Clinical Trials List
Protocol NumberSRA-MMB-301
NCT Number(ClinicalTrials.gov Identfier)NCT04173494
2019-11-30 - 2022-05-19
Phase III
Not yet recruiting3
Recruiting1
ICD-10Q78.1
Polyostotic fibrous dysplasia
ICD-9756.54
Polyostotic fibrous dysplasia of bone
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
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
Sierra Oncology, Inc
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Chung Kao 無
- 曾振輝 無
- 高小雯 無
- Po-Nan Wang 無
- Lee-Yung Shin 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Ching Yun Hsieh 未分科
- Ming-Hung Tsai 未分科
- Chen-Yuan Lin 未分科
- Tzu-Ting Chen 未分科
- Yu-Min Liao 未分科
- Che-Hung Lin 未分科
- Ching-Chan Lin 未分科
- Ming-Yu Lien 未分科
- Chi-Ching Chen 未分科
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- - - 無
- Chien-Chin Lin 無
- - - 無
- 劉家豪 無
- CHENG-HONG TSAI 無
- MING YAO 無
- 田豐銘 無
- 劉高郎 無
- Jih-Luh Tang 未分科
- Huai-Hsuan Huang 無
- BANG-BIN CHEN 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Primary Myelofibrosis (PMF), Post-Polycythemia Vera (PV) Myelofibrosis, or Post Essential Thrombocythemia (ET) Myelofibrosis
Objectives
Primary
* To determine the efficacy of MMB versus DAN assessed by improvement in Myelofibrosis Symptom Assessment Form v4.0 (MFSAF) total symptom score (TSS) in subjects with PMF, post-PV myelofibrosis (MF), or post-ET MF who were previously treated with approved JAK inhibitor therapy
Test Drug
Momelotinib Tablets；Danazol Capsules
Active Ingredient
Danazol
Momelotinib
Momelotinib
Dosage Form
Film-coated tablets
capsules
capsules
Dosage
50mg, 100mg, 150 mg and 200mg
100mg and 200mg
100mg and 200mg
Endpoints
Primary Outcome Measures :
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 :
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.
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
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 :
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.
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
Inclution 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 at a Screening visit.
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:
o Absolute neutrophil count (ANC) ≥ 0.75 × 10⁹/L.
o Platelet count (PLT) ≥ 25 × 10⁹/L.
o Peripheral blast count < 10%.
o 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).
o Calculated creatinine clearance (CCr) ≥ 30 mL/min according to Cockcroft-Gault.
o Direct bilirubin ≤ 2.0 × ULN.
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 at a Screening visit.
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:
o Absolute neutrophil count (ANC) ≥ 0.75 × 10⁹/L.
o Platelet count (PLT) ≥ 25 × 10⁹/L.
o Peripheral blast count < 10%.
o 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).
o Calculated creatinine clearance (CCr) ≥ 30 mL/min according to Cockcroft-Gault.
o Direct bilirubin ≤ 2.0 × ULN.
Exclusion Criteria
Exclusion Criteria
1. Use of the following treatments within the time periods noted:
a. Prior momelotinib treatment at any time.
b. JAK inhibitor therapy within 2 weeks prior to Randomization.
c. Active anti-MF therapy within 2 weeks prior to Randomization.
d. Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization.
e. Investigational agent within 4 weeks prior to Randomization.
f. Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization.
g. Danazol within 3 months prior to Randomization.
h. Splenic irradiation within 3 months prior to Randomization.
i. 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):
a. 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).
b. Significant active or chronic bleeding event ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization.
c. Unstable angina pectoris within 6 months prior to Randomization.
d. Symptomatic congestive heart failure within 6 months prior to Randomization.
e. Uncontrolled cardiac arrhythmia within 6 months prior to Randomization.
f. QTcF interval > 500 msec, unless attributed to bundle branch block.
g. Current progressive thrombosis despite treatment.
h. History of porphyria.
i. Child-Pugh score ≥ 10.
j. 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.
k. 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.
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.
13. Additional inclusion/exclusion criteria may apply.
1. Use of the following treatments within the time periods noted:
a. Prior momelotinib treatment at any time.
b. JAK inhibitor therapy within 2 weeks prior to Randomization.
c. Active anti-MF therapy within 2 weeks prior to Randomization.
d. Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization.
e. Investigational agent within 4 weeks prior to Randomization.
f. Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization.
g. Danazol within 3 months prior to Randomization.
h. Splenic irradiation within 3 months prior to Randomization.
i. 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):
a. 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).
b. Significant active or chronic bleeding event ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization.
c. Unstable angina pectoris within 6 months prior to Randomization.
d. Symptomatic congestive heart failure within 6 months prior to Randomization.
e. Uncontrolled cardiac arrhythmia within 6 months prior to Randomization.
f. QTcF interval > 500 msec, unless attributed to bundle branch block.
g. Current progressive thrombosis despite treatment.
h. History of porphyria.
i. Child-Pugh score ≥ 10.
j. 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.
k. 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.
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.
13. Additional inclusion/exclusion criteria may apply.
The Estimated Number of Participants
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Taiwan
10 participants
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Global
270 participants
