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Trial record 6 of 14 for:    momelotinib

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04173494
Recruitment Status : Active, not recruiting
First Posted : November 22, 2019
Last Update Posted : February 11, 2022
Information provided by (Responsible Party):
Sierra Oncology, Inc.

Brief Summary:

MOMENTUM is a randomized, double-blind, active control Phase 3 trial intended to confirm the differentiated clinical benefits of the investigational drug momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic subjects 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, UK, and US.

Subjects must be symptomatic with a MFSAF v4.0 Total Symptom Score of ≥ 10 at screening, and be anemic with Hgb < 10 g/dL. For subjects 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.

Subjects will be randomized 2:1 to orally self-administer blinded treatment: MMB plus placebo or DAN plus placebo. Subjects 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 subject tolerates and continues to benefit from MMB.

Subjects 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.

Subjects randomized to receive DAN who are receiving clinical benefit at the end of Week 24 may choose to continue DAN therapy up to Week 48. The comparator treatment, DAN, is an approved medication in the US and in some other countries and is recommended by national guidelines as a treatment for anemia in MF.

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

Detailed Description:
MOMENTUM Contact Email:

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 195 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: During the 24 week randomized treatment phase of the study, subjects, investigators and sponsor and relevant vendor personnel (with the exception of specified unblinded personnel, for example clinical supply) will remain blinded to the subject's treatment assignment and to aggregate data that may lead to inadvertent unblinding. Subjects who continue treatment with momelotinib or danazol after Week 24 in the extended treatment phase will receive unblinded treatment.
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Phase 3 Study to Evaluate the Activity of Momelotinib (MMB) Versus Danazol (DAN) in Symptomatic, Anemic Subjects With Primary Myelofibrosis (PMF), Post-polycythemia Vera (PV) Myelofibrosis, or Post-essential Thrombocythemia (ET) Myelofibrosis Who Were Previously Treated With JAK Inhibitor Therapy
Actual Study Start Date : February 7, 2020
Actual Primary Completion Date : December 3, 2021
Estimated Study Completion Date : April 2028

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

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

Active Comparator: Danazol
Participants will receive danazol plus placebo to match momelotinib
Drug: Danazol
Danazol capsules will be self-administered orally twice daily
Other Name: Danocrine

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

Primary Outcome Measures :
  1. Total Symptom Score (TSS) response rate at Week 24 measured using the Myelofibrosis Symptom Assessment Form v4.0 [ Time Frame: Week 24 landmark. ]
    Difference in TSS response rate at Week 24. TSS response is defined as the proportion of subjects who achieve a ≥ 50% reduction in TSS over the 28 days immediately prior to the end of Week 24 compared to baseline

Secondary Outcome Measures :
  1. Transfusion independence (TI) status at Week 24 [ Time Frame: Week 24 landmark. ]
    Proportion of subjects with TI status at the end of Week 24. TI is defined as not requiring RBC transfusion (except in the case of clinically overt bleeding) for ≥ 12 weeks immediately prior to the end of Week 24, with Hgb levels ≥ 8 g/dL.

  2. Splenic response rate (SRR) at Week 24 [ Time Frame: Week 24 ]
    Proportion of subjects who have splenic response (reduction in spleen volume of ≥ 35% from baseline) at the end of Week 24

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post-PV/ET MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT criteria).
  3. Symptomatic, defined as a TSS of ≥ 10 units assessed by a single MFSAF v4.0 assessment during Screening prior to Day BL1.
  4. Anemic, defined as a Hgb < 10 g/dL in Screening/Baseline period.
  5. 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.
  6. Baseline splenomegaly, defined as having a palpable spleen at ≥ 5 cm, below the left costal margin, or with volume ≥ 450 cm³ on imaging (ultrasound, MRI or CT are acceptable), assessed during Screening at any point prior to Randomization.
  7. High risk, intermediate-2, or intermediate-1 risk MF as defined by DIPSS, or DIPSS-plus.
  8. No allogeneic stem cell transplant planned.
  9. Acceptable laboratory assessments:

    • Absolute neutrophil count (ANC) ≥ 0.75 × 10⁹/L.
    • Platelet count (PLT) ≥ 25 × 10⁹/L (without requirement for platelet transfusion).
    • Peripheral blast count < 10%.
    • Alanine aminotransferase/ glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT) ≤ 3 × 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).
    • Calculated creatinine clearance (CCr) ≥ 30 mL/min according to Cockcroft-Gault.
    • Direct bilirubin ≤ 2.0 × ULN.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. Prostate specific antigen (PSA) > 4 ng/mL.
  4. Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI or CT scan for spleen volume measurement per protocol requirements.
  5. Any of the following (criteria a - k):

    1. Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (subjects 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. QTcF interval > 500 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.
  6. Subjects 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.
  7. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding or thalassemia.
  8. Known positive status for HIV.
  9. Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier (testing required for hepatitis B and C).
  10. Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per CTCAE v5.0.
  11. Presence of peripheral neuropathy ≥ Grade 2 per CTCAE v5.0.
  12. Women who are already pregnant or lactating.

Additional inclusion/exclusion criteria may apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04173494

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Sponsors and Collaborators
Sierra Oncology, Inc.
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Principal Investigator: Srdan Verstovsek, M.D., Ph.D. Department of Leukemia, The University of Texas MD Anderson Cancer Center
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Responsible Party: Sierra Oncology, Inc. Identifier: NCT04173494    
Other Study ID Numbers: SRA-MMB-301
First Posted: November 22, 2019    Key Record Dates
Last Update Posted: February 11, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sierra Oncology, Inc.:
JAK inhibitor
Functional Iron deficiency
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action