Description:
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.
Title
- Brief Title: A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Patients (MOMENTUM)
- Official Title: A Randomized, Double-Blind, Phase 3 Study of Momelotinib vs Danazol in Symptomatic, Anemic Subjects With Previously JAKi Treated Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post Essential Thrombocythemia Myelofibrosis
Clinical Trial IDs
- ORG STUDY ID:
SRA-MMB-301
- NCT ID:
NCT04173494
Conditions
- Primary Myelofibrosis
- Post-polycythemia Vera Myelofibrosis
- Post-essential Thrombocythemia Myelofibrosis
Interventions
Drug | Synonyms | Arms |
---|
Momelotinib | MMB, GS-0387, CYT387 | Momelotinib |
Danazol | Danocrine | Danazol |
Placebo to match momelotinib | | Danazol |
Placebo to match danazol | | Momelotinib |
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 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.
Detailed Description
MOMENTUM Contact Email: momentum_clintrials.gov@sierraoncology.com
Trial Arms
Name | Type | Description | Interventions |
---|
Momelotinib | Experimental | Participants will receive momelotinib plus placebo to match danazol | - Momelotinib
- Placebo to match danazol
|
Danazol | Active Comparator | Participants will receive danazol plus placebo to match momelotinib | - Danazol
- Placebo to match momelotinib
|
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Total Symptom Score (TSS) response rate at Week 24 measured using the Myelofibrosis Symptom Assessment Form v4.0 |
Time Frame: | Week 24 landmark. |
Safety Issue: | |
Description: | 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
Measure: | Transfusion independence (TI) status at Week 24 |
Time Frame: | Week 24 landmark. |
Safety Issue: | |
Description: | 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. |
Measure: | Splenic response rate (SRR) at Week 24 |
Time Frame: | Week 24 |
Safety Issue: | |
Description: | Proportion of subjects who have splenic response (reduction in spleen volume of ≥ 35% from baseline) at the end of Week 24 |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Sierra Oncology, Inc. |
Trial Keywords
- Myelofibrosis
- JAK inhibitor
- Danazol
- Momelotinib
- Functional Iron deficiency
- ACVR1
- Anemia
- Transfusion
- Hepcidin
- Myeloproliferative Disorders
- Bone Marrow Diseases
- Hematologic Diseases
Last Updated
June 25, 2021