Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Post Polycythemia Vera Myelofibrosis, Primary Myelofibrosis
Conditions
Keywords
INCB050465, ruxolitinib, parsaclisib, LIMBER, MF, Myelofibrosis, Myeloproliferative Neoplasms, Myoproliferative Neoplasms
Brief summary
The purpose of the study is to compare the efficacy of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis.
Detailed description
This is a Phase 3, randomized, double-blind study of the combination of the PI3Kδ inhibitor parsaclisib or matching placebo and the JAK1/2 inhibitor ruxolitinib in participants with PMF or secondary MF (PPV-MF or PET-MF) with DIPSS risk category of intermediate or high. Prospective participants must have not received prior MF therapy with a JAK inhibitor or a PI3K inhibitor. After participants have been determined to be eligible for the study and completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2 treatment groups, with stratification for platelet count (≥ 100 × 10\^9/L vs 50 to \< 100 × 10\^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs intermediate-1). Once all enrolled participants completed the week 24 assessments the study will be unblinded and and participants randomized to placebo will have the opportunity to cross over to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.
Interventions
DRUGparsaclisib
parsaclisib will be administered QD orally
DRUGruxolitinib
ruxolitinib will be administered BID orally
DRUGplacebo
placebo will be administered QD orally
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Triple blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of PMF, PPV-MF, or PET-MF. * DIPSS risk category of intermediate-1, intermediate-2, or high. * Palpable spleen of ≥ 5 cm below the left costal margin on physical examination at the screening visit. * Active symptoms of MF at the screening visit, as demonstrated by the presence of a TSS of ≥ 10 using the Screening Symptom Form. * Participants with an ECOG performance status score of 0, 1, or 2. * Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF. * Life expectancy of at least 24 weeks. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* Prior use of any JAK inhibitor. * Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib). * Use of experimental drug therapy for MF or any other standard drug (eg, danazol, hydroxyurea) used for MF within 3 months of starting study drug and/or lack of recovery from all toxicities from previous therapy to ≤ Grade 1. * Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications. * Recent history of inadequate bone marrow reserve. * Inadequate liver and renal function at screening. * Active bacterial, fungal, parasitic, or viral infection that requires therapy. * Active HBV or HCV infection that requires treatment or at risk for HBV reactivation. * Known HIV infection. * Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol. * Active invasive malignancy over the previous 2 years. * Splenic irradiation within 6 months before receiving the first dose of study drug. * Concurrent use of any prohibited medications. * Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements. * Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study. * Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy. * Currently breastfeeding or pregnant. * Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. * History of Grade 3 or 4 irAEs from prior immunotherapy. * Receipt of any live vaccine within 30 days of the first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥35% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging [MRI] (or Computed Tomography [CT] Scan in Applicable Participants) | Baseline; Week 24 | Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available. Determination of spleen length below the left costal margin was measured by palpation, using a flexible ruler provided by the sponsor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary | Baseline; Week 24 | Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary | Baseline; up to Week 24 | Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores. |
| Overall Survival | up to 749 days | Overall survival was defined as the interval between the randomization date and the date of death due to any cause. |
| Percentage of Participants Who Had a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v4.0 (MFSAF v4.0) Diary | Baseline; Week 24 | Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores. |
| Number of Participants With Any Grade 3 or Higher TEAE | up to 960 days | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 to 35 days after the last dose of parsaclisib/matching placebo or ruxolitinib. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting instrumental activities of daily living (ADL). Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: life-threatening urgent intervention indicated. Grade 5: death related to AE. |
| Time of Onset of a ≥35% Reduction in Spleen Volume | up to 925 days | The time to the first ≥35% reduction in spleen volume is defined as the time from randomization to the first time participants had ≥35% reduction in spleen volume. |
| Duration of Maintenance of a ≥35% Reduction in Spleen Volume | up to 925 days | The duration of ≥35% reduction from Baseline in spleen volume was defined as the interval between the first spleen volume measurement that was a ≥35% reduction from Baseline and the date of the first measurement that was no longer a ≥35% reduction from Baseline. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to 960 days | An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 to 35 days after the last dose of parsaclisib/matching placebo or ruxolitinib. |
Countries
Austria, Belgium, China, Denmark, Finland, France, Germany, Israel, Italy, Japan, Norway, Poland, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
This study was conducted at 93 study sites in Austria, Belgium, China, Denmark, Finland, France, Germany, Israel, Italy, Japan, Norway, Poland, South Korea, Spain, Turkey, the United Kingdom, and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Parsaclisib Plus Ruxolitinib Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1 and continued on this regimen as long as it was tolerated and the participants did not meet any discontinuation criteria. Participants with a Baseline platelet count ≥100 × 10\^9/Liter received ruxolitinib 15 milligrams (mg) twice daily (BID). Participants with a Baseline platelet count of 50 to \< 100 × 10\^9/Liters inclusive received ruxolitinib 5 mg BID. Participants were also stratified according to the Dynamic International Prognostic Scoring System (DIPSS) risk category (high versus intermediate-2 versus intermediate-1). Participants received parsaclisib at a dose of 5 mg once daily (QD). | 125 |
| Placebo Plus Ruxolitinib Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continued on this regimen until they left the study. Participants with a Baseline platelet count ≥100 × 10\^9/Liter received ruxolitinib 15 mg BID. Participants with a Baseline platelet count of 50 to \< 100 × 10\^9/Liters inclusive received ruxolitinib 5 mg BID. Participants were also stratified according to the DIPSS risk category (high versus intermediate-2 versus intermediate-1). Participants received matching placebo at a dose of 5 mg QD. After 24 weeks, participants randomized to receive placebo plus ruxolitinib could have switched to treatment with parsaclisib plus ruxolitinib per the regimen received during the first 24 weeks of the study. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. | 127 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Awaiting Rollover to Another Study to Receive Ruxolitinib | 2 | 3 |
| Overall Study | Concomitant Diagnosis of Mature Plasmacytoid Dendritic Cell Proliferation | 0 | 1 |
| Overall Study | Death | 5 | 3 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Sponsor Decision | 104 | 117 |
| Overall Study | Withdrawal by Subject | 8 | 2 |
Baseline characteristics
| Characteristic | Placebo Plus Ruxolitinib | Total | Parsaclisib Plus Ruxolitinib |
|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 10.9 | 63.3 years STANDARD_DEVIATION 10.61 | 63.2 years STANDARD_DEVIATION 10.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 213 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 25 Participants | 15 Participants |
| Race/Ethnicity, Customized Asian | 31 Participants | 64 Participants | 33 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Captured as Not Hispanic, Latino or Spanish in Database | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Reported | 10 Participants | 20 Participants | 10 Participants |
| Race/Ethnicity, Customized Turkish | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White or Caucasian | 84 Participants | 164 Participants | 80 Participants |
| Sex: Female, Male Female | 49 Participants | 98 Participants | 49 Participants |
| Sex: Female, Male Male | 78 Participants | 154 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 125 | 3 / 127 |
| other Total, other adverse events | 109 / 125 | 109 / 127 |
| serious Total, serious adverse events | 26 / 125 | 18 / 127 |
Outcome results
Primary
Percentage of Participants Achieving ≥35% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging [MRI] (or Computed Tomography [CT] Scan in Applicable Participants)
Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available. Determination of spleen length below the left costal margin was measured by palpation, using a flexible ruler provided by the sponsor.
Time frame: Baseline; Week 24
Population: Intent-to-Treat (ITT) Population: all randomized participants. Treatment groups were defined according to the treatment assignment at randomization regardless of the actual study drug the participant took during their participation. Participants who had both Baseline and Week 24 measurements, or discontinued treatment before 27APR2023, or reached Week 24 before 27APR2023 but were missing Week 24 assessments were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Percentage of Participants Achieving ≥35% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging [MRI] (or Computed Tomography [CT] Scan in Applicable Participants) | 52.8 percentage of participants |
| Placebo Plus Ruxolitinib | Percentage of Participants Achieving ≥35% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging [MRI] (or Computed Tomography [CT] Scan in Applicable Participants) | 46.7 percentage of participants |
p-value: 0.422495% CI: [0.71, 2.26]Cochran-Mantel-Haenszel
Secondary
Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary
Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 24
Population: ITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Parsaclisib Plus Ruxolitinib | Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary | Baseline | 19.8 scores on a scale | Standard Deviation 14.29 |
| Parsaclisib Plus Ruxolitinib | Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary | Change from Baseline at Week 24 | -6.6 scores on a scale | Standard Deviation 12.36 |
| Placebo Plus Ruxolitinib | Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary | Baseline | 19.6 scores on a scale | Standard Deviation 13.07 |
| Placebo Plus Ruxolitinib | Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary | Change from Baseline at Week 24 | -6.8 scores on a scale | Standard Deviation 10.74 |
Secondary
Duration of Maintenance of a ≥35% Reduction in Spleen Volume
The duration of ≥35% reduction from Baseline in spleen volume was defined as the interval between the first spleen volume measurement that was a ≥35% reduction from Baseline and the date of the first measurement that was no longer a ≥35% reduction from Baseline.
Time frame: up to 925 days
Population: ITT Population. Participants with DIPSS risk level being low risk level (0 prognostic points) have been excluded from the analysis. Only those participants with a ≥35% reduction in spleen volume who then had a loss of ≥35% reduction in spleen volume with a 25% increase from NADIR were analyzed. If the maintenance end date was not observed before the database cutoff, the duration was censored at the last assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Duration of Maintenance of a ≥35% Reduction in Spleen Volume | 505.0 days |
| Placebo Plus Ruxolitinib | Duration of Maintenance of a ≥35% Reduction in Spleen Volume | NA days |
p-value: 0.6127Log Rank
Secondary
Number of Participants With Any Grade 3 or Higher TEAE
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 to 35 days after the last dose of parsaclisib/matching placebo or ruxolitinib. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting instrumental activities of daily living (ADL). Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: life-threatening urgent intervention indicated. Grade 5: death related to AE.
Time frame: up to 960 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Number of Participants With Any Grade 3 or Higher TEAE | 75 Participants |
| Placebo Plus Ruxolitinib | Number of Participants With Any Grade 3 or Higher TEAE | 75 Participants |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 to 35 days after the last dose of parsaclisib/matching placebo or ruxolitinib.
Time frame: up to 960 days
Population: Safety Population: all participants who received at least 1 dose of parsaclisib, placebo, or ruxolitinib. Treatment groups for this population were determined according to the actual treatment the participant received regardless of assigned study drug treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 117 Participants |
| Placebo Plus Ruxolitinib | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 119 Participants |
Secondary
Overall Survival
Overall survival was defined as the interval between the randomization date and the date of death due to any cause.
Time frame: up to 749 days
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Overall Survival | NA days |
| Placebo Plus Ruxolitinib | Overall Survival | NA days |
Secondary
Percentage of Participants Who Had a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v4.0 (MFSAF v4.0) Diary
Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores.
Time frame: Baseline; Week 24
Population: ITT Population. Participants who had both Baseline and Week 24 measurements, or discontinued treatment before 27APR2023, or reached Week 24 before 27APR2023 but were missing Week 24 assessments were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Percentage of Participants Who Had a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v4.0 (MFSAF v4.0) Diary | 34.8 percentage of participants |
| Placebo Plus Ruxolitinib | Percentage of Participants Who Had a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v4.0 (MFSAF v4.0) Diary | 38.8 percentage of participants |
p-value: 0.572895% CI: [0.46, 1.53]Cochran-Mantel-Haenszel
Secondary
Time of Onset of a ≥35% Reduction in Spleen Volume
The time to the first ≥35% reduction in spleen volume is defined as the time from randomization to the first time participants had ≥35% reduction in spleen volume.
Time frame: up to 925 days
Population: ITT Population, including censored participants. Censored participants didn't have a response at any time up to the last assessment date. Participants who didn't have a \>=35% reduction in spleen volume were censored at the time of the last assessment. Participants with a DIPSS risk level of Low Risk Level (0 prognostic points) were excluded from the analysis. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method with log-log transformation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Time of Onset of a ≥35% Reduction in Spleen Volume | 88.0 days |
| Placebo Plus Ruxolitinib | Time of Onset of a ≥35% Reduction in Spleen Volume | 92.0 days |
p-value: 0.1085Log Rank
Secondary
Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary
Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores.
Time frame: Baseline; up to Week 24
Population: ITT Population, including censored participants. Censored participants didn't have a response at any time up to the last assessment date. Participants who didn't have a \>=50% reduction in TSS was censored at the time of the last assessment. Participants with a DIPSS risk level of Low Risk Level (0 prognostic points) were excluded from the analysis. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method with log-log transformation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parsaclisib Plus Ruxolitinib | Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary | 67.0 days |
| Placebo Plus Ruxolitinib | Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary | 69.0 days |
p-value: 0.949Log Rank