MPN (Myeloproliferative Neoplasms)
Conditions
Keywords
PMF, PPV-MF, PET-MF
Brief summary
To evaluate the effects of treatment with ruxolitinib (INCB018424) on spleen volume, symptoms and potential side effects in participants with PMF, PPV-MF and PET-MF who have platelet counts of 50 x 10\^9/L to 100 x 10\^9/L. It is anticipated that individualized dose optimization from the starting ruxolitinib level of 5 mg bid will be associated with reductions in splenomegaly, MF-associated symptoms and inflammatory cytokine levels.
Interventions
DRUGRuxolitinib
Ruxolitinib (INCB018424), 5 mg bid
Sponsors
Incyte Corporation
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
* Diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy * Discontinuation of all drugs used to treat underlying MF disease at least 14 days prior to baseline visit * INR \<= 1.5 or PTT value \< 1.5 x upper limit of normal (ULN) at study entry * Hemoglobin level at least 6.5 g/dL at Screening visit * Willingness to be transfused to treat low hemoglobin levels
Exclusion criteria
* Females who are pregnant, unable to comply with birth control use to avoid becoming pregnant or breastfeeding * Males who cannot comply with birth control use to avoid fathering a child * Platelet count \< 50 x10\^9/L or absolute neutrophil count (ANC) \< 1 x10\^9/L at the Screening visit * Inadequate liver or renal function; Intracranial bleeds or invasive malignancy over the previous 2 years - international normalized ratio (INR) laboratory values cannot be \> 1.5 x upper limit of normal at study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose | Baseline and Week 24 | Magnetic resonance imaging (MRI) of the upper and lower abdomen and pelvis was performed to assess spleen volumes. Computed tomography (CT) scan was performed if participant was not a candidate for MRI or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose | Baseline and Week 24 | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms. |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | Up to Week 156 | TEAE was defined as adverse events that began or worsened from baseline after the first administration of the study drug. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred. |
| Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) | Up to Week 156 | Participants with platelet count between 50 and 100 × 10\^9/L at the screening and/or baseline visit were enrolled in the study. Thrombocytopenia is defined as a condition with low blood platelet count. Grade 4 thrombocytopenia was platelet count \< 25 × 10\^9/L. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred. |
| Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 | Up to Week 156 | Hemorrhages were defined as any lower level terms by MedDRA included in the Standardized MedDRA Query (SMQ) for hemorrhage terms. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Spleen Length Measured by Palpation | Up to Week 156 | Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion. |
| Percent Change in Spleen Volume at Week 24 Compared to Baseline | Baseline and Week 24 | MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant was not a candidate for MRI, or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Patient Global Impression of Change (PGIC) Score at Each Visit | Up to Week 156 | Symptoms of myelofibrosis were assessed using the PGIC questionnaire. Using the questionnaire, patients rated the overall sense of treatment effect on their symptoms on a scale of 1 (very much improved)- 7(very much worse). The specific wording was: Since the start of the treatment you've received in this study, your myelofibrosis symptoms are: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse. A higher score indicates worse symptoms. |
| Percent Change From Baseline in Spleen Length Measured by Palpation | Up to Week 156 | Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion. |
| Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline | Baseline and Week 24 | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.. |
| Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline | Baseline and Week 24 | MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline | Baseline and Week 24 | MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline | Baseline and Week 24 | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 27 investigative sites in the United States from 15 June 2011 to 19 December 2018.
Pre-assignment details
A total of 66 participants were enrolled in the study. Fifty-five participants completed 24 weeks of treatment (core treatment period), and 23 participants entered the extension phase.
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib 5 mg Doses may not exceed 10 mg bid except in subjects who continue to meet the above dose escalation criteria, and who have, in addition, a PGIC score of minimally worse, much worse or very much worse while receiving 10 mg bid. Such subjects may continue dose escalation to a maximum dose of 15 mg bid.
During the extended treatment phase, doses of ruxolitinib may be increased in 5 mg qd increments up to a dose of 25 mg bid if the subject meets the above dose escalation criteria, or per the investigator's discretion. | 66 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Consent withdrawn | 7 |
| Overall Study | Death | 1 |
| Overall Study | Disease progression | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other Unspecified | 8 |
| Overall Study | Termination of clinical trial by sponsor | 1 |
Baseline characteristics
| Characteristic | Ruxolitinib 5 mg |
|---|---|
| Age, Continuous | 68.7 years STANDARD_DEVIATION 9.44 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 3 Participants |
| Race/Ethnicity, Customized Ethnicity Non-Hispanic or Non-Latino | 63 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 4 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants |
| Race/Ethnicity, Customized Race White | 58 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 66 | 0 / 54 | 2 / 44 | 0 / 9 |
| other Total, other adverse events | 13 / 15 | 43 / 66 | 26 / 54 | 31 / 44 | 5 / 9 |
| serious Total, serious adverse events | 5 / 15 | 8 / 66 | 4 / 54 | 9 / 44 | 1 / 9 |
Outcome results
Primary
Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03
Hemorrhages were defined as any lower level terms by MedDRA included in the Standardized MedDRA Query (SMQ) for hemorrhage terms. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Time frame: Up to Week 156
Population: Safety evaluable population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg QD or 5 mg BID | Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 | 6.7 percentage of participants |
| 5 mg AM/ 10 mg PM | Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 | 3.0 percentage of participants |
| 10 mg BID | Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 | 1.9 percentage of participants |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 | 2.3 percentage of participants |
| >20 mg | Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 | 11.1 percentage of participants |
Primary
Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03)
Participants with platelet count between 50 and 100 × 10\^9/L at the screening and/or baseline visit were enrolled in the study. Thrombocytopenia is defined as a condition with low blood platelet count. Grade 4 thrombocytopenia was platelet count \< 25 × 10\^9/L. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Time frame: Up to Week 156
Population: Safety evaluable population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg QD or 5 mg BID | Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) | 23.1 percentage of participants |
| 5 mg AM/ 10 mg PM | Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) | 3.0 percentage of participants |
| 10 mg BID | Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) | 5.7 percentage of participants |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) | 4.7 percentage of participants |
| >20 mg | Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) | 0.0 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAE)
TEAE was defined as adverse events that began or worsened from baseline after the first administration of the study drug. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Time frame: Up to Week 156
Population: Safety evaluable population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg QD or 5 mg BID | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | 93.3 percentage of participants |
| 5 mg AM/ 10 mg PM | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | 74.2 percentage of participants |
| 10 mg BID | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | 61.1 percentage of participants |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | 77.3 percentage of participants |
| >20 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | 55.6 percentage of participants |
Primary
Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose
Magnetic resonance imaging (MRI) of the upper and lower abdomen and pelvis was performed to assess spleen volumes. Computed tomography (CT) scan was performed if participant was not a candidate for MRI or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time frame: Baseline and Week 24
Population: Intent-to-treat (ITT) population included all participants enrolled and treated in the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose | -11.6 Percentage change from baseline | Standard Deviation 18.68 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose | -17.4 Percentage change from baseline | Standard Deviation 0.63 |
| 10 mg BID | Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose | -22.4 Percentage change from baseline | Standard Deviation 22.86 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose | -13.4 Percentage change from baseline | Standard Deviation 22.29 |
p-value: 0.025t-test, 1 sided
p-value: 0.0163t-test, 1 sided
p-value: <0.0001t-test, 1 sided
p-value: 0.2019t-test, 1 sided
Primary
Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Time frame: Baseline and Week 24
Population: ITT population included all participants enrolled and treated in the study. For the 5 mg AM/ 10 mg PM arm, the t-test was not calculated due to only having a single participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose | -6.35 Percentage change from baseline | Standard Deviation 64.207 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose | -39.51 Percentage change from baseline | — |
| 10 mg BID | Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose | -47.54 Percentage change from baseline | Standard Deviation 46.886 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose | 7.95 Percentage change from baseline | Standard Deviation 113.17 |
p-value: 0.6887t-test, 1 sided
p-value: <0.0001t-test, 1 sided
p-value: 0.8701t-test, 1 sided
Secondary
Change in Spleen Length Measured by Palpation
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Time frame: Up to Week 156
Population: Efficacy evaluable participants included all participants enrolled and treated in the study. 'Number Analyzed' is number of participants with data available at a particular time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 12 | -4.53 cm | Standard Deviation 4.812 |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 84 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 24 | -4.25 cm | Standard Deviation 5.092 |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 20 | -4.56 cm | Standard Deviation 4.844 |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 16 | -3.79 cm | Standard Deviation 4.973 |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 144 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 8 | -4.65 cm | Standard Deviation 3.558 |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Baseline | 11.48 cm | Standard Deviation 5.81 |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 156 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 108 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 96 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 4 | -3.40 cm | Standard Deviation 3.068 |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 132 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 72 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 60 | -7.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 120 | -4.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 48 | -7.00 cm | — |
| 5 mg QD or 5 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 36 | -7.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 24 | -7.00 cm | Standard Deviation 5.657 |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Baseline | 14.00 cm | Standard Deviation 4.359 |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 4 | -4.00 cm | Standard Deviation 6.083 |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 8 | -5.33 cm | Standard Deviation 4.933 |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 12 | -6.50 cm | Standard Deviation 3.536 |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 16 | -4.50 cm | Standard Deviation 3.536 |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 20 | -7.50 cm | Standard Deviation 4.95 |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 36 | -11.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 48 | -11.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 132 | -5.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 60 | -11.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 72 | -11.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 96 | -8.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 108 | -10.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 120 | -6.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 144 | -3.00 cm | — |
| 5 mg AM/ 10 mg PM | Change in Spleen Length Measured by Palpation | Change at Week 156 | -3.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 8 | -2.81 cm | Standard Deviation 3.514 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 48 | -2.33 cm | Standard Deviation 2.517 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 132 | 1.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 72 | -1.50 cm | Standard Deviation 2.121 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 84 | -3.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 156 | 0.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 96 | 0.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Baseline | 13.13 cm | Standard Deviation 8.241 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 144 | 0.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 16 | -3.69 cm | Standard Deviation 4.343 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 108 | 0.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 20 | -5.28 cm | Standard Deviation 5.567 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 12 | -3.74 cm | Standard Deviation 5.118 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 24 | -4.57 cm | Standard Deviation 5.541 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 120 | 2.00 cm | — |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 36 | -2.75 cm | Standard Deviation 3.862 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 60 | -2.67 cm | Standard Deviation 2.517 |
| 10 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 4 | -1.84 cm | Standard Deviation 3.195 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 48 | 0.00 cm | Standard Deviation 0 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Baseline | 14.71 cm | Standard Deviation 6.726 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 4 | 0.00 cm | Standard Deviation 3.688 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 12 | -3.71 cm | Standard Deviation 7.544 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 24 | -1.33 cm | Standard Deviation 3.983 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 60 | 1.50 cm | Standard Deviation 2.121 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 8 | -1.14 cm | Standard Deviation 2.34 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 20 | -3.50 cm | Standard Deviation 7.064 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 36 | 1.00 cm | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 72 | 1.00 cm | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 16 | -2.00 cm | Standard Deviation 2.449 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Change in Spleen Length Measured by Palpation | Change at Week 84 | -2.00 cm | — |
Secondary
Patient Global Impression of Change (PGIC) Score at Each Visit
Symptoms of myelofibrosis were assessed using the PGIC questionnaire. Using the questionnaire, patients rated the overall sense of treatment effect on their symptoms on a scale of 1 (very much improved)- 7(very much worse). The specific wording was: Since the start of the treatment you've received in this study, your myelofibrosis symptoms are: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse. A higher score indicates worse symptoms.
Time frame: Up to Week 156
Population: Efficacy evaluable participants included all participants enrolled and treated in the study. 'Number Analyzed' is number of participants with data available at the particular time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 36 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 60 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 24 | 2.9 score on a scale | Standard Deviation 1.27 |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 20 | 2.4 score on a scale | Standard Deviation 0.86 |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 132 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 8 | 2.7 score on a scale | Standard Deviation 1.22 |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 4 | 2.8 score on a scale | Standard Deviation 0.89 |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 120 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 108 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 12 | 2.4 score on a scale | Standard Deviation 0.96 |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 144 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 96 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 72 | 2.0 score on a scale | — |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 16 | 2.4 score on a scale | Standard Deviation 0.83 |
| 5 mg QD or 5 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 156 | 2.0 score on a scale | — |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 16 | 2.0 score on a scale | Standard Deviation 1 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 4 | 2.8 score on a scale | Standard Deviation 1.26 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 8 | 2.3 score on a scale | Standard Deviation 0.96 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 12 | 2.3 score on a scale | Standard Deviation 1.15 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 20 | 2.3 score on a scale | Standard Deviation 0.58 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 24 | 2.3 score on a scale | Standard Deviation 0.58 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 36 | 3.0 score on a scale | — |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 48 | 2.5 score on a scale | Standard Deviation 0.71 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 60 | 2.5 score on a scale | Standard Deviation 0.71 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 72 | 2.5 score on a scale | Standard Deviation 0.71 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 84 | 2.0 score on a scale | — |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 96 | 2.5 score on a scale | Standard Deviation 0.71 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 108 | 2.5 score on a scale | Standard Deviation 0.71 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 120 | 2.5 score on a scale | Standard Deviation 0.71 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 132 | 3.0 score on a scale | Standard Deviation 1.41 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 144 | 2.5 score on a scale | Standard Deviation 0.71 |
| 5 mg AM/ 10 mg PM | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 156 | 3.0 score on a scale | Standard Deviation 1.41 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 144 | 1.0 score on a scale | — |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 84 | 1.0 score on a scale | Standard Deviation 0 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 4 | 2.6 score on a scale | Standard Deviation 1.09 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 24 | 1.9 score on a scale | Standard Deviation 0.98 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 156 | 1.0 score on a scale | — |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 108 | 1.0 score on a scale | — |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 36 | 1.8 score on a scale | Standard Deviation 0.5 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 12 | 2.2 score on a scale | Standard Deviation 1.17 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 8 | 2.2 score on a scale | Standard Deviation 0.99 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 48 | 1.3 score on a scale | Standard Deviation 0.58 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 16 | 1.9 score on a scale | Standard Deviation 0.91 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 132 | 1.0 score on a scale | — |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 60 | 1.7 score on a scale | Standard Deviation 0.58 |
| 10 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 20 | 1.9 score on a scale | Standard Deviation 1.11 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 48 | 2.0 score on a scale | Standard Deviation 0 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 60 | 3.0 score on a scale | Standard Deviation 0 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 12 | 3.4 score on a scale | Standard Deviation 1.27 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 4 | 3.3 score on a scale | Standard Deviation 0.76 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 72 | 4.0 score on a scale | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 84 | 3.0 score on a scale | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 8 | 2.9 score on a scale | Standard Deviation 0.69 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 20 | 2.3 score on a scale | Standard Deviation 0.82 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 16 | 3.3 score on a scale | Standard Deviation 0.95 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 24 | 2.0 score on a scale | Standard Deviation 1 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Patient Global Impression of Change (PGIC) Score at Each Visit | Week 36 | 2.5 score on a scale | Standard Deviation 0.71 |
Secondary
Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time frame: Baseline and Week 24
Population: Efficacy evaluable participants included all participants enrolled and treated in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg QD or 5 mg BID | Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline | 42.9 percentage of participants |
| 5 mg AM/ 10 mg PM | Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline | 66.7 percentage of participants |
| 10 mg BID | Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline | 63.6 percentage of participants |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline | 28.6 percentage of participants |
Secondary
Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time frame: Baseline and Week 24
Population: Efficacy evaluable participants included all participants enrolled and treated in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg QD or 5 mg BID | Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline | 4.8 percentage of participants |
| 5 mg AM/ 10 mg PM | Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline | 0.0 percentage of participants |
| 10 mg BID | Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline | 24.2 percentage of participants |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline | 28.6 percentage of participants |
Secondary
Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Time frame: Baseline and Week 24
Population: Efficacy evaluable participants included all participants enrolled and treated in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg QD or 5 mg BID | Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline | 28.6 percentage of participants |
| 5 mg AM/ 10 mg PM | Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline | 0.0 percentage of participants |
| 10 mg BID | Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline | 44.1 percentage of participants |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline | 28.6 percentage of participants |
Secondary
Percent Change From Baseline in Spleen Length Measured by Palpation
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Time frame: Up to Week 156
Population: Efficacy evaluable participants included all participants enrolled and treated in the study. 'Number Analyzed' is number of participants with data available at a particular time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 156 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 72 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 60 | -58.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 20 | -44.58 Percentage | Standard Deviation 46.49 |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 48 | -58.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 36 | -58.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 24 | -45.39 Percentage | Standard Deviation 53.913 |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 132 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 8 | -50.64 Percentage | Standard Deviation 39.93 |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 144 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 120 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 108 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 12 | -49.90 Percentage | Standard Deviation 48.623 |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 4 | -38.61 Percentage | Standard Deviation 36.532 |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 96 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 84 | -33.33 Percentage | — |
| 5 mg QD or 5 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 16 | -43.24 Percentage | Standard Deviation 48.173 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 20 | -56.60 Percentage | Standard Deviation 17.187 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 108 | -62.50 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 120 | -37.50 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 4 | -26.62 Percentage | Standard Deviation 36.906 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 8 | -37.95 Percentage | Standard Deviation 28.772 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 12 | -50.35 Percentage | Standard Deviation 8.348 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 16 | -32.99 Percentage | Standard Deviation 15.222 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 24 | -51.04 Percentage | Standard Deviation 25.043 |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 36 | -68.75 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 48 | -68.75 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 60 | -68.75 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 72 | -68.75 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 96 | -50.00 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 132 | -31.25 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 144 | -18.75 Percentage | — |
| 5 mg AM/ 10 mg PM | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 156 | -18.75 Percentage | — |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 8 | -28.32 Percentage | Standard Deviation 31.151 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 48 | -31.82 Percentage | Standard Deviation 19.285 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 16 | -38.67 Percentage | Standard Deviation 36.07 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 60 | -36.36 Percentage | Standard Deviation 12.856 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 72 | -27.27 Percentage | — |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 84 | -27.27 Percentage | — |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 12 | -38.21 Percentage | Standard Deviation 39.936 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 24 | -42.01 Percentage | Standard Deviation 36.899 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 20 | -48.06 Percentage | Standard Deviation 38.826 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 36 | -20.76 Percentage | Standard Deviation 27.637 |
| 10 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 4 | -21.88 Percentage | Standard Deviation 33.8 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 84 | -10.00 Percentage | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 36 | 5.00 Percentage | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 48 | 0.00 Percentage | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 16 | -14.33 Percentage | Standard Deviation 14.903 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 4 | -1.42 Percentage | Standard Deviation 22.902 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 20 | -27.75 Percentage | Standard Deviation 39.024 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 60 | 15.00 Percentage | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 8 | -8.72 Percentage | Standard Deviation 13.991 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 72 | 5.00 Percentage | — |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 12 | -22.41 Percentage | Standard Deviation 40.833 |
| 10 mg AM/ 15 mg PM or 15 mg BID | Percent Change From Baseline in Spleen Length Measured by Palpation | Percent Change at Week 24 | -9.89 Percentage | Standard Deviation 25.001 |
Secondary
Percent Change in Spleen Volume at Week 24 Compared to Baseline
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant was not a candidate for MRI, or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time frame: Baseline and Week 24
Population: ITT population included all participants enrolled and treated in the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg QD or 5 mg BID | Percent Change in Spleen Volume at Week 24 Compared to Baseline | -17.8 Percentage | Standard Deviation 21.27 |
p-value: <0.0001t-test, 1 sided
Secondary
Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms..
Time frame: Baseline and Week 24
Population: ITT population included all participants enrolled and treated in the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg QD or 5 mg BID | Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline | -27.90 Percentage change from baseline | Standard Deviation 64.818 |
p-value: 0.0028t-test, 1 sided