Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
During the 24 week randomized treatment phase of the study, participants, investigators and sponsor and relevant vendor personnel (with the exception of specified unblinded personnel, for example clinical supply) will remain blinded to the participant's treatment assignment and to aggregate data that may lead to inadvertent unblinding. Participants who continue treatment with momelotinib or danazol after Week 24 in the extended treatment phase will receive unblinded treatment.

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

Status
Completed
Sponsor
Sierra Oncology LLC - a GSK company

Study Contact

Detailed Description

MOMENTUM Contact Email: GSKClinicalSupportHD@gsk.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.