Postessential Thrombocythemia (Post-ET) Myelofibrosis, Post-polycythemia Vera (Post-PV) Myelofibrosis, Primary Myelofibrosis (PMF)
Conditions
Brief summary
This study will evaluate the transfusion independence response rate in transfusion-dependent adults with myelofibrosis after treatment with momelotinib (MMB).
Interventions
DRUGMMB
Momelotinib (MMB) tablet administered orally once daily
Sponsors
Sierra Oncology LLC - a GSK company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of PMF or Post PV/ET-MF * Requires myelofibrosis therapy, in the opinion of the investigator * High risk OR intermediate-2 risk defined by dynamic international prognostic scoring system (DIPSS) OR intermediate-1 risk defined by DIPSS and associated with symptomatic splenomegaly and/or hepatomegaly * Transfusion dependent at baseline, defined as ≥ 4 U red blood cell (RBC) transfusion in the 8 weeks prior to first dose of MMB * Acceptable organ function as evidenced by the following: * Platelet Count ≥ 50 x 10\^9/L * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN) or AST or ALT ≤ 5 x ULN if liver is involved by disease process as judged by the investigator * Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance of ≥ 60 mL/min * Direct bilirubin ≤ 2.0 x ULN * Life expectancy of \> 24 weeks * Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception * Lactating females must agree to discontinue nursing before MMB administration * Able to understand and willing to sign the informed consent form Key
Exclusion criteria
* Prior splenectomy * Splenic irradiation within 3 months prior to the first dose of MMB * Prior treatment with MMB * Known positive status of human immunodeficiency virus (HIV) * Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier * Use of strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks prior to the first dose of MMB * Uncontrolled intercurrent illness per protocol * Treatment with a Janus kinase (JAK) inhibitor within 21 days of the planned first dose of MMB * Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 * Unwilling or unable to undergo a MRI per requirements in the study protocol * Unwilling to consent to genomics sampling Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transfusion Independence Response by Week 24 | From baseline to Week 24 | The percentage of subjects who became transfusion independent for ≥ 12 weeks at any time on study. A subject was considered transfusion independent on study if no RBC transfusion occurred in any 12-week period during the 24-week treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Splenic Response Rate at Week 24 | Measured at Week 24 | The percentage of subjects who achieved a ≥ 35% reduction in spleen volume from baseline as measured by MRI at Week 24. |
| Response Rate in Total Symptom Score (TSS) at Week 24 | Measured at Week 24 | The percentage of subjects achieving a ≥ 50% reduction from baseline in TSS at Week 24, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) diary. Total symptom score was assessed using the modified MPN-SAF TSS Version 2, an 8-item questionnaire developed to assess symptom burden and quality of life in patients with MPN. The modified MPN-SAF TSS contained 8 questions, 7 of which were summed to generate the score (the included questions related to tiredness, early satiety, abdominal discomfort, night sweats, itching, bone pain, and pain under the ribs on the left side). Each question is scored on a scale of 0-10, where higher numbers indicate more severe symptoms. For this study, the TSS scale ranges from 0 to 70. The questionnaire was completed daily on an electronic diary device. |
| Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24 | Hepcidin daily change (in nM) was calculated as the predose value subtracted from the 6 hours postdose value at each study visit. Daily hepcidin change at the baseline visit was the difference between 2 values obtained 6 hours apart. No momelotinib was administered on that day. |
| Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24 | Median hepcidin at trough was assessed predose at each study visit. |
| Change in Markers of Iron Metabolism and Anemia - Serum Iron | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in serum iron, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Hemoglobin | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in hemoglobin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in total iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Reticulocytes | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in reticulocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in reticulocytes/erythrocytes%, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Erythropoietin | At Weeks 8 and 20 | Percent change in erythropoietin at Weeks 8 and 20. The baseline erythropoietin value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Erythrocytes | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in erythrocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Transfusion Response Rate by Week 24 | From baseline to Week 24 | The percentage of subjects who became transfusion independent for ≥ 8 weeks, defined as no RBC transfusions for at least an 8-week period at any time on study. |
| Change in Markers of Iron Metabolism and Anemia - Ferritin | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in ferritin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in soluble transferrin receptor, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in transferrin saturation, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in unsaturated iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Platelets | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in platelets, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Leukocytes | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in leukocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Blasts | At Weeks 2 and 4 | Change from baseline in % blasts at Weeks 2 and 4. The baseline % blasts value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Liver Iron Content | Measured at Week 24 | Percent change from baseline in liver iron content assessed by MRI. The baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Pharmacodynamics Biomarker - pSTAT3 | On Day 1 and at Weeks 4 and 24 | Percent change in %pSTAT stimulated CD3+/4+ T cell at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose). |
| Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | On Day 1 and at Weeks 4 and 24 | Percent change in %pSTAT/%tSTAT Stimulated CD3+/4+ T cell ratio at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose). |
| Change in Inflammatory Markers - C-Reactive Protein (CRP) | At Weeks 2, 12 and 24 | Percent change in C-reactive protein at Weeks 2, 12 and 24. The baseline C-reactive protein value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
| Change in Markers of Iron Metabolism and Anemia - Hematocrit | At Weeks 2, 4, 8, 12, 16, 20 and 24 | Percent change from baseline in hematocrit, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit). |
Countries
Canada, United States
Participant flow
Recruitment details
This study enrolled transfusion-dependent myelofibrosis patients at oncology centers in the United States and Canada. Following completion of the 24-week study period, patients who were benefiting had the option to continue maintenance momelotinib treatment in an open-label extension study (NCT02124746).
Participants by arm
| Arm | Count |
|---|---|
| Transfusion Independence Responders Subjects who became transfusion independent by Week 24 | 14 |
| Transfusion Independence Non-Responders Subjects who did not become transfusion independent by Week 24 | 27 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 2 |
| Overall Study | Disease Progression | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Transfusion Independence Responders | Total | Transfusion Independence Non-Responders |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 10 | 70 years STANDARD_DEVIATION 9 | 72 years STANDARD_DEVIATION 7.5 |
| Blasts | 0 % | 2.0 % | 2.0 % |
| C-Reactive Protein | 0.7 mg/dL | 1.2 mg/dL | 1.8 mg/dL |
| Erythrocytes | 3.0 cells*10^6/uL | 2.9 cells*10^6/uL | 2.8 cells*10^6/uL |
| Erythropoietin | 238.7 mIU/mL | 109.8 mIU/mL | 88.1 mIU/mL |
| Ferritin | 605.9 ng/mL | 1008.9 ng/mL | 1259.4 ng/mL |
| Hematocrit | 27.5 % | 25.0 % | 24.0 % |
| Hemoglobin | 8.5 g/dL | 8.0 g/dL | 7.8 g/dL |
| Hepcidin | 22.0 nM | 36.6 nM | 42.4 nM |
| Leukocytes | 6.4 cells*10^3/uL | 6.4 cells*10^3/uL | 8.5 cells*10^3/uL |
| Liver Iron Content | 2.4 mg/g | 3.5 mg/g | 4.2 mg/g |
| Platelets | 190.5 cells*10^3/uL | 146.0 cells*10^3/uL | 134.0 cells*10^3/uL |
| %pSTAT Stimulated CD3+/4+ T cell | 85.1 % | 79.8 % | 77.8 % |
| %pSTAT %tSTAT Stimulated CD3+/4+ T cell Ratio | 0.9 ratio | 0.9 ratio | 0.8 ratio |
| Race/Ethnicity, Customized Black | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Permitted | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 36 Participants | 25 Participants |
| RBC Units Transfused within 8 weeks prior to Enrollment | 5 Units of red blood cell STANDARD_DEVIATION 1.9 | 6 Units of red blood cell STANDARD_DEVIATION 2.3 | 7 Units of red blood cell STANDARD_DEVIATION 2.2 |
| Reticulocytes | 0.096 cells*10^6/uL | 0.071 cells*10^6/uL | 0.067 cells*10^6/uL |
| Reticulocytes/erythrocytes | 3.5 % | 2.4 % | 2.2 % |
| Serum iron | 96.0 ug/dL | 119.0 ug/dL | 127.0 ug/dL |
| Sex: Female, Male Female | 6 Participants | 15 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 26 Participants | 18 Participants |
| Soluble transferrin receptor | 2.5 mg/L | 1.6 mg/L | 1.3 mg/L |
| Spleen Volume | 2132.2 cm^3 STANDARD_DEVIATION 1439.5 | 2057.1 cm^3 STANDARD_DEVIATION 1299.8 | 2018.1 cm^3 STANDARD_DEVIATION 1248.5 |
| Total iron binding capacity | 214.5 ug/dL | 205.0 ug/dL | 201.0 ug/dL |
| Total Symptom Score | 19.00 units on a scale STANDARD_DEVIATION 16.14 | 20.73 units on a scale STANDARD_DEVIATION 14.65 | 21.73 units on a scale STANDARD_DEVIATION 13.97 |
| Transferrin saturation | 43.0 % | 53.0 % | 56.5 % |
| Unsaturated iron binding capacity | 113.5 ug/dL | 92.0 ug/dL | 81.0 ug/dL |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 41 |
| other Total, other adverse events | 36 / 41 |
| serious Total, serious adverse events | 14 / 41 |
Outcome results
Primary
Transfusion Independence Response by Week 24
The percentage of subjects who became transfusion independent for ≥ 12 weeks at any time on study. A subject was considered transfusion independent on study if no RBC transfusion occurred in any 12-week period during the 24-week treatment period.
Time frame: From baseline to Week 24
Population: Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that 6 subjects discontinued prior to Week 12 and could not be evaluated over the minimum period required for assessment of the endpoint (12 weeks).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total | Transfusion Independence Response by Week 24 | 34.1 percentage of subjects |
Secondary
Change in Inflammatory Markers - C-Reactive Protein (CRP)
Percent change in C-reactive protein at Weeks 2, 12 and 24. The baseline C-reactive protein value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 12 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 24 | -59.8 % Change from baseline |
| Total | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 12 | -67.8 % Change from baseline |
| Total | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 2 | -68.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 24 | -47.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 12 | -43.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 2 | -53.7 % Change from baseline |
| Total | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 24 | -54.8 % Change from baseline |
| Total | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 12 | -48.9 % Change from baseline |
| Total | Change in Inflammatory Markers - C-Reactive Protein (CRP) | Week 2 | -55.6 % Change from baseline |
Secondary
Change in Liver Iron Content
Percent change from baseline in liver iron content assessed by MRI. The baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: Measured at Week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Total | Change in Liver Iron Content | 4.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Liver Iron Content | 53.3 % Change from baseline |
| Total | Change in Liver Iron Content | 22.3 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Blasts
Change from baseline in % blasts at Weeks 2 and 4. The baseline % blasts value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2 and 4
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Blasts | Week 2 | 0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Blasts | Week 4 | 0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Blasts | Week 2 | 3.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Blasts | Week 4 | 1.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Blasts | Week 2 | 3.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Blasts | Week 4 | 1.0 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change
Hepcidin daily change (in nM) was calculated as the predose value subtracted from the 6 hours postdose value at each study visit. Daily hepcidin change at the baseline visit was the difference between 2 values obtained 6 hours apart. No momelotinib was administered on that day.
Time frame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 4 | -2.6 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 24 | -1.0 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 12 | -1.4 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 8 | -2.9 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Baseline | -1.7 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 20 | 0.0 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 2 | -4.9 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Day 1 | -4.8 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 16 | -0.4 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 8 | -5.2 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Baseline | 0.1 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Day 1 | -11.2 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 2 | -6.7 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 4 | -7.4 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 12 | -5.7 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 16 | -4.3 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 20 | -7.8 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 24 | -1.8 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 2 | -6.3 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Baseline | 0.0 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 16 | -2.7 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Day 1 | -8.6 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 24 | -1.4 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 8 | -4.4 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 4 | -5.4 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 20 | -5.3 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change | Week 12 | -4.1 nM |
Secondary
Change in Markers of Iron Metabolism and Anemia - Erythrocytes
Percent change from baseline in erythrocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 4 | 6.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 16 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 12 | 3.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 2 | 5.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 24 | -8.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 20 | -3.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 8 | 3.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 12 | 3.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 2 | 3.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 4 | 3.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 8 | 0.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 16 | -6.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 20 | -3.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 24 | 3.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 16 | -2.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 4 | 3.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 24 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 20 | -3.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 12 | 3.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 8 | 3.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythrocytes | Week 2 | 3.4 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Erythropoietin
Percent change in erythropoietin at Weeks 8 and 20. The baseline erythropoietin value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 8 and 20
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Erythropoietin | Week 8 | -30.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythropoietin | Week 20 | -45.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythropoietin | Week 8 | -8.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Erythropoietin | Week 20 | 8.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythropoietin | Week 8 | -24.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Erythropoietin | Week 20 | -4.4 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Ferritin
Percent change from baseline in ferritin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 4 | 19.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 2 | 11.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 8 | 4.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 24 | -14.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 12 | -0.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 20 | 3.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 16 | 0.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 24 | 15.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 16 | 21.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 20 | 13.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 8 | 30.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 4 | 8.3 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 2 | 8.8 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 12 | 26.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 24 | 1.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 16 | 6.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 2 | 8.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 4 | 13.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 8 | 16.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 12 | 11.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Ferritin | Week 20 | 7.0 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Hematocrit
Percent change from baseline in hematocrit, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 4 | 7.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 16 | 5.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 12 | 7.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 2 | 8.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 24 | 8.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 20 | 7.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 8 | 11.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 12 | 1.8 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 2 | 4.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 4 | 0.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 8 | -1.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 16 | -4.2 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 20 | 0.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 24 | 2.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 16 | 3.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 4 | 3.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 24 | 4.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 20 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 12 | 3.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 8 | 4.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hematocrit | Week 2 | 4.5 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Hemoglobin
Percent change from baseline in hemoglobin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 4 | 8.3 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 16 | 12.3 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 12 | 15.6 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 2 | 12.8 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 24 | 10.0 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 20 | 13.1 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 8 | 12.4 % Change in from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 12 | 4.5 % Change in from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 2 | 9.2 % Change in from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 4 | 6.3 % Change in from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 8 | 0.4 % Change in from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 16 | 0.6 % Change in from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 20 | 6.9 % Change in from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 24 | 5.8 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 16 | 10.2 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 4 | 6.9 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 24 | 7.9 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 20 | 7.4 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 12 | 7.5 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 8 | 5.6 % Change in from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Hemoglobin | Week 2 | 9.9 % Change in from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Leukocytes
Percent change from baseline in leukocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 24 | 53.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 2 | 11.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 4 | 6.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 8 | 34.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 12 | 8.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 16 | 42.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 20 | 44.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 12 | -15.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 20 | -27.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 2 | -24.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 8 | -0.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 16 | -6.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 4 | -4.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 24 | 18.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 4 | 0.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 8 | 8.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 20 | 16.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 12 | 5.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 24 | 27.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 2 | -14.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Leukocytes | Week 16 | 15.2 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Platelets
Percent change from baseline in platelets, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 2 | 21.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 24 | 38.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 12 | 24.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 20 | 31.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 4 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 16 | 17.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 8 | 19.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 16 | -26.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 20 | -36.2 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 24 | -22.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 8 | -33.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 2 | -24.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 12 | -27.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 4 | -29.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 24 | -15.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 4 | -26.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 8 | -12.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 12 | -11.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 16 | -6.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 20 | -14.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Platelets | Week 2 | -9.5 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Reticulocytes
Percent change from baseline in reticulocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 4 | 11.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 16 | 31.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 12 | 15.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 2 | 33.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 24 | 29.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 20 | 34.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 8 | 30.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 12 | -9.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 2 | -9.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 4 | 5.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 8 | -16.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 16 | 8.8 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 20 | 7.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 24 | -0.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 16 | 18.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 4 | 7.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 24 | 24.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 20 | 16.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 12 | 4.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 8 | 15.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes | Week 2 | 2.9 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes%
Percent change from baseline in reticulocytes/erythrocytes%, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 4 | 8.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 16 | 4.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 12 | 3.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 2 | 30.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 24 | 2.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 20 | 2.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 8 | 12.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 12 | 0.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 2 | -16.3 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 4 | 1.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 8 | -11.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 16 | 18.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 20 | 14.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 24 | -7.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 16 | 7.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 4 | 4.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 24 | -2.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 20 | 11.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 12 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 8 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% | Week 2 | -8.0 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Serum Iron
Percent change from baseline in serum iron, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 4 | 39.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 16 | -15.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 12 | 3.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 2 | 4.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 24 | -8.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 20 | -11.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 8 | 9.3 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 12 | 14.3 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 2 | 5.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 4 | 5.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 8 | 5.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 16 | 16.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 20 | 9.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 24 | -5.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 16 | 8.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 4 | 13.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 24 | -6.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 20 | 1.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 12 | 12.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 8 | 6.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Serum Iron | Week 2 | 5.9 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor
Percent change from baseline in soluble transferrin receptor, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 4 | -1.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 16 | -0.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 12 | 0.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 2 | 4.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 24 | -3.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 20 | -1.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 8 | 6.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 12 | 11.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 2 | -4.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 4 | 8.8 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 8 | 11.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 16 | 14.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 20 | -0.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 24 | 19.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 16 | 1.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 4 | 0.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 24 | -1.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 20 | -1.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 12 | 10.7 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 8 | 7.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor | Week 2 | -4.8 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity
Percent change from baseline in total iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 12 | 6.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 8 | 4.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 24 | 7.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 20 | 15.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 2 | 4.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 16 | 4.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 4 | 6.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 16 | 1.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 20 | 5.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 24 | 0.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 4 | 1.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 8 | 0.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 12 | 2.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 2 | 2.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 24 | 5.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 8 | 2.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 2 | 2.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 12 | 6.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 16 | 3.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 20 | 10.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity | Week 4 | 2.2 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation
Percent change from baseline in transferrin saturation, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 4 | 36.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 16 | -7.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 12 | 11.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 2 | 2.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 24 | -8.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 20 | -2.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 8 | 9.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 12 | 16.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 2 | 13.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 4 | 9.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 8 | -5.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 16 | -13.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 20 | -20.8 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 24 | -20.8 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 16 | -10.4 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 4 | 10.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 24 | -11.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 20 | -13.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 12 | 14.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 8 | -3.1 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation | Week 2 | 10.3 % Change from baseline |
Secondary
Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin
Median hepcidin at trough was assessed predose at each study visit.
Time frame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 4 | 19.8 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 24 | 15.5 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 12 | 21.3 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 8 | 16.6 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Baseline | 22.0 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 20 | 13.4 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 2 | 25.1 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Day 1 | 19.7 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 16 | 16.9 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 8 | 51.7 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Baseline | 42.4 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Day 1 | 43.7 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 2 | 52.1 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 4 | 46.4 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 12 | 44.7 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 16 | 51.9 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 20 | 44.2 nM |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 24 | 51.5 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 2 | 38.4 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Baseline | 36.6 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 16 | 34.5 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Day 1 | 36.5 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 24 | 28.4 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 8 | 35.5 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 4 | 37.6 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 20 | 27.5 nM |
| Total | Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin | Week 12 | 30.4 nM |
Secondary
Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity
Percent change from baseline in unsaturated iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
Time frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 4 | -4.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 16 | 4.3 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 12 | 2.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 2 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 24 | 12.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 20 | 16.5 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 8 | 6.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 12 | -18.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 2 | -5.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 4 | 0.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 8 | 0.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 16 | 0.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 20 | 5.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 24 | 6.9 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 16 | 2.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 4 | -1.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 24 | 12.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 20 | 14.2 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 12 | -1.6 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 8 | 0.0 % Change from baseline |
| Total | Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity | Week 2 | 0.0 % Change from baseline |
Secondary
Change in Pharmacodynamics Biomarker - pSTAT3
Percent change in %pSTAT stimulated CD3+/4+ T cell at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
Time frame: On Day 1 and at Weeks 4 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 4 hours postdose | -17.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 4 hours postdose | -30.6 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 6 hours postdose | -12.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 6 hours postdose | -9.0 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 6 hours postdose | -17.0 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 2 hours postdose | -18.9 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - predose | -0.9 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 4 hours postdose | -19.8 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 2 hours postdose | -15.8 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 2 hours postdose | -31.2 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - predose | -4.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 6 hours postdose | -10.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - predose | -2.9 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 2 hours postdose | -20.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 2 hours postdose | -10.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 4 hours postdose | -14.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 2 hours postdose | -13.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 4 hours postdose | -10.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 6 hours postdose | -4.3 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 4 hours postdose | -14.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 6 hours postdose | -9.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - predose | -0.3 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 4 hours postdose | -12.8 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 6 hours postdose | -9.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 2 hours postdose | -20.0 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 6 hours postdose | -7.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - 4 hours postdose | -14.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 4 hours postdose | -22.6 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 6 hours postdose | -13.4 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 4 - predose | -2.0 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Day 1 - 2 hours postdose | -14.3 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - 2 hours postdose | -22.7 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3 | Week 24 - predose | -2.8 % Change from baseline |
Secondary
Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio
Percent change in %pSTAT/%tSTAT Stimulated CD3+/4+ T cell ratio at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
Time frame: On Day 1 and at Weeks 4 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 4 hours postdose | -21.4 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 4 hours postdose | -9.6 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 2 hours postdose | -14.3 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 6 hours postdose | -9.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 2 hours postdose | -13.2 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 4 hours postdose | 3.0 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 6 hours postdose | -18.4 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 6 hours postdose | 12.5 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 2 hours postdose | -18.7 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - predose | 0.5 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - predose | -5.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - predose | 5.0 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 2 hours postdose | -7.6 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 6 hours postdose | -3.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 4 hours postdose | -11.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 6 hours postdose | -6.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - predose | -3.5 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 2 hours postdose | -9.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 4 hours postdose | -9.7 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 4 hours postdose | -13.4 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 6 hours postdose | -6.1 % Change from baseline |
| Transfusion Independence Non-Responders | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 2 hours postdose | -15.5 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 6 hours postdose | -11.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 2 hours postdose | -13.4 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 4 hours postdose | -9.7 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Day 1 - 6 hours postdose | -4.6 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - predose | 4.8 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 2 hours postdose | -13.2 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 6 hours postdose | -6.1 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - predose | -4.4 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 2 hours postdose | -16.2 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 24 - 4 hours postdose | -15.4 % Change from baseline |
| Total | Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio | Week 4 - 4 hours postdose | -13.4 % Change from baseline |
Secondary
Response Rate in Total Symptom Score (TSS) at Week 24
The percentage of subjects achieving a ≥ 50% reduction from baseline in TSS at Week 24, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) diary. Total symptom score was assessed using the modified MPN-SAF TSS Version 2, an 8-item questionnaire developed to assess symptom burden and quality of life in patients with MPN. The modified MPN-SAF TSS contained 8 questions, 7 of which were summed to generate the score (the included questions related to tiredness, early satiety, abdominal discomfort, night sweats, itching, bone pain, and pain under the ribs on the left side). Each question is scored on a scale of 0-10, where higher numbers indicate more severe symptoms. For this study, the TSS scale ranges from 0 to 70. The questionnaire was completed daily on an electronic diary device.
Time frame: Measured at Week 24
Population: There were 3 subjects with missing TSS at baseline who were excluded from the analysis. Note that of the 38 subjects evaluated, 17 were missing Week 24 TSS assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total | Response Rate in Total Symptom Score (TSS) at Week 24 | 15.8 percentage of subjects |
Secondary
Splenic Response Rate at Week 24
The percentage of subjects who achieved a ≥ 35% reduction in spleen volume from baseline as measured by MRI at Week 24.
Time frame: Measured at Week 24
Population: Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that spleen volume at Week 24 was not available for 15 subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total | Splenic Response Rate at Week 24 | 12.2 percentage of subjects |
Secondary
Transfusion Response Rate by Week 24
The percentage of subjects who became transfusion independent for ≥ 8 weeks, defined as no RBC transfusions for at least an 8-week period at any time on study.
Time frame: From baseline to Week 24
Population: Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that 3 subjects discontinued prior to Week 8 and could not be evaluated over the minimum period required for assessment of the endpoint (8 weeks).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total | Transfusion Response Rate by Week 24 | 39.0 percentage of subjects |