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

October 30, 2023 updated by: Sierra Oncology LLC - a GSK company

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

MOMENTUM Contact Email: GSKClinicalSupportHD@gsk.com

Study Type

Interventional

Enrollment (Actual)

195

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Australian Capital Territory
      • Garran, Australian Capital Territory, Australia, 2605
        • Canberra Region Cancer Centre
    • New South Wales
      • Waratah, New South Wales, Australia, 2298
        • Calvary Mater Newcastle Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Perth Radiological Clinic - Magnetic Resonance Centre
  • Austria
      • Steyr, Austria, 4400
        • Oberösterreichische Gesundheitsholding GmbH
    • Tyrol
      • Innsbruck, Tyrol, Austria, 6020
        • Medizinische Universität Innsbruck
    • Upper Austria
      • Linz, Upper Austria, Austria, 4020
        • Ordensklinikum Linz Elisabethinen
    • Vienna
      • Wien, Vienna, Austria, 1090
        • Medizinische Universitat Wien
  • Belgium
      • Antwerpen, Belgium, 2060
        • Ziekenhuis Netwerk Antwerpen Stuivenberg
      • Liège, Belgium, B-4000
        • Centre Hospitalier Universitaire de Liege
    • Brussels
      • Bruxelles, Brussels, Belgium, 1070
        • Hopital Erasme
    • Hainaut
      • Charleroi, Hainaut, Belgium, 6000
        • Grand Hôpital De Charleroi - Notre Dame
    • West-Vlaanderen
      • Brugge, West-Vlaanderen, Belgium, 8000
        • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
      • Sofia, Bulgaria, 1756
        • National Specialized Hospital for Active Treatment of Haematologic Diseases
      • Sofia, Bulgaria, 1431
        • University Hospital St. Ivan Rilski
      • Sofia, Bulgaria, 1431
        • University Multiprofile Hospital For Active Treatment Aleksandrovska
  • Canada
      • Québec, Canada, G1J 1Z4
        • Hôpital de L'Enfant-Jésus
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • Saint Paul's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • Queen Elizabeth II Health Sciences Centre - Halifax Infirmary
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • McMaster University Medical Center
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
    • Quebec
      • Montréal, Quebec, Canada, H3H 2R9
        • Research Institute of the McGill University Health Centre
  • Czechia
    • Jihormoravsky Kraj
      • Brno, Jihormoravsky Kraj, Czechia, 625 00
        • Fakultni Nemocnice Brno
  • Denmark
    • Hovedstaden
      • Herlev, Hovedstaden, Denmark, 2730
        • Herlev Hospital
    • Nordjylland
      • Aalborg, Nordjylland, Denmark, 9000
        • Aalborg Universitetshospital - Syd
    • Sjælland
      • Roskilde, Sjælland, Denmark, 4000
        • Sjællands Universitetshospital - Roskilde
    • Syddanmark
      • Odense, Syddanmark, Denmark, 5000
        • Odense Universitetshospital
  • France
      • Angers, France, 49 933
        • Centre Hosptitalier Universitaire Angers
      • Lille, France, 59000
        • Hopital Saint-Vincent de Paul - Lille
      • Marseille, France, 13385
        • Hôpital de la Conception
      • Mulhouse, France, 68100
        • Hôpital Emile Muller
      • Nantes, France, 44000
        • Centre Hospitalier Universitaire Nantes - Hotel Dieu
      • Poitiers, France, 86021
        • Centre Hospitalier Universitaire de Poitiers
    • Aquitaine
      • Pessac, Aquitaine, France, 33604
        • Hôpital Haut-Lévêque
    • Basse-Normandie
      • Caen, Basse-Normandie, France, 14033
        • Hospital Center University Of Caen Normandie
    • Hauts-de-France
      • Lille, Hauts-de-France, France, 59037
        • Hopital Claude Huriez
    • Ile-de-France
      • Paris, Ile-de-France, France, 75010
        • Hôpital Saint-Louis
      • Paris, Ile-de-France, France, 75571
        • Hopital Saint-Antoine
    • Limousin
      • Limoges, Limousin, France, 87042
        • Centre Hospitalier Universitaire Limoges
    • Nord Pas-Des-Calais
      • Lens, Nord Pas-Des-Calais, France, 62307
        • Centre Hospitalier de LENS
    • Pays De La Loire
      • Le Mans, Pays De La Loire, France, 72037
        • Centre Hospitalier Le Mans
    • Picardie
      • Amiens, Picardie, France, 80054
        • Centre Hospitalier Universitaire Amiens-Picardie - Site Sud
    • Provence-Alpes-Côte d'Azur
      • Nice, Provence-Alpes-Côte d'Azur, France, 06200
        • Hôpital l'Archet
    • Rhone-Alps
      • Pierre-Bénite, Rhone-Alps, France, 69495
        • Centre hospitalier Lyon-Sud
  • Germany
      • Köln, Germany, 50937
        • Uniklinik Köln
      • Lübeck, Germany, 23538
        • Universitatsklinikum Schleswig-Holstein - Campus Lubeck
      • Mutlangen, Germany, 73557
        • Kliniken Ostalb - Stauferklinikum Schwäbisch Gmünd
    • Nordrhein-Westfalen
      • Aachen, Nordrhein-Westfalen, Germany, 52074
        • Universitätsklinikum Aachen
      • Essen, Nordrhein-Westfalen, Germany, 45147
        • Universitatsklinikum Essen
      • Minden, Nordrhein-Westfalen, Germany, 32429
        • Johannes Wesling Klinikum Minden
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Universitatsklinikum Carl Gustav Carus Dresden
      • Leipzig, Sachsen, Germany, 04103
        • Universitätsklinikum Leipzig
    • Sachsen-Anhalt
      • Halle, Sachsen-Anhalt, Germany, 06120
        • Universitätsklinikum Halle
    • Thuringen
      • Jena, Thuringen, Germany, 07747
        • Universitatsklinikum Jena
  • Hungary
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem
      • Győr, Hungary, 9023
        • Petz Aladar Megyei Oktato Korhaz
    • Baranya
      • Pécs, Baranya, Hungary, 7624
        • Pécsi Tudományegyetem Klinikai Központ
    • Hajdu-Bihar
      • Debrecen, Hajdu-Bihar, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont
    • Komárom-Esztergom
      • Tatabánya, Komárom-Esztergom, Hungary, 2800
        • Szent Borbala Korhaz
    • Pest
      • Budapest, Pest, Hungary, 1097
        • Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet - Szent László Telephely
    • Somogy
      • Kaposvár, Somogy, Hungary, 7400
        • Somogy Megyei Kaposi Mór Oktató Kórház
    • Szabolcs-Szatmár-Bereg
      • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
        • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
    • Vas
      • Szombathely, Vas, Hungary, 9700
        • Markusovszky Egyetemi Oktatókórház Szombathely
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Haifa, Israel, 3436212
        • Carmel Medical Center
      • Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center
      • Kfar Saba, Israel, 4428164
        • Meir Medical Center
      • Nahariya, Israel
        • Western Galilee Hospital-Nahariya
      • Petah tikva, Israel, 4941492
        • Rabin Medical Center - Beilinson Hospital
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center
    • Central District
      • Be'er Ya'aqov, Central District, Israel, 7030000
        • Yitzhak Shamir Medical Center
    • Haifa District
      • Haifa, Haifa District, Israel, 31048
        • Bnai Zion Medical Center
    • Jerusalem District
      • Jerusalem, Jerusalem District, Israel
        • Hadassah University Hospital Ein Kerem
  • Italy
      • Alessandria, Italy, 15121
        • Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo - Alessandria
      • Bologna, Italy, 40138
        • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
      • Genova, Italy, 16132
        • Ospedale Policlinico San Martino
      • Milano, Italy, 20122
        • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
      • Milano, Italy, 20162
        • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
      • Napoli, Italy, 80131
        • Azienda Ospedaliera Universitaria Federico II
      • Novara, Italy, 28100
        • Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
      • Roma, Italy, 00161
        • Umberto I - Policlinico di Roma
      • Roma, Italy, 20123
        • Fondazione Policlinico Universitario Agostino Gemelli
      • Udine, Italy, 33100
        • Presidio Ospedaliero Universitario Santa Maria della Misericordia
      • Varese, Italy, 21100
        • Ospedale di Circolo e Fondazione Macchi
      • Verona, Italy, 37134
        • Ospedale Policlinico Giambattista Rossi Borgo Roma
    • Florence
      • Firenze, Florence, Italy, 50134
        • Azienda Ospedaliero - Universitaria Careggi
    • Foggia
      • San Giovanni Rotondo, Foggia, Italy, 71013
        • Ospedale Casa Sollievo della Sofferenza
    • Forli-Cesena
      • Meldola, Forli-Cesena, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
    • Monza E Brianza
      • Monza, Monza E Brianza, Italy, 20900
        • Azienda Socio Sanitaria Territoriale Monza - Ospedale San Gerardo
    • Pesaro E Urbino
      • Pesaro, Pesaro E Urbino, Italy, 61121
        • Azienda Ospedaliera Ospedali Riuniti Marche Nord
    • Potenza
      • Rionero In Vulture, Potenza, Italy, 85028
        • IRCCS Centro di Riferimento Oncologico di Basilicata
    • Turin
      • Torino, Turin, Italy, 10126
        • Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
      • Torino, Turin, Italy, 10128
        • Azienda Ospedaliera Ordine Mauriziano di Torino
  • Korea, Republic of
      • Busan, Korea, Republic of, 48108
        • Inje University Haeundae Paik Hospital
      • Busan, Korea, Republic of, 47392
        • Inje University Busan Paik Hospital
      • Seongnam-si, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea Seoul Saint Mary's Hospital
      • Ulsan, Korea, Republic of, 44033
        • Ulsan University Hospital
    • Daegu Gwang'yeogsi
      • Daegu, Daegu Gwang'yeogsi, Korea, Republic of, 41944
        • Kyungpook National University Hospital
  • New Zealand
      • Auckland, New Zealand, 0622
        • North Shore Hospital
      • Auckland, New Zealand, 2025
        • Middlemore Clinical Trials
  • Poland
      • Łódź, Poland, 93-513
        • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
    • Dolnoslaskie
      • Wrocław, Dolnoslaskie, Poland, 50-367
        • Klinika Hematologii Nowotworów Krwi i Transplantacji Szpiku
    • Lubelskie
      • Lublin, Lubelskie, Poland, 20-081
        • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
    • Malopolskie
      • Kraków, Malopolskie, Poland, 31-501
        • Szpital Uniwersytecki w Krakowie
    • Mazowieckie
      • Warszawa, Mazowieckie, Poland, 02-776
        • Instytut Hematologii i Transfuzjologii
      • Warszawa, Mazowieckie, Poland, 03-401
        • Alvamed Zakład Specjalistycznej Opieki Zdrowotnej
    • Małopolskie
      • Kraków, Małopolskie, Poland, 31-826
        • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
    • Opolskie
      • Opole, Opolskie, Poland, 45-064
        • Szpital Wojewódzki w Opolu
    • Pomorskie
      • Gdańsk, Pomorskie, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne w Gdańsku
    • Salskie
      • Chorzów, Salskie, Poland, 41-503
        • Silesian Healthy Blood Clinic
  • Romania
      • Braşov, Romania, 500366
        • Laboratul clinic MedLife-Policlinica de Diagnostic Rapid Brasov
      • Bucharest, Romania, 030 171
        • Coltea - Spital Clinic
    • Dolj
      • Craiova, Dolj, Romania, 200143
        • Spitalul Filantropia - Craiova
    • Iasi County
      • Iaşi, Iasi County, Romania, 700483
        • Institutul Regional de Oncologie Iasi
    • Mureș
      • Târgu-Mureş, Mureș, Romania, 540136
        • Spitalul Clinic Judetean de Urgenta Targu Mures
  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital
      • Singapore, Singapore, 308433
        • Tan Tock Seng Hospital
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08916
        • Hospital Germans Trias i Pujol
      • Barcelona, Spain, 08003
        • Institut Hospital del Mar d'Investigacions Mèdiques
      • Cáceres, Spain, 10003
        • Hospital San Pedro de Alcántara
      • Girona, Spain, 17007
        • Institut Català D'Oncologia Girona
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon Y Cajal
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Salamanca, Spain, 37007
        • Complejo Asistencial Universitario de Salamanca - Hospital Clínico
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocío
      • Valencia, Spain, 46009
        • Hospital Universitario La Fe
      • Zaragoza, Spain, 50012
        • Hospital de Día Quirónsalud Zaragoza
    • Asturias
      • Oviedo, Asturias, Spain, 33011
        • Hospital Universitario Central de Asturias
  • Sweden
      • Uddevalla, Sweden, 45153
        • Uddevalla Sjukhus
    • Stockholm
      • Solna, Stockholm, Sweden, 171 76
        • Karolinska Universitetssjukhuset Solna
    • Västra Götalands Län
      • Göteborg, Västra Götalands Län, Sweden, 413 45
        • Sahlgrenska Universitetssjukhuset
  • Taiwan
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taoyuan, Taiwan, 333
        • Chang Gung Memorial Hospital - Linkou Branch
    • Chaiyi
      • Puzi City, Chaiyi, Taiwan, 613
        • Chiayi Chang Gung Memorial Hospital
    • Taichung
      • Taichung City, Taichung, Taiwan, 40447
        • China Medical University Hospital
  • United Kingdom
    • England
      • Boston, England, United Kingdom, PE21 9QS
        • United Lincolnshire Hospitals NHS Trust
      • Bristol, England, United Kingdom, BS2 8ED
        • University Hospitals Bristol NHS Foundation Trust
      • London, England, United Kingdom, NW1 2PG
        • University College London Hospitals Nhs Foundation Trust
      • London, England, United Kingdom, SE1 9Rt
        • Guy's and Saint Thomas' NHS Foundation Trust
      • London, England, United Kingdom, W12 0HS
        • Imperial College Healthcare NHS Trust
      • Southampton, England, United Kingdom, SO16 6YD
        • University Hospital Southampton NHS Foundation Trust
    • Scotland
      • Airdrie, Scotland, United Kingdom, ML6 0JS
        • NHS Lanarkshire
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital - Phoenix
    • California
      • Irvine, California, United States, 92614
        • Irvine Center for Clinical Research
      • Los Angeles, California, United States, 91011
        • Norris Comprehensive Cancer Center
      • Whittier, California, United States, 90603
        • American Institute of Research - Whittier
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital Anschutz Cancer Pavilion
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Georgetown University Medical Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Illinois
      • Rolling Meadows, Illinois, United States, 60008
        • Northwest Oncology & Hematology - Rolling Meadows
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine in Saint Louis
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center - Presbyterian Hospital
    • Ohio
      • Avon, Ohio, United States, 44011
        • Cleveland Clinic - Richard E. Jacobs Health Center
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Allegheny Health Network
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Md Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • The University of Texas Health Science Center at San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Danocrine
Drug: Placebo to match momelotinib
Momelotinib placebo tablets will be self-administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 24
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.
Baseline and Week 24
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.
Baseline and Week 24
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.
Baseline and Week 24
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.
Up to 24 weeks
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.
Up to 24 weeks
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.
Up to a maximum of 151 weeks
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).
Up to a maximum of 151 weeks
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.
Up to Week 24
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.
Week 24
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.
Baseline and Week 24
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.
Week 24
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).
Up to a maximum of 151 weeks
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.
Up to Week 24
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.
From Week 24 to a maximum of 151 weeks
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.
Up to a maximum of 151 weeks
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).
Up to a maximum of 151 weeks
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.
Baseline and Week 24
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.
Baseline and Week 24
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.
Baseline and Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2020

Primary Completion (Actual)

December 3, 2021

Study Completion (Actual)

December 29, 2022

Study Registration Dates

First Submitted

November 20, 2019

First Submitted That Met QC Criteria

November 20, 2019

First Posted (Actual)

November 22, 2019

Study Record Updates

Last Update Posted (Actual)

November 1, 2023

Last Update Submitted That Met QC Criteria

October 30, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SRA-MMB-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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