Trial Outcomes & Findings for To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313) (NCT NCT04551066)

Last Updated: 2025-10-21

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

252 participants

Primary outcome timeframe

Baseline; Week 24

Results posted on

2025-10-21

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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).	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.
Overall Study STARTED	125	127
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	125	127

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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.
Overall Study Death	5	3
Overall Study Lost to Follow-up	1	0
Overall Study Sponsor Decision	104	117
Overall Study Withdrawal by Subject	8	2
Overall Study Awaiting Rollover to Another Study to Receive Ruxolitinib	2	3
Overall Study Adverse Event	2	0
Overall Study Physician Decision	2	0
Overall Study Protocol Violation	1	0
Overall Study Lack of Efficacy	0	1
Overall Study Concomitant Diagnosis of Mature Plasmacytoid Dendritic Cell Proliferation	0	1

Baseline Characteristics

To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parsaclisib Plus Ruxolitinib n=125 Participants 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).	Placebo Plus Ruxolitinib n=127 Participants 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.	Total n=252 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 10.34 • n=5 Participants	63.3 years STANDARD_DEVIATION 10.90 • n=7 Participants	63.3 years STANDARD_DEVIATION 10.61 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	49 Participants n=7 Participants	98 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	78 Participants n=7 Participants	154 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	103 Participants n=5 Participants	110 Participants n=7 Participants	213 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	10 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	80 Participants n=5 Participants	84 Participants n=7 Participants	164 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	33 Participants n=5 Participants	31 Participants n=7 Participants	64 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Captured as "Not Hispanic, Latino or Spanish" in Database	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Turkish	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=89 Participants 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).	Placebo Plus Ruxolitinib n=92 Participants 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.
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	46.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=89 Participants 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).	Placebo Plus Ruxolitinib n=98 Participants 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.
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	38.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: ITT Population. Only participants with available data were analyzed.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=119 Participants 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).	Placebo Plus Ruxolitinib n=125 Participants 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.
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	19.6 scores on a scale Standard Deviation 13.07
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	-6.8 scores on a scale Standard Deviation 10.74

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=125 Participants 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).	Placebo Plus Ruxolitinib n=127 Participants 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.
Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary	67.0 days Interval 27.0 to 131.0	69.0 days Interval 35.0 to 143.0

SECONDARY outcome

Timeframe: up to 749 days

Population: ITT Population

Overall survival was defined as the interval between the randomization date and the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=125 Participants 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).	Placebo Plus Ruxolitinib n=127 Participants 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.
Overall Survival	NA days Due to participants rolling over to another study (NCT02955940), the follow-up time was not long enough to estimate the median and the upper and lower limits of the confidence interval.	NA days Due to participants rolling over to another study (NCT02955940), the follow-up time was not long enough to estimate the median and the upper and lower limits of the confidence interval.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=125 Participants 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).	Placebo Plus Ruxolitinib n=127 Participants 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.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	117 Participants	119 Participants

SECONDARY outcome

Timeframe: up to 960 days

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=125 Participants 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).	Placebo Plus Ruxolitinib n=127 Participants 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.
Number of Participants With Any Grade 3 or Higher TEAE	75 Participants	75 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=125 Participants 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).	Placebo Plus Ruxolitinib n=127 Participants 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.
Time of Onset of a ≥35% Reduction in Spleen Volume	88.0 days Interval 86.0 to 99.0	92.0 days Interval 87.0 to 253.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Parsaclisib Plus Ruxolitinib n=73 Participants 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).	Placebo Plus Ruxolitinib n=61 Participants 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.
Duration of Maintenance of a ≥35% Reduction in Spleen Volume	505.0 days Interval 339.0 to The upper limit of the confidence interval was not estimable because too few participants lost a \>=35% reduction in spleen volume at the time of rollover to another study (NCT02955940).	NA days Interval 337.0 to The median and the upper limit of the confidence interval were not estimable because too few participants lost a \>=35% reduction in spleen volume at the time of rollover to another study (NCT02955940).

Adverse Events

Parsaclisib Plus Ruxolitinib

Serious events: 26 serious events

Other events: 109 other events

Deaths: 6 deaths

Placebo Plus Ruxolitinib

Serious events: 18 serious events

Other events: 109 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Incyte Corporation

Phone: 1-855-463-3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Publication restrictions are in place

Restriction type: OTHER