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

Primary Myelofibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04173494
• Other study ID #: SRA-MMB-301
• Status: Completed
• Phase: Phase 3
• Start date: February 7, 2020
• Est. completion date: December 29, 2022

Study information

• Verified date: October 2023
• Source: Sierra Oncology LLC - a GSK company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

MOMENTUM Contact Email: GSKClinicalSupportHD@gsk.com

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: December 29, 2022
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Momelotinib
Momelotinib tablets will be self-administered orally once daily
• Placebo to match danazol
Danazol placebo capsules will be self-administered orally twice daily
• Danazol
Danazol capsules will be self-administered orally twice daily
• Placebo to match momelotinib
Momelotinib placebo tablets will be self-administered orally once daily

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Canberra Region Cancer Centre	Garran	Australian Capital Territory
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Perth Radiological Clinic - Magnetic Resonance Centre	Perth	Western Australia
Australia	Calvary Mater Newcastle Hospital	Waratah	New South Wales
Austria	Medizinische Universität Innsbruck	Innsbruck	Tyrol
Austria	Ordensklinikum Linz Elisabethinen	Linz	Upper Austria
Austria	Oberösterreichische Gesundheitsholding GmbH	Steyr
Austria	Medizinische Universität Wien	Wien	Vienna
Belgium	Ziekenhuis Netwerk Antwerpen Stuivenberg	Antwerpen
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge	West-Vlaanderen
Belgium	Hôpital Erasme	Bruxelles	Brussels
Belgium	Grand Hôpital de Charleroi - Notre Dame	Charleroi	Hainaut
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Bulgaria	University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD	Pleven
Bulgaria	National Specialized Hospital for Active Treatment of Haematologic Diseases	Sofia
Bulgaria	University Hospital St. Ivan Rilski	Sofia
Bulgaria	University Multiprofile Hospital For Active Treatment Aleksandrovska	Sofia
Canada	Queen Elizabeth II Health Sciences Centre - Halifax Infirmary	Halifax	Nova Scotia
Canada	McMaster University Medical Center	Hamilton	Ontario
Canada	Research Institute of the McGill University Health Centre	Montréal	Quebec
Canada	Hôpital de l'Enfant-Jésus	Québec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Saint Paul's Hospital	Vancouver	British Columbia
Czechia	Fakultni Nemocnice Brno	Brno	Jihormoravsky Kraj
Denmark	Aalborg Universitetshospital - Syd	Aalborg	Nordjylland
Denmark	Herlev Hospital	Herlev	Hovedstaden
Denmark	Odense Universitetshospital	Odense	Syddanmark
Denmark	Sjællands Universitetshospital - Roskilde	Roskilde	Sjælland
France	Centre Hospitalier Universitaire Amiens-Picardie - Site Sud	Amiens	Picardie
France	Centre Hosptitalier Universitaire Angers	Angers
France	Hospital Center University Of Caen Normandie	Caen	Basse-Normandie
France	Centre Hospitalier Le Mans	Le Mans	Pays De La Loire
France	Centre Hospitalier De Lens	Lens	Nord Pas-Des-Calais
France	Hôpital Claude Huriez	Lille	Hauts-de-France
France	Hôpital Saint-Vincent De Paul - Lille	Lille
France	Centre Hospitalier Universitaire Limoges	Limoges	Limousin
France	Hôpital De La Conception	Marseille
France	Hôpital Emile Muller	Mulhouse
France	Centre Hospitalier Universitaire Nantes - Hôtel Dieu	Nantes
France	Hôpital l'Archet	Nice	Provence-Alpes-Côte d'Azur
France	Hôpital Saint-Antoine	Paris	Ile-de-France
France	Hôpital Saint-Louis	Paris	Ile-de-France
France	Hôpital Haut-Lévêque	Pessac	Aquitaine
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite	Rhone-Alps
France	Centre Hospitalier Universitaire de Poitiers	Poitiers
Germany	Universitätsklinikum Aachen	Aachen	Nordrhein-Westfalen
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden	Sachsen
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Universitätsklinikum Halle	Halle	Sachsen-Anhalt
Germany	Universitätsklinikum Jena	Jena	Thuringen
Germany	Uniklinik Köln	Köln
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitätsklinikum Schleswig-Holstein - Campus Lübeck	Lübeck
Germany	Johannes Wesling Klinikum Minden	Minden	Nordrhein-Westfalen
Germany	Kliniken Ostalb - Stauferklinikum Schwäbisch Gmünd	Mutlangen
Hungary	Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet - Szent László Telephely	Budapest	Pest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen	Hajdu-Bihar
Hungary	Petz Aladár Megyei Oktató Kórház	Gyor
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár	Somogy
Hungary	Szabolcs-Szatmár-Bereg Megyei Kórházak És Egyetemi Oktatókórház	Nyíregyháza	Szabolcs-Szatmár-Bereg
Hungary	Pécsi Tudományegyetem Klinikai Központ	Pécs	Baranya
Hungary	Markusovszky Egyetemi Oktatókórház Szombathely	Szombathely	Vas
Hungary	Szent Borbála Kórház	Tatabánya	Komárom-Esztergom
Israel	Yitzhak Shamir Medical Center	Be'er Ya'aqov	Central District
Israel	Bnai Zion Medical Center	Haifa	Haifa District
Israel	Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Hospital Ein Kerem	Jerusalem	Jerusalem District
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Western Galilee Hospital-Nahariya	Nahariya
Israel	Rabin Medical Center - Beilinson Hospital	Petah tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo - Alessandria	Alessandria
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliero - Universitaria Careggi	Firenze	Florence
Italy	Ospedale Policlinico San Martino	Genova
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola	Forli-Cesena
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Socio Sanitaria Territoriale Monza - Ospedale San Gerardo	Monza	Monza E Brianza
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara	Novara
Italy	Azienda Ospedaliera Ospedali Riuniti Marche Nord	Pesaro	Pesaro E Urbino
Italy	IRCCS Centro di Riferimento Oncologico di Basilicata	Rionero In Vulture	Potenza
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Umberto I - Policlinico di Roma	Roma
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Italy	Azienda Ospedaliera Ordine Mauriziano di Torino	Torino	Turin
Italy	Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino	Torino	Turin
Italy	Presidio Ospedaliero Universitario Santa Maria della Misericordia	Udine
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Italy	Ospedale Policlinico Giambattista Rossi Borgo Roma	Verona
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu	Daegu Gwang'yeogsi
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul Saint Mary's Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
New Zealand	Middlemore Clinical Trials	Auckland
New Zealand	North Shore Hospital	Auckland
Poland	Silesian Healthy Blood Clinic	Chorzów	Salskie
Poland	Uniwersyteckie Centrum Kliniczne w Gdansku	Gdansk	Pomorskie
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie	Kraków	Malopolskie
Poland	Szpital Uniwersytecki w Krakowie	Kraków	Malopolskie
Poland	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lódz
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin	Lubelskie
Poland	Szpital Wojewódzki w Opolu	Opole	Opolskie
Poland	Alvamed Zaklad Specjalistycznej Opieki Zdrowotnej	Warszawa	Mazowieckie
Poland	Instytut Hematologii I Transfuzjologii	Warszawa	Mazowieckie
Poland	Klinika Hematologii Nowotworów Krwi i Transplantacji Szpiku	Wroclaw	Dolnoslaskie
Romania	Laboratul clinic MedLife-Policlinica de Diagnostic Rapid Brasov	Brasov
Romania	Coltea - Spital Clinic	Bucharest
Romania	Spitalul Filantropia - Craiova	Craiova	Dolj
Romania	Institutul Regional De Oncologie Iasi	Iasi	Iasi County
Romania	Spitalul Clinic Judetean De Urgenta Târgu Mure?	Târgu-Mures	Mure?
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Institut Hospital del Mar d'Investigacions Mèdiques	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Institut Català d'Oncologia Girona	Girona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Complejo Asistencial Universitario de Salamanca - Hospital Clínico	Salamanca
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital de Día Quirónsalud Zaragoza	Zaragoza
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg	Västra Götalands Län
Sweden	Karolinska Universitetssjukhuset Solna	Solna	Stockholm
Sweden	Uddevalla Sjukhus	Uddevalla
Taiwan	Chiayi Chang Gung Memorial Hospital	Puzi City	Chaiyi
Taiwan	China Medical University Hospital	Taichung City	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou Branch	Taoyuan
United Kingdom	NHS Lanarkshire	Airdrie	Scotland
United Kingdom	United Lincolnshire Hospitals NHS Trust	Boston	England
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol	England
United Kingdom	Guy's and Saint Thomas' NHS Foundation Trust	London	England
United Kingdom	Imperial College Healthcare NHS Trust	London	England
United Kingdom	University College London Hospitals NHS Foundation Trust	London	England
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton	England
United States	University of Colorado Hospital Anschutz Cancer Pavilion	Aurora	Colorado
United States	Cleveland Clinic - Richard E. Jacobs Health Center	Avon	Ohio
United States	Gabrail Cancer Center	Canton	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Irvine Center for Clinical Research	Irvine	California
United States	Norris Comprehensive Cancer Center	Los Angeles	California
United States	Columbia University Irving Medical Center - Presbyterian Hospital	New York	New York
United States	Mayo Clinic Hospital - Phoenix	Phoenix	Arizona
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Northwest Oncology & Hematology - Rolling Meadows	Rolling Meadows	Illinois
United States	Washington University School of Medicine in Saint Louis	Saint Louis	Missouri
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	American Institute of Research - Whittier	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Sierra Oncology LLC - a GSK company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Romania,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Symptom Score (TSS) Response Rate at 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	Percentage of Participants With Transfusion Independence (TI) at 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
Secondary	Splenic Response Rate (SRR) of >=25% at 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
Secondary	Change From Baseline in MFSAF TSS at 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
Secondary	Splenic Response Rate (SRR) of >= 35% at 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
Secondary	Percentage of Participants With Zero RBC Units Transfused Over 24-Weeks	Percentage of participants with zero RBC units transfused over 24-weeks were reported.	Up to 24 weeks
Secondary	Percentage of Participants With <=4 RBC Units Transfused Over 24-weeks	Percentage of participants with <=4 RBC units transfused over 24-weeks were reported.	Up to 24 weeks
Secondary	Duration of MFSAF TSS Response	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
Secondary	Duration of TI Response	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
Secondary	Mean Cumulative Number of Whole Blood Units Transfused Over 24 Weeks	Cumulative transfusion risk was calculated as the estimated mean cumulative number of whole blood units transfused during the study.	Up to Week 24
Secondary	Percentage of Participants With Transfusion Dependence (TD) Status at 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
Secondary	Percentage of Participants With a Hemoglobin Response	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
Secondary	Number of Baseline TD Participants With TI Status at 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
Secondary	Duration of TI in Baseline TD Participants	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
Secondary	Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- 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
Secondary	Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- 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
Secondary	Overall Survival (OS)	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
Secondary	Leukemia-free Survival (LFS)	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
Secondary	Change From Baseline in Disease-related Fatigue as Assessed by MFSAF TSS v4.0 at 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
Secondary	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	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
Secondary	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	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