A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)

• ClinicalTrials.gov Identifier: NCT04173494
• Recruitment Status: Completed
• First Posted: November 22, 2019
• Results First Posted: December 22, 2022
• Last Update Posted: November 1, 2023
• Sponsor: Sierra Oncology LLC - a GSK company
• Information provided by (Responsible Party): Sierra Oncology LLC - a GSK company

Study Description

Brief Summary:

MOMENTUM is a randomized, double-blind, active control Phase 3 trial intended to confirm the differentiated clinical benefits of the investigational drug momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic participants who have previously received an approved Janus kinase inhibitor (JAKi) therapy for myelofibrosis (MF). The purpose of this clinical study is to compare the effectiveness and safety of MMB to DAN in treating and reducing: 1) disease related symptoms, 2) the need for blood transfusions and 3) splenomegaly, in adults with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The study is planned in countries including, but not limited to: Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Romania, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom (UK) and United States (US).

Participants must be symptomatic with a Myelofibrosis Symptom Assessment Form (MFSAF) version (v) 4.0 Total Symptom Score of >= 10 at screening, and be anemic with hemoglobin (Hgb) < 10 gram/deciliter (g/dL). For participants with ongoing JAKi therapy at screening, JAKi therapy must be tapered over a period of at least 1 week, followed by a 2-week non-treatment washout interval prior to randomization.

Participants will be randomized 2:1 to orally self-administer blinded treatment: MMB plus placebo or DAN plus placebo. Participants randomized to receive MMB who complete the randomized treatment period to the end of Week 24 may continue to receive MMB in the open-label extended treatment period to the end of Week 204 (a total period of treatment of approximately 4 years) if the participants tolerates and continues to benefit from MMB.

Participants randomized to receive DAN may cross-over to MMB open-label treatment in the following circumstances: at the end of Week 24 if they complete the randomized treatment period; or at the end of Week 24 if they discontinue treatment with DAN but continue study assessments and do not receive prohibited medications including alternative active anti-MF therapy; or at any time during the randomized treatment period if they meet the protocol-defined criteria for radiographically confirmed symptomatic splenic progression. Participants randomized to receive DAN who are receiving clinical benefit at the end of Week 24 may choose to continue DAN therapy up to Week 48. The comparator treatment, DAN, is an approved medication in the US and in some other countries and is recommended by national guidelines as a treatment for anemia in MF.

Condition or disease	Intervention/treatment	Phase
Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis	Drug: Momelotinib; Drug: Placebo to match danazol; Drug: Danazol; Drug: Placebo to match momelotinib	Phase 3

Detailed Description:

MOMENTUM Contact Email: GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 195 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: During the 24 week randomized treatment phase of the study, participants, investigators and sponsor and relevant vendor personnel (with the exception of specified unblinded personnel, for example clinical supply) will remain blinded to the participant's treatment assignment and to aggregate data that may lead to inadvertent unblinding. Participants who continue treatment with momelotinib or danazol after Week 24 in the extended treatment phase will receive unblinded treatment.
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Phase 3 Study to Evaluate the Activity of Momelotinib (MMB) Versus Danazol (DAN) in Symptomatic, Anemic Subjects With Primary Myelofibrosis (PMF), Post-polycythemia Vera (PV) Myelofibrosis, or Post-essential Thrombocythemia (ET) Myelofibrosis Who Were Previously Treated With JAK Inhibitor Therapy
• Actual Study Start Date: February 7, 2020
• Actual Primary Completion Date: December 3, 2021
• Actual Study Completion Date: December 29, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Momelotinib; Participants will receive momelotinib plus placebo to match danazol	Drug: Momelotinib; Momelotinib tablets will be self-administered orally once daily; Other Name: MMB, GS-0387, CYT387; Drug: Placebo to match danazol; Danazol placebo capsules will be self-administered orally twice daily
Active Comparator: Danazol; Participants will receive danazol plus placebo to match momelotinib	Drug: Danazol; Danazol capsules will be self-administered orally twice daily; Other Name: Danocrine; Drug: Placebo to match momelotinib; Momelotinib placebo tablets will be self-administered orally once daily

Outcome Measures

Primary Outcome Measures :

1. Total Symptom Score (TSS) Response Rate at Week 24 [ Time Frame: Baseline and Week 24 ]
   Myelofibrosis Symptom Assessment Form (MFSAF) TSS version (v) 4.0 response rate was defined as percentage of participants with a >= 50 percent (%) reduction from Baseline in mean MFSAF TSS over consecutive 28-day period immediately before end of Week 24. TSS response rate was measured using MFSAF v4.0. MFSAF v4.0 comprises 7 domains representing 7 most relevant symptoms of myelofibrosis (MF) identified through existing participant and clinician-based evidence: fatigue,night sweats,pruritus,abdominal discomfort,pain under left ribs,early satietyand bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0(absent) to 10(worst imaginable). The MFSAF TSS was calculated as sum of scores of 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date.

Secondary Outcome Measures :

1. Percentage of Participants With Transfusion Independence (TI) at Week 24 [ Time Frame: Week 24 ]
   TI status was defined as not receiving red blood cell (RBC) or whole blood transfusion for >=12 weeks, with no hemoglobin (Hgb) level < 8 grams per deciliter (g/dL) during the same interval. Percentage of participants with TI have been presented.
2. Splenic Response Rate (SRR) of >=25% at Week 24 [ Time Frame: Baseline and Week 24 ]
   Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of >=25% from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
3. Change From Baseline in MFSAF TSS at Week 24 [ Time Frame: Baseline and Week 24 ]
   TSS was measured using the MFSAF v4.0. The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). The MFSAF TSS was calculated as the sum of scores of the 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
4. Splenic Response Rate (SRR) of >= 35% at Week 24 [ Time Frame: Baseline and Week 24 ]
   Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of >=35 % from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
5. Percentage of Participants With Zero RBC Units Transfused Over 24-Weeks [ Time Frame: Up to 24 weeks ]
   Percentage of participants with zero RBC units transfused over 24-weeks were reported.
6. Percentage of Participants With <=4 RBC Units Transfused Over 24-weeks [ Time Frame: Up to 24 weeks ]
   Percentage of participants with <=4 RBC units transfused over 24-weeks were reported.
7. Duration of MFSAF TSS Response [ Time Frame: Up to a maximum of 151 weeks ]
   Duration of MFSAF TSS response is defined as the number of days from the start of the initial 28-day period in which a participant had a >= 50% reduction from Baseline TSS to the first day of the 7-day assessment that determines the mean TSS for the 28-day period during which the participants TSS equals or exceeds their Baseline value.
8. Duration of TI Response [ Time Frame: Up to a maximum of 151 weeks ]
   Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level < 8 g/dL (except in the case of clinically overt bleeding).
9. Mean Cumulative Number of Whole Blood Units Transfused Over 24 Weeks [ Time Frame: Up to Week 24 ]
   Cumulative transfusion risk was calculated as the estimated mean cumulative number of whole blood units transfused during the study.
10. Percentage of Participants With Transfusion Dependence (TD) Status at Week 24 [ Time Frame: Week 24 ]
    TD status at Week 24 is defined as requirement of >=4 RBC units in an 8-week period immediately prior to the end of Week 24.
11. Percentage of Participants With a Hemoglobin Response [ Time Frame: Baseline and Week 24 ]
    Hemoglobin responses are defined as increases of >= 1, >= 1.5, or >= 2 g/dL from Baseline in Hgb, as measured over a (rolling) period of at least 12 consecutive weeks falling entirely before the end of Week 24. Baseline was the last assessment done before or on the day of first dose date. Data has been reported for percentage of participants who had >= 1, >= 1.5, or >= 2 g/dL increase from Baseline in hemoglobin.
12. Number of Baseline TD Participants With TI Status at Week 24 [ Time Frame: Week 24 ]
    Participants were defined as having TD if they met both of the following requirements in the 8 weeks immediately before the end of Week 24: >= 4 red blood cell or whole blood units were transfused (except in the case of clinically overt bleeding), each in response to a hemoglobin assessment of <= 9.5 g/dL; and there were >= 2 hemoglobin assessments with >= 28 days between the earliest and latest hemoglobin assessments. TI status was defined as not requiring red blood cell transfusion (except in the case of clinically overt bleeding) for >= 12 weeks immediately prior to the end of Week 24, with hemoglobin levels >= 8 g/dL.
13. Duration of TI in Baseline TD Participants [ Time Frame: Up to a maximum of 151 weeks ]
    Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level < 8 g/dL (except in the case of clinically overt bleeding).
14. Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- up to Week 24 [ Time Frame: Up to Week 24 ]
    An adverse event (AE) is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
15. Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- From Week 24 to a Maximum of 151 Weeks [ Time Frame: From Week 24 to a maximum of 151 weeks ]
    An AE is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
16. Overall Survival (OS) [ Time Frame: Up to a maximum of 151 weeks ]
    Overall survival is defined as the interval from the first study drug dosing date (or randomization date for participants who did not receive treatment) to death from any cause.
17. Leukemia-free Survival (LFS) [ Time Frame: Up to a maximum of 151 weeks ]
    LFS is defined as the interval from first study drug dosing date (or randomization date for participants who did not receive treatment) to any evidence of leukemic transformation and/or death (from any cause).
18. Change From Baseline in Disease-related Fatigue as Assessed by MFSAF TSS v4.0 at Week 24 [ Time Frame: Baseline and Week 24 ]
    The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant- and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). Data has been reported for Disease-related Fatigue domain measured using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable), higher score indicates worst outcome. An increase in score from Baseline indicated a worsening of fatigue and a decrease in score from Baseline indicated an improvement in fatigue. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
19. Change From Baseline in Cancer-related Fatigue as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The EORTC QLQ-C30 is comprised of 5 functional scales (physical, role, emotional, social, cognitive), eight single item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea), as well as sub-scales assessing global health/quality of life and financial impact. Most items use a 4-point Likert scale from "not at all" to "very much" and a one-week recall period with the exception of the final two items which use a 7 point scale response from "very poor" to "excellent". Scores were averaged and transformed to a 0-100 scale, with higher scores representing better functioning/quality of life. An increase in scores from Baseline indicated an improved functioning/quality of life, and a decrease in scores from Baseline indicated a worsened functioning/quality of life. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
20. Change From Baseline in Physical Function Score as Assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b at Week 24 [ Time Frame: Baseline and Week 24 ]
    PROMIS Physical Function Short Form 10b consists of 14 questions; each with a 5-point response. PROMIS short form assesses self-reported capability of a participant rather than actual performance of physical activities. This includes functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back) as well as instrumental activities of daily living, such as running errands. Participants scored each response on a scale from 1 (unable to do) to 5 (without any difficulty, or not at all). Total possible range of scores was 14 to 70, with higher scores corresponding to a greater physical function ability. An increase in score from Baseline indicated an improvement in physical function ability and a decrease in score from Baseline indicated a reduction in physical function ability. Baseline was last assessment done before or on the day of first dose date. Change from Baseline was defined as post-Baseline value minus Baseline value.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age >= 18 years.
• Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post- polycythemia vera/essential thrombocythemia (PV/ET) MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT criteria).
• Symptomatic, defined as a TSS of >= 10 units assessed by a single MFSAF v4.0 assessment during Screening prior to Baseline period (Day BL1).
• Anemic, defined as a Hgb < 10 g/dL in Screening/Baseline period.
• Previously treated with an approved JAK inhibitor for PMF or Post-PV/ET MF for >= 90 days, or >= 28 days if JAK inhibitor therapy is complicated by RBC transfusion requirement of >= 4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma.
• Baseline splenomegaly, defined as having a palpable spleen at >= 5 centimeter (cm), below the left costal margin, or with volume >= 450 cubic centimeter (cm^3) on imaging (ultrasound, magnetic resonance imaging [MRI] or computed tomography [CT] are acceptable), assessed during Screening at any point prior to Randomization.
• High risk, intermediate-2, or intermediate-1 risk MF as defined by Dynamic International Prognostic Scoring System (DIPSS), or DIPSS-plus.
• No allogeneic stem cell transplant planned.

• Acceptable laboratory assessments:

  1. Absolute neutrophil count (ANC) >= 0.75 × 10^9/Liter (L).
  2. Platelet count (PLT) >= 25 × 10^9/L (without requirement for platelet transfusion).
  3. Peripheral blast count < 10%.
  4. Alanine aminotransferase/ glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT) <= 3 × Upper Limit Normal (ULN) (<= 5 × 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).
  5. Calculated creatinine clearance (CCr) >= 30 milliliter per minute (mL/min) according to Cockcroft-Gault.
  6. Direct bilirubin <= 2.0 × ULN.

Exclusion Criteria:

• Use of the following treatments within the time periods noted:

  1. Prior momelotinib treatment at any time.
  2. Approved JAK inhibitor therapy (eg, fedratinib or ruxolitinib) within 1 week prior to the first day of Baseline.
  3. Active anti-MF therapy within 1 week prior to the first day of Baseline.
  4. Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization.
  5. Investigational agent (including investigational JAK inhibitors) within 4 weeks prior to Randomization.
  6. Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization.
  7. Danazol within 3 months prior to Randomization.
  8. Splenic irradiation within 3 months prior to Randomization.
  9. Current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin.
• History of prostate cancer, with the exception of localized prostate cancer that has been treated surgically or by radiotherapy with curative intent and presumed cured.
• Prostate specific antigen (PSA) > 4 nanograms per milliliter (ng/mL).
• Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI scan or CT scan for spleen volume measurement per protocol requirements.

• Any of the following (criteria a - k):

  1. Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial).
  2. Significant active or chronic bleeding event >= Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization.
  3. Unstable angina pectoris within 6 months prior to Randomization.
  4. Symptomatic congestive heart failure within 6 months prior to Randomization.
  5. Uncontrolled cardiac arrhythmia within 6 months prior to Randomization.
  6. QT Interval Corrected Using Fridericia's Formula (QTcF) interval > 500 millisecond (msec), unless attributed to bundle branch block.
  7. Current progressive thrombosis despite treatment.
  8. History of porphyria.
  9. Child-Pugh score >= 10.
  10. Psychiatric illness, social situation, or any other condition that would limit compliance with trial requirements or may interfere with the interpretation of study results, as judged by investigator or sponsor.
  11. Inability or unwillingness to comply with the protocol restrictions on MF therapy and other medications prior to and during study treatment.
• Participants with a prior or concurrent malignancy, whose natural history or treatment has a significant potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding or thalassemia.
• Known positive status for human immunodeficiency viruses (HIV).
• Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier (testing required for hepatitis B and C).
• Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per CTCAE v5.0.
• Presence of peripheral neuropathy >= Grade 2 per CTCAE v5.0.
• Women who are already pregnant or lactating. Additional inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Hospital - Phoenix

Phoenix, Arizona, United States, 85054

United States, California

Irvine Center for Clinical Research

Irvine, California, United States, 92614

Norris Comprehensive Cancer Center

Los Angeles, California, United States, 91011

American Institute of Research - Whittier

Whittier, California, United States, 90603

United States, Colorado

University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, United States, 80045

United States, District of Columbia

Georgetown University Medical Center

Washington, District of Columbia, United States, 20057

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Illinois

Northwest Oncology & Hematology - Rolling Meadows

Rolling Meadows, Illinois, United States, 60008

United States, Missouri

Washington University School of Medicine in Saint Louis

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Columbia University Irving Medical Center - Presbyterian Hospital

New York, New York, United States, 10032

United States, Ohio

Cleveland Clinic - Richard E. Jacobs Health Center

Avon, Ohio, United States, 44011

Gabrail Cancer Center

Canton, Ohio, United States, 44718

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Allegheny Health Network

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229

Australia, Australian Capital Territory

Canberra Region Cancer Centre

Garran, Australian Capital Territory, Australia, 2605

Australia, New South Wales

Calvary Mater Newcastle Hospital

Waratah, New South Wales, Australia, 2298

Australia, South Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia, 5042

Australia, Victoria

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Australia, Western Australia

Perth Radiological Clinic - Magnetic Resonance Centre

Perth, Western Australia, Australia, 6000

Austria

Medizinische Universität Innsbruck

Innsbruck, Tyrol, Austria, 6020

Ordensklinikum Linz Elisabethinen

Linz, Upper Austria, Austria, 4020

Medizinische Universität Wien

Wien, Vienna, Austria, 1090

Oberösterreichische Gesundheitsholding GmbH

Steyr, Austria, 4400

Belgium

Hôpital Erasme

Bruxelles, Brussels, Belgium, 1070

Grand Hôpital de Charleroi - Notre Dame

Charleroi, Hainaut, Belgium, 6000

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan

Brugge, West-Vlaanderen, Belgium, 8000

Ziekenhuis Netwerk Antwerpen Stuivenberg

Antwerpen, Belgium, 2060

Centre Hospitalier Universitaire de Liège

Liège, Belgium, B-4000

Bulgaria

University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD

Pleven, Bulgaria, 5800

University Hospital St. Ivan Rilski

Sofia, Bulgaria, 1431

University Multiprofile Hospital For Active Treatment Aleksandrovska

Sofia, Bulgaria, 1431

National Specialized Hospital for Active Treatment of Haematologic Diseases

Sofia, Bulgaria, 1756

Canada, British Columbia

Saint Paul's Hospital

Vancouver, British Columbia, Canada, V6Z 1Y6

Canada, Nova Scotia

Queen Elizabeth II Health Sciences Centre - Halifax Infirmary

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

McMaster University Medical Center

Hamilton, Ontario, Canada, L8V 5C2

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Research Institute of the McGill University Health Centre

Montréal, Quebec, Canada, H3H 2R9

Canada

Hôpital de l'Enfant-Jésus

Québec, Canada, G1J 1Z4

Czechia

Fakultni Nemocnice Brno

Brno, Jihormoravsky Kraj, Czechia, 625 00

Denmark

Herlev Hospital

Herlev, Hovedstaden, Denmark, 2730

Aalborg Universitetshospital - Syd

Aalborg, Nordjylland, Denmark, 9000

Sjællands Universitetshospital - Roskilde

Roskilde, Sjælland, Denmark, 4000

Odense Universitetshospital

Odense, Syddanmark, Denmark, 5000

France

Hôpital Haut-Lévêque

Pessac, Aquitaine, France, 33604

Hospital Center University Of Caen Normandie

Caen, Basse-Normandie, France, 14033

Hôpital Claude Huriez

Lille, Hauts-de-France, France, 59037

Hôpital Saint-Louis

Paris, Ile-de-France, France, 75010

Hôpital Saint-Antoine

Paris, Ile-de-France, France, 75571

Centre Hospitalier Universitaire Limoges

Limoges, Limousin, France, 87042

Centre Hospitalier De Lens

Lens, Nord Pas-Des-Calais, France, 62307

Centre Hospitalier Le Mans

Le Mans, Pays De La Loire, France, 72037

Centre Hospitalier Universitaire Amiens-Picardie - Site Sud

Amiens, Picardie, France, 80054

Hôpital l'Archet

Nice, Provence-Alpes-Côte d'Azur, France, 06200

Centre Hospitalier Lyon-Sud

Pierre-Bénite, Rhone-Alps, France, 69495

Centre Hosptitalier Universitaire Angers

Angers, France, 49 933

Hôpital Saint-Vincent De Paul - Lille

Lille, France, 59000

Hôpital De La Conception

Marseille, France, 13385

Hôpital Emile Muller

Mulhouse, France, 68100

Centre Hospitalier Universitaire Nantes - Hôtel Dieu

Nantes, France, 44000

Centre Hospitalier Universitaire de Poitiers

Poitiers, France, 86021

Germany

Universitätsklinikum Aachen

Aachen, Nordrhein-Westfalen, Germany, 52074

Universitätsklinikum Essen

Essen, Nordrhein-Westfalen, Germany, 45147

Johannes Wesling Klinikum Minden

Minden, Nordrhein-Westfalen, Germany, 32429

Universitätsklinikum Halle

Halle, Sachsen-Anhalt, Germany, 06120

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Sachsen, Germany, 01307

Universitätsklinikum Leipzig

Leipzig, Sachsen, Germany, 04103

Universitätsklinikum Jena

Jena, Thuringen, Germany, 07747

Uniklinik Köln

Köln, Germany, 50937

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, Germany, 23538

Kliniken Ostalb - Stauferklinikum Schwäbisch Gmünd

Mutlangen, Germany, 73557

Hungary

Pécsi Tudományegyetem Klinikai Központ

Pécs, Baranya, Hungary, 7624

Debreceni Egyetem Klinikai Központ

Debrecen, Hajdu-Bihar, Hungary, 4032

Szent Borbála Kórház

Tatabánya, Komárom-Esztergom, Hungary, 2800

Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet - Szent László Telephely

Budapest, Pest, Hungary, 1097

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, Somogy, Hungary, 7400

Szabolcs-Szatmár-Bereg Megyei Kórházak És Egyetemi Oktatókórház

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400

Markusovszky Egyetemi Oktatókórház Szombathely

Szombathely, Vas, Hungary, 9700

Semmelweis Egyetem

Budapest, Hungary, 1083

Petz Aladár Megyei Oktató Kórház

Győr, Hungary, 9023

Israel

Yitzhak Shamir Medical Center

Be'er Ya'aqov, Central District, Israel, 7030000

Bnai Zion Medical Center

Haifa, Haifa District, Israel, 31048

Hadassah University Hospital Ein Kerem

Jerusalem, Jerusalem District, Israel

Rambam Health Care Campus

Haifa, Israel, 3109601

Carmel Medical Center

Haifa, Israel, 3436212

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Meir Medical Center

Kfar Saba, Israel, 4428164

Western Galilee Hospital-Nahariya

Nahariya, Israel

Rabin Medical Center - Beilinson Hospital

Petah tikva, Israel, 4941492

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Italy

Azienda Ospedaliero - Universitaria Careggi

Firenze, Florence, Italy, 50134

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy, 71013

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-Cesena, Italy, 47014

Azienda Socio Sanitaria Territoriale Monza - Ospedale San Gerardo

Monza, Monza E Brianza, Italy, 20900

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, Pesaro E Urbino, Italy, 61121

IRCCS Centro di Riferimento Oncologico di Basilicata

Rionero In Vulture, Potenza, Italy, 85028

Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino

Torino, Turin, Italy, 10126

Azienda Ospedaliera Ordine Mauriziano di Torino

Torino, Turin, Italy, 10128

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo - Alessandria

Alessandria, Italy, 15121

Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi

Bologna, Italy, 40138

Ospedale Policlinico San Martino

Genova, Italy, 16132

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milano, Italy, 20122

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milano, Italy, 20162

Azienda Ospedaliera Universitaria Federico II

Napoli, Italy, 80131

Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara

Novara, Italy, 28100

Umberto I - Policlinico di Roma

Roma, Italy, 00161

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy, 20123

Presidio Ospedaliero Universitario Santa Maria della Misericordia

Udine, Italy, 33100

Ospedale di Circolo e Fondazione Macchi

Varese, Italy, 21100

Ospedale Policlinico Giambattista Rossi Borgo Roma

Verona, Italy, 37134

Korea, Republic of

Kyungpook National University Hospital

Daegu, Daegu Gwang'yeogsi, Korea, Republic of, 41944

Inje University Busan Paik Hospital

Busan, Korea, Republic of, 47392

Inje University Haeundae Paik Hospital

Busan, Korea, Republic of, 48108

Seoul National University Bundang Hospital

Seongnam-si, Korea, Republic of, 13620

Severance Hospital

Seoul, Korea, Republic of, 03722

The Catholic University of Korea Seoul Saint Mary's Hospital

Seoul, Korea, Republic of, 06591

Samsung Medical Center

Seoul, Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of

Ulsan University Hospital

Ulsan, Korea, Republic of, 44033

New Zealand

North Shore Hospital

Auckland, New Zealand, 0622

Middlemore Clinical Trials

Auckland, New Zealand, 2025

Poland

Klinika Hematologii Nowotworów Krwi i Transplantacji Szpiku

Wrocław, Dolnoslaskie, Poland, 50-367

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, Lubelskie, Poland, 20-081

Szpital Uniwersytecki w Krakowie

Kraków, Malopolskie, Poland, 31-501

Instytut Hematologii I Transfuzjologii

Warszawa, Mazowieckie, Poland, 02-776

Alvamed Zakład Specjalistycznej Opieki Zdrowotnej

Warszawa, Mazowieckie, Poland, 03-401

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie

Kraków, Małopolskie, Poland, 31-826

Szpital Wojewódzki w Opolu

Opole, Opolskie, Poland, 45-064

Uniwersyteckie Centrum Kliniczne w Gdańsku

Gdańsk, Pomorskie, Poland, 80-214

Silesian Healthy Blood Clinic

Chorzów, Salskie, Poland, 41-503

Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi

Łódź, Poland, 93-513

Romania

Spitalul Filantropia - Craiova

Craiova, Dolj, Romania, 200143

Institutul Regional De Oncologie Iasi

Iaşi, Iasi County, Romania, 700483

Spitalul Clinic Judetean De Urgenta Târgu Mureș

Târgu-Mureş, Mureș, Romania, 540136

Laboratul clinic MedLife-Policlinica de Diagnostic Rapid Brasov

Braşov, Romania, 500366

Coltea - Spital Clinic

Bucharest, Romania, 030 171

Singapore

Singapore General Hospital

Singapore, Singapore, 169608

Tan Tock Seng Hospital

Singapore, Singapore, 308433

Spain

Hospital Universitario Central de Asturias

Oviedo, Asturias, Spain, 33011

Institut Hospital del Mar d'Investigacions Mèdiques

Barcelona, Spain, 08003

Hospital Universitari Vall d'Hebrón

Barcelona, Spain, 08035

Hospital Germans Trias i Pujol

Barcelona, Spain, 08916

Hospital San Pedro de Alcantara

Cáceres, Spain, 10003

Institut Català d'Oncologia Girona

Girona, Spain, 17007

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario Virgen de la Victoria

Málaga, Spain, 29010

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, Spain, 37007

Hospital Universitario Virgen del Rocío

Sevilla, Spain, 41013

Hospital Universitario La Fe

Valencia, Spain, 46009

Hospital de Día Quirónsalud Zaragoza

Zaragoza, Spain, 50012

Sweden

Karolinska Universitetssjukhuset Solna

Solna, Stockholm, Sweden, 171 76

Sahlgrenska Universitetssjukhuset

Göteborg, Västra Götalands Län, Sweden, 413 45

Uddevalla Sjukhus

Uddevalla, Sweden, 45153

Taiwan

Chiayi Chang Gung Memorial Hospital

Puzi City, Chaiyi, Taiwan, 613

China Medical University Hospital

Taichung City, Taichung, Taiwan, 40447

National Taiwan University Hospital

Taipei, Taiwan, 10002

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan, Taiwan, 333

United Kingdom

United Lincolnshire Hospitals NHS Trust

Boston, England, United Kingdom, PE21 9QS

University Hospitals Bristol NHS Foundation Trust

Bristol, England, United Kingdom, BS2 8ED

University College London Hospitals NHS Foundation Trust

London, England, United Kingdom, NW1 2PG

Guy's and Saint Thomas' NHS Foundation Trust

London, England, United Kingdom, SE1 9RT

Imperial College Healthcare NHS Trust

London, England, United Kingdom, W12 0HS

University Hospital Southampton NHS Foundation Trust

Southampton, England, United Kingdom, SO16 6YD

NHS Lanarkshire

Airdrie, Scotland, United Kingdom, ML6 0JS

Sponsors and Collaborators

Sierra Oncology LLC - a GSK company

Investigators

• Principal Investigator: Srdan Verstovsek, M.D., Ph.D.; Department of Leukemia, The University of Texas MD Anderson Cancer Center
• Principal Investigator: Ruben Mesa; UT Health San Antonio Cancer Center, San Antonio, TX, USA

  Study Documents (Full-Text)

Documents provided by Sierra Oncology LLC - a GSK company:

Study Protocol  [PDF] December 18, 2020

Statistical Analysis Plan  [PDF] December 30, 2021

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gerds A, Verstovsek S, Vannucchi A, Al-Ali HK, Lavie D, Kuykendall A, Grosicki S, Iurlo A, Goh YT, Lazaroiu M, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Donahue R, Kawashima J, Mesa R. MPN-483 Thrombocytopenic Myelofibrosis (MF) Patients Previously Treated With a JAK Inhibitor in a Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) [MOMENTUM]. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S340. doi: 10.1016/S2152-2650(22)01464-1.

• Responsible Party: Sierra Oncology LLC - a GSK company
• ClinicalTrials.gov Identifier: NCT04173494
• Other Study ID Numbers: SRA-MMB-301
• First Posted: November 22, 2019
• Results First Posted: December 22, 2022
• Last Update Posted: November 1, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sierra Oncology LLC - a GSK company:

Myelofibrosis; JAK inhibitor; Danazol; Momelotinib; Functional Iron deficiency; Activin receptor type 1; Anemia; Transfusion; Hepcidin; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases

Additional relevant MeSH terms:

Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Platelet Disorders; Blood Coagulation Disorders; Hemorrhagic Disorders; Danazol; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action