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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04173494




Registration number
NCT04173494
Ethics application status
Date submitted
20/11/2019
Date registered
22/11/2019

Titles & IDs
Public title
A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)
Scientific 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
Secondary ID [1] 0 0
SRA-MMB-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis 0 0
Post-polycythemia Vera Myelofibrosis 0 0
Post-essential Thrombocythemia Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Momelotinib
Treatment: Drugs - Placebo to match danazol
Treatment: Drugs - Danazol
Treatment: Drugs - Placebo to match momelotinib

Experimental: Momelotinib - Participants will receive momelotinib plus placebo to match danazol

Active comparator: Danazol - Participants will receive danazol plus placebo to match momelotinib


Treatment: Drugs: Momelotinib
Momelotinib tablets will be self-administered orally once daily

Treatment: Drugs: Placebo to match danazol
Danazol placebo capsules will be self-administered orally twice daily

Treatment: Drugs: Danazol
Danazol capsules will be self-administered orally twice daily

Treatment: Drugs: Placebo to match momelotinib
Momelotinib placebo tablets will be self-administered orally once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Total Symptom Score (TSS) Response Rate at Week 24
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [1] 0 0
Percentage of Participants With Transfusion Independence (TI) at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Splenic Response Rate (SRR) of >=25% at Week 24
Timepoint [2] 0 0
Baseline and Week 24
Secondary outcome [3] 0 0
Change From Baseline in MFSAF TSS at Week 24
Timepoint [3] 0 0
Baseline and Week 24
Secondary outcome [4] 0 0
Splenic Response Rate (SRR) of >= 35% at Week 24
Timepoint [4] 0 0
Baseline and Week 24
Secondary outcome [5] 0 0
Percentage of Participants With Zero RBC Units Transfused Over 24-Weeks
Timepoint [5] 0 0
Up to 24 weeks
Secondary outcome [6] 0 0
Percentage of Participants With <=4 RBC Units Transfused Over 24-weeks
Timepoint [6] 0 0
Up to 24 weeks
Secondary outcome [7] 0 0
Duration of MFSAF TSS Response
Timepoint [7] 0 0
Up to a maximum of 151 weeks
Secondary outcome [8] 0 0
Duration of TI Response
Timepoint [8] 0 0
Up to a maximum of 151 weeks
Secondary outcome [9] 0 0
Mean Cumulative Number of Whole Blood Units Transfused Over 24 Weeks
Timepoint [9] 0 0
Up to Week 24
Secondary outcome [10] 0 0
Percentage of Participants With Transfusion Dependence (TD) Status at Week 24
Timepoint [10] 0 0
Week 24
Secondary outcome [11] 0 0
Percentage of Participants With a Hemoglobin Response
Timepoint [11] 0 0
Baseline and Week 24
Secondary outcome [12] 0 0
Number of Baseline TD Participants With TI Status at Week 24
Timepoint [12] 0 0
Week 24
Secondary outcome [13] 0 0
Duration of TI in Baseline TD Participants
Timepoint [13] 0 0
Up to a maximum of 151 weeks
Secondary outcome [14] 0 0
Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- up to Week 24
Timepoint [14] 0 0
Up to Week 24
Secondary outcome [15] 0 0
Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- From Week 24 to a Maximum of 151 Weeks
Timepoint [15] 0 0
From Week 24 to a maximum of 151 weeks
Secondary outcome [16] 0 0
Overall Survival (OS)
Timepoint [16] 0 0
Up to a maximum of 151 weeks
Secondary outcome [17] 0 0
Leukemia-free Survival (LFS)
Timepoint [17] 0 0
Up to a maximum of 151 weeks
Secondary outcome [18] 0 0
Change From Baseline in Disease-related Fatigue as Assessed by MFSAF TSS v4.0 at Week 24
Timepoint [18] 0 0
Baseline and Week 24
Secondary outcome [19] 0 0
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
Timepoint [19] 0 0
Baseline and Week 24
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
Baseline and Week 24

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Canberra Region Cancer Centre - Garran
Recruitment hospital [2] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Perth Radiological Clinic - Magnetic Resonance Centre - Perth
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Austria
State/province [13] 0 0
Tyrol
Country [14] 0 0
Austria
State/province [14] 0 0
Upper Austria
Country [15] 0 0
Austria
State/province [15] 0 0
Vienna
Country [16] 0 0
Austria
State/province [16] 0 0
Steyr
Country [17] 0 0
Belgium
State/province [17] 0 0
Brussels
Country [18] 0 0
Belgium
State/province [18] 0 0
Hainaut
Country [19] 0 0
Belgium
State/province [19] 0 0
West-Vlaanderen
Country [20] 0 0
Belgium
State/province [20] 0 0
Antwerpen
Country [21] 0 0
Belgium
State/province [21] 0 0
Liège
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Pleven
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Sofia
Country [24] 0 0
Canada
State/province [24] 0 0
British Columbia
Country [25] 0 0
Canada
State/province [25] 0 0
Nova Scotia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Canada
State/province [28] 0 0
Québec
Country [29] 0 0
Czechia
State/province [29] 0 0
Jihormoravsky Kraj
Country [30] 0 0
Denmark
State/province [30] 0 0
Hovedstaden
Country [31] 0 0
Denmark
State/province [31] 0 0
Nordjylland
Country [32] 0 0
Denmark
State/province [32] 0 0
Sjælland
Country [33] 0 0
Denmark
State/province [33] 0 0
Syddanmark
Country [34] 0 0
France
State/province [34] 0 0
Aquitaine
Country [35] 0 0
France
State/province [35] 0 0
Basse-Normandie
Country [36] 0 0
France
State/province [36] 0 0
Hauts-de-France
Country [37] 0 0
France
State/province [37] 0 0
Ile-de-France
Country [38] 0 0
France
State/province [38] 0 0
Limousin
Country [39] 0 0
France
State/province [39] 0 0
Nord Pas-Des-Calais
Country [40] 0 0
France
State/province [40] 0 0
Pays De La Loire
Country [41] 0 0
France
State/province [41] 0 0
Picardie
Country [42] 0 0
France
State/province [42] 0 0
Provence-Alpes-Côte d'Azur
Country [43] 0 0
France
State/province [43] 0 0
Rhone-Alps
Country [44] 0 0
France
State/province [44] 0 0
Angers
Country [45] 0 0
France
State/province [45] 0 0
Lille
Country [46] 0 0
France
State/province [46] 0 0
Marseille
Country [47] 0 0
France
State/province [47] 0 0
Mulhouse
Country [48] 0 0
France
State/province [48] 0 0
Nantes
Country [49] 0 0
France
State/province [49] 0 0
Poitiers
Country [50] 0 0
Germany
State/province [50] 0 0
Nordrhein-Westfalen
Country [51] 0 0
Germany
State/province [51] 0 0
Sachsen-Anhalt
Country [52] 0 0
Germany
State/province [52] 0 0
Sachsen
Country [53] 0 0
Germany
State/province [53] 0 0
Thuringen
Country [54] 0 0
Germany
State/province [54] 0 0
Köln
Country [55] 0 0
Germany
State/province [55] 0 0
Lübeck
Country [56] 0 0
Germany
State/province [56] 0 0
Mutlangen
Country [57] 0 0
Hungary
State/province [57] 0 0
Baranya
Country [58] 0 0
Hungary
State/province [58] 0 0
Hajdu-Bihar
Country [59] 0 0
Hungary
State/province [59] 0 0
Komárom-Esztergom
Country [60] 0 0
Hungary
State/province [60] 0 0
Pest
Country [61] 0 0
Hungary
State/province [61] 0 0
Somogy
Country [62] 0 0
Hungary
State/province [62] 0 0
Szabolcs-Szatmár-Bereg
Country [63] 0 0
Hungary
State/province [63] 0 0
Vas
Country [64] 0 0
Hungary
State/province [64] 0 0
Budapest
Country [65] 0 0
Hungary
State/province [65] 0 0
Gyor
Country [66] 0 0
Israel
State/province [66] 0 0
Central District
Country [67] 0 0
Israel
State/province [67] 0 0
Haifa District
Country [68] 0 0
Israel
State/province [68] 0 0
Jerusalem District
Country [69] 0 0
Israel
State/province [69] 0 0
Haifa
Country [70] 0 0
Israel
State/province [70] 0 0
Jerusalem
Country [71] 0 0
Israel
State/province [71] 0 0
Kfar Saba
Country [72] 0 0
Israel
State/province [72] 0 0
Nahariya
Country [73] 0 0
Israel
State/province [73] 0 0
Petah tikva
Country [74] 0 0
Israel
State/province [74] 0 0
Tel Aviv
Country [75] 0 0
Italy
State/province [75] 0 0
Florence
Country [76] 0 0
Italy
State/province [76] 0 0
Foggia
Country [77] 0 0
Italy
State/province [77] 0 0
Forli-Cesena
Country [78] 0 0
Italy
State/province [78] 0 0
Monza E Brianza
Country [79] 0 0
Italy
State/province [79] 0 0
Pesaro E Urbino
Country [80] 0 0
Italy
State/province [80] 0 0
Potenza
Country [81] 0 0
Italy
State/province [81] 0 0
Turin
Country [82] 0 0
Italy
State/province [82] 0 0
Alessandria
Country [83] 0 0
Italy
State/province [83] 0 0
Bologna
Country [84] 0 0
Italy
State/province [84] 0 0
Genova
Country [85] 0 0
Italy
State/province [85] 0 0
Milano
Country [86] 0 0
Italy
State/province [86] 0 0
Napoli
Country [87] 0 0
Italy
State/province [87] 0 0
Novara
Country [88] 0 0
Italy
State/province [88] 0 0
Roma
Country [89] 0 0
Italy
State/province [89] 0 0
Udine
Country [90] 0 0
Italy
State/province [90] 0 0
Varese
Country [91] 0 0
Italy
State/province [91] 0 0
Verona
Country [92] 0 0
Korea, Republic of
State/province [92] 0 0
Daegu Gwang'yeogsi
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Busan
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Seongnam-si
Country [95] 0 0
Korea, Republic of
State/province [95] 0 0
Seoul
Country [96] 0 0
Korea, Republic of
State/province [96] 0 0
Ulsan
Country [97] 0 0
New Zealand
State/province [97] 0 0
Auckland
Country [98] 0 0
Poland
State/province [98] 0 0
Dolnoslaskie
Country [99] 0 0
Poland
State/province [99] 0 0
Lubelskie
Country [100] 0 0
Poland
State/province [100] 0 0
Malopolskie
Country [101] 0 0
Poland
State/province [101] 0 0
Mazowieckie
Country [102] 0 0
Poland
State/province [102] 0 0
Opolskie
Country [103] 0 0
Poland
State/province [103] 0 0
Pomorskie
Country [104] 0 0
Poland
State/province [104] 0 0
Salskie
Country [105] 0 0
Poland
State/province [105] 0 0
Lódz
Country [106] 0 0
Romania
State/province [106] 0 0
Dolj
Country [107] 0 0
Romania
State/province [107] 0 0
Iasi County
Country [108] 0 0
Romania
State/province [108] 0 0
Mure?
Country [109] 0 0
Romania
State/province [109] 0 0
Brasov
Country [110] 0 0
Romania
State/province [110] 0 0
Bucharest
Country [111] 0 0
Singapore
State/province [111] 0 0
Singapore
Country [112] 0 0
Spain
State/province [112] 0 0
Asturias
Country [113] 0 0
Spain
State/province [113] 0 0
Barcelona
Country [114] 0 0
Spain
State/province [114] 0 0
Cáceres
Country [115] 0 0
Spain
State/province [115] 0 0
Girona
Country [116] 0 0
Spain
State/province [116] 0 0
Madrid
Country [117] 0 0
Spain
State/province [117] 0 0
Málaga
Country [118] 0 0
Spain
State/province [118] 0 0
Salamanca
Country [119] 0 0
Spain
State/province [119] 0 0
Sevilla
Country [120] 0 0
Spain
State/province [120] 0 0
Valencia
Country [121] 0 0
Spain
State/province [121] 0 0
Zaragoza
Country [122] 0 0
Sweden
State/province [122] 0 0
Stockholm
Country [123] 0 0
Sweden
State/province [123] 0 0
Västra Götalands Län
Country [124] 0 0
Sweden
State/province [124] 0 0
Uddevalla
Country [125] 0 0
Taiwan
State/province [125] 0 0
Chaiyi
Country [126] 0 0
Taiwan
State/province [126] 0 0
Taichung
Country [127] 0 0
Taiwan
State/province [127] 0 0
Taipei
Country [128] 0 0
Taiwan
State/province [128] 0 0
Taoyuan
Country [129] 0 0
United Kingdom
State/province [129] 0 0
England
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sierra Oncology LLC - a GSK company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Srdan Verstovsek, M.D., Ph.D.
Address 0 0
Department of Leukemia, The University of Texas MD Anderson Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.