

  • Study site

    Kaposvár

Other trials in Hungary

Denmark2 sites

  • Study site

    Aalborg

  • Study site

    Herlev

Other trials in Denmark

Austria1 site

  • Study site

    Vienna, State of Vienna

Other trials in Austria

Singapore1 site

  • Study site

    Singapore

Other trials in Singapore

South Korea1 site

  • Study site

    Seoul

Other trials in South Korea

Taiwan1 site

  • Study site

    Kaohsiung City

Other trials in Taiwan

About this study

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)

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.

Being tested
Momelotinib, Ruxolitinib, Placebo to match momelotinib, Placebo to match ruxolitinib
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MomelotinibDrug

    Also called GS-0387, CYT387

    Momelotinib tablet administered orally once daily

  • RuxolitinibDrug

    Ruxolitinib tablets administered orally twice daily

  • Placebo to match momelotinibDrug

    Placebo to match momelotinib tablets administered orally once daily

  • Placebo to match ruxolitinibDrug

    Placebo to match ruxolitinib tablets administered orally twice daily

Study groups in NCT01969838
Study groupRoleWhat they receive
MomelotinibExperimentalParticipants will receive momelotinib plus placebo to match ruxolitinib.
Receives: Drug: Momelotinib; Drug: Placebo to match ruxolitinib
RuxolitinibActive comparatorParticipants will receive ruxolitinib plus placebo to match momelotinib.
Receives: Drug: Ruxolitinib; Drug: Placebo to match momelotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 24

Secondary outcomes (4)

  1. Total Symptom Score (TSS) Response Rate at Week 24

    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

    Measured: Week 24

  2. 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)

    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.

    Measured: Baseline to Week 24

  3. 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 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.

    Measured: Week 24

  4. 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)).

    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.

    Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2013 (estimated)
  2. Study start6 Dec 2013
  3. Primary completion12 Sep 2016
  4. Study completion2 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
432 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01969838
Sponsor's protocol ID
GS-US-352-0101
Other IDs
2013-002707-33
Acronym
Simplify 1
Status last verified
May 2023
First submitted
22 Oct 2013
Last updated
12 May 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Palandri F, O'Connell C, Vachhani P, McLornan DP, Koschmieder S, Hernandez-Boluda JC, Shimoda K, Zhang S, Ellis C, Lim J, Sahni J, Gupta V. Impact of Hemoglobin Improvement on Survival in Patients With Myelofibrosis and Anemia Treated With Momelotinib in the SIMPLIFY-1 and MOMENTUM Trials. Eur J Haematol. 2026 Jul 14. doi: 10.1111/ejh.70237. Online ahead of print.

    PubMed 42452788

  • Pemmaraju N, Lucchesi A, Oh ST, Wilson K, Hakimi Z, Buckley SA, Suthar P, Parkitny M, Wojciechowski P, Kolonko K, Mascarenhas JO. Efficacy of pacritinib versus momelotinib in patients with thrombocytopenic myelofibrosis: a matching-adjusted indirect treatment comparison. Expert Rev Hematol. 2026 Sep;19(9):1107-1115. doi: 10.1080/17474086.2026.2686813. Epub 2026 Jun 30.

    PubMed 42316774

  • Mesa R, Palmer JM, Palandri F, Masarova L, Harrison CN, Mazerolle F, M'hari M, Liu T, Zhang S, Cardellino A, Wang Z, Ellis CE, Patnaik D, Regnault A, LeBlanc TW. Association Between Transfusion Status, Hemoglobin Levels, and Patient-Reported Outcomes in Myelofibrosis: A Post Hoc Clinical Trial Analysis. Cancer Med. 2026 Apr;15(4):e71729. doi: 10.1002/cam4.71729.

    PubMed 41958363

  • 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.

    PubMed 40535755

  • 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.

    PubMed 39516087

  • Gupta V, Oh S, Devos T, Dubruille V, Catalano J, Somervaille TCP, Platzbecker U, Giraldo P, Kosugi H, Sacha T, Mayer J, Illes A, Ellis C, Wang Z, Gonzalez Carreras FJ, Strouse B, Mesa R. Momelotinib vs. ruxolitinib in myelofibrosis patient subgroups by baseline hemoglobin levels in the SIMPLIFY-1 trial. Leuk Lymphoma. 2024 Jul;65(7):965-977. doi: 10.1080/10428194.2024.2328800. Epub 2024 Mar 19.

    PubMed 38501751

  • 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.

    PubMed 37042865

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Momelotinib and Ruxolitinib in people with Primary Myelofibrosis and Post-Polycythemia Vera Myelofibrosis, run by Sierra Oncology LLC - a GSK company at 114 sites in 22 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 114 sites in United States, Australia, France, Japan, Poland and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Splenic Response Rate at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01969838, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2023; AzTrials last refreshed its copy on 8 Nov 2026.

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