Trial Outcomes & Findings for Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2) (NCT NCT04603495)

Last Updated: 2026-07-17

Results Overview

Splenic response was characterized by a reduction of at least 35% in spleen volume from baseline (SVR35), as determined by magnetic resonance imaging (MRI) or computerized tomography (CT), and evaluated through a blinded central radiology review at Week 24.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

430 participants

Primary outcome timeframe

Week 24

Results posted on

2026-07-17

Participant Flow

A total of 135 centers enrolled patients in the study in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Malaysia, Netherlands, Poland, South Korea, Spain, Taiwan, Thailand, Turkey, United Kingdom, and United States.

Participant milestones

Participant milestones
Measure	Pelabresib + Ruxolitinib (Experimental Arm) Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Overall Study STARTED	214	216
Overall Study Modified Intent-to-Treat (mITT) Analysis Set	212	214
Overall Study Safety Analysis Set	212	214
Overall Study Per-Protocol Set (PP Set)	196	194
Overall Study Pharmacokinetic (PK) Analysis Set	212	211
Overall Study Biomarker Analysis Set	212	214
Overall Study Ongoing on Double-blind Treatment	154	160
Overall Study Discontinued Double-blind Treatment	58	54
Overall Study On PFS/OS Follow-up	22	30
Overall Study COMPLETED	176	190
Overall Study NOT COMPLETED	38	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Pelabresib + Ruxolitinib (Experimental Arm) Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Overall Study Adverse Event	2	1
Overall Study Death	10	11
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	3	3
Overall Study Patient non-compliance/protocol violation(s)	2	0
Overall Study Withdrawal of consent for follow-up	21	9
Overall Study Patient became eligible for transplant	0	1

Baseline Characteristics

Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=214 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=216 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Total n=430 Participants Total of all reporting groups
Age, Categorical Between 18 and 65 years	94 Participants n=20 Participants	92 Participants n=20 Participants	186 Participants n=40 Participants
Age, Categorical >=65 years	120 Participants n=20 Participants	124 Participants n=20 Participants	244 Participants n=40 Participants
Age, Categorical <=18 years	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Age, Continuous	64.5 years STANDARD_DEVIATION 11.84 • n=20 Participants	64.8 years STANDARD_DEVIATION 11.08 • n=20 Participants	64.7 years STANDARD_DEVIATION 11.45 • n=40 Participants
Sex: Female, Male Female	85 Participants n=20 Participants	94 Participants n=20 Participants	179 Participants n=40 Participants
Sex: Female, Male Male	129 Participants n=20 Participants	122 Participants n=20 Participants	251 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=20 Participants	6 Participants n=20 Participants	9 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	194 Participants n=20 Participants	199 Participants n=20 Participants	393 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=20 Participants	11 Participants n=20 Participants	28 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=20 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Asian	35 Participants n=20 Participants	42 Participants n=20 Participants	77 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	2 Participants n=20 Participants	0 Participants n=20 Participants	2 Participants n=40 Participants
Race (NIH/OMB) White	160 Participants n=20 Participants	163 Participants n=20 Participants	323 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	16 Participants n=20 Participants	11 Participants n=20 Participants	27 Participants n=40 Participants
Dynamic International Prognostic Scoring System (DIPSS) risk category Intermediate-1	128 Participants n=20 Participants	127 Participants n=20 Participants	255 Participants n=40 Participants
Hemoglobin ≤10 g/dL	70 Participants n=20 Participants	76 Participants n=20 Participants	146 Participants n=40 Participants
Diagnosis Primary Myelofibrosis (PMF)	107 Participants n=20 Participants	110 Participants n=20 Participants	217 Participants n=40 Participants
Dynamic International Prognostic Scoring System (DIPSS) risk category Intermediate-2	75 Participants n=20 Participants	74 Participants n=20 Participants	149 Participants n=40 Participants
Dynamic International Prognostic Scoring System (DIPSS) risk category High	11 Participants n=20 Participants	15 Participants n=20 Participants	26 Participants n=40 Participants
Platelet count >200 × 10^9 cells/L	154 Participants n=20 Participants	157 Participants n=20 Participants	311 Participants n=40 Participants
Platelet count 100-200 × 10^9 cells/L	59 Participants n=20 Participants	57 Participants n=20 Participants	116 Participants n=40 Participants
Platelet count <100 × 10^9 cells/L	1 Participants n=20 Participants	2 Participants n=20 Participants	3 Participants n=40 Participants
Hemoglobin >10 g/dL	144 Participants n=20 Participants	140 Participants n=20 Participants	284 Participants n=40 Participants
Diagnosis Post-Polycythemia Vera Myelofibrosis (PPV-MF)	45 Participants n=20 Participants	53 Participants n=20 Participants	98 Participants n=40 Participants
Diagnosis Post-Essential Thrombocythemia Myelofibrosis (PET-MF)	62 Participants n=20 Participants	53 Participants n=20 Participants	115 Participants n=40 Participants
Spleen volume from central reads	1522.43 cm^3 STANDARD_DEVIATION 950.18 • n=20 Participants	1539.28 cm^3 STANDARD_DEVIATION 920.78 • n=20 Participants	1530.90 cm^3 STANDARD_DEVIATION 934.47 • n=40 Participants
Baseline Total Symptom Score (TSS)	28.26 units on a scale STANDARD_DEVIATION 12.70 • n=20 Participants	27.36 units on a scale STANDARD_DEVIATION 12.30 • n=20 Participants	27.81 units on a scale STANDARD_DEVIATION 12.50 • n=40 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent-to-Treat (ITT) Analysis Set

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=214 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=216 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Number of Participants With Splenic Response by Central Radiology Reads at Week 24	141 Participants	76 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat (ITT) Analysis Set

The Total Symptom Score (TSS) at Week 24, compared to baseline, was measured using the Myelofibrosis Symptom Assessment Form v4.0. This score represented the sum of seven individual symptom items, each rated on a 0-10 scale, resulting in a possible total daily score ranging from 0 to 70. A higher TSS reflected a greater disease burden and therefore a worse outcome. The baseline TSS was calculated as the average of non-missing daily total symptom scores over the seven-day period preceding the day of randomization. The TSS for each treatment week was determined as the average of non-missing daily total symptom scores for that week. However, if fewer than four daily scores were available for a given week, the weekly TSS was considered missing.

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=214 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=216 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Key Secondary: Absolute Change From Baseline in Total Symptom Score (TSS) at Week 24	-15.99 score on a scale Standard Error 1.028	-14.05 score on a scale Standard Error 0.986

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-Treat (ITT) Analysis Set

The probability of a TSS response at Week 24 was estimated by calculating the TSS response rate, defined as the percentage of patients who achieved a TSS50 response at Week 24 in each of the two treatment groups. The Total Symptom Score (TSS) response was defined as a ≥50% reduction from baseline in TSS, as measured by the Myelofibrosis Symptom Assessment Form v4.0.

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=214 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=216 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Key Secondary: Number of Participants With TSS50 Response at Week 24	112 Participants	100 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat (ITT) Analysis Set

Percent Change From Baseline in Total Symptom Score (TSS) at Week 24 measured the change in a patient's symptoms after 24 weeks of treatment, relative to baseline. A negative value indicates symptom improvement, and a reduction of ≥50% is typically considered a meaningful clinical response.

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=184 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=193 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Percent Change From Baseline in Total Symptom Score (TSS) at Week 24	-50.3 Percent change from baseline to Week 24 Interval -56.6 to -44.0	-45.9 Percent change from baseline to Week 24 Interval -51.8 to -40.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat (ITT) Analysis Set: Only participants with available data at the specified time point were included in the analysis.

Improvement in bone marrow fibrosis by at least 1 grade, as assessed by central read compared to baseline, was analyzed by treatment group and overall. The improvement in bone marrow fibrosis grade was defined as a decrease by at least 1 grade in bone marrow fibrosis grade when compared to baseline, where a grade of MF-3 was the most severe, and MF-0 was the least severe.

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=192 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=188 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Number of Participants With Improvement From Baseline in Bone Marrow Fibrosis of at Least 1 Grade at Week 24	36 Participants	21 Participants

SECONDARY outcome

Timeframe: Week 48

Splenic response is characterized by a reduction of at least 35% in spleen volume from baseline (SVR35), as determined by magnetic resonance imaging (MRI) or computerized tomography (CT), and evaluated through a blinded central radiology review at Week 48.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

The probability of a TSS response at Week 48 is estimated by calculating the TSS response rate, defined as the percentage of patients who achieve a TSS50 response at Week 48 in each of the two treatment groups. The Total Symptom Score (TSS) response is defined as a ≥50% reduction from baseline in TSS, as measured by the Myelofibrosis Symptom Assessment Form v4.0.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 48

The Total Symptom Score (TSS) at Week 48, compared to baseline, is measured using the Myelofibrosis Symptom Assessment Form v4.0. This score represents the sum of seven individual symptom items, each rated on a 0-10 scale, resulting in a possible total daily score ranging from 0 to 70. A higher TSS reflects a greater disease burden and therefore a worse outcome. The baseline TSS is calculated as the average of non-missing daily total symptom scores over the seven-day period preceding the day of randomization. The TSS for each treatment week is determined as the average of non-missing daily total symptom scores for that week. However, if fewer than four daily scores are available for a given week, the weekly TSS is considered missing.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-Treat (ITT) Analysis Set

The rate of RBC transfusions was defined as the average number of RBC units transfused per patient month (4 weeks) during the first 24 weeks of treatment. The average number of RBC units per patient-month was calculated by dividing the total (ie, for all patients) number of RBC units in the whole exposure time by the sum of patient-months.

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=195 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=201 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Rate of Red Blood Cell (RBC) Transfusion Over First 24 Weeks of Treatment	1.359 RBC units transfused/patient-months Interval 0.982 to 1.736	1.014 RBC units transfused/patient-months Interval 0.84 to 1.188

SECONDARY outcome

Timeframe: From 12-week baseline period prior to dosing to any 12-week period post baseline, up to 24 weeks

Population: Intent-to-Treat (ITT) Analysis Set

Transfusion dependence (TD) was defined as having received ≥6 units of RBCs during the 12-week baseline period prior to dosing and Transfusion independence (TI) was defined as the absence of RBC transfusions during any continuous 12-week period of the double-blind treatment phase. The conversion from TD to TI was evaluated and defined as the proportion of patients who transitioned from transfusion dependence to transfusion independence. Patients who remained in the double-blind treatment period and had not received any RBC transfusions during the most recent 12 weeks were considered responders. Patients who discontinued from the double-blind treatment before Week 12 were classified as non-responders.

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=214 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=216 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Number of Participants Who Transitioned From Red Blood Cell (RBC) Transfusion Dependence to Transfusion Independence	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat (ITT) Analysis Set - Only participants with evaluable data at the pre-specified time points

The Patient Global Impression of Change (PGIC) was a single-item measure of the patient's perceived change in MF symptoms since starting treatment. Patients responded to: "Since beginning this study treatment, your myelofibrosis symptoms were: (1) Very much improved, (2) Much improved, (3) Minimally improved, (4) No change, (5) Minimally worse, (6) Much worse, (7) Very much worse."

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=177 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=194 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24 Very much worse	1 Participants	0 Participants
Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24 Very much improved	24 Participants	26 Participants
Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24 Much improved	63 Participants	62 Participants
Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24 Minimally improved	63 Participants	79 Participants
Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24 No change	14 Participants	13 Participants
Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24 Minimally worse	7 Participants	14 Participants
Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24 Much worse	5 Participants	0 Participants

SECONDARY outcome

Timeframe: Through study completion, an average of 6 years

Progression-Free Survival (PFS), defined as the time from randomization until documented progression, or until death from any cause for patients without documented progression

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through study completion, an average of 6 years

OS, defined as the time from randomization until death from any cause

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through study completion, an average of 6 years

Patients are categorized as having transformed to Acute Myelogenous Leukemia (AML) when the peripheral blood blast percentage increases to ≥20% and this elevation persists for at least two weeks, or when leukemic transformation is confirmed through disease status assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through study completion, an average of 6 years

A treatment-emergent adverse event (TEAE) for the double-blind treatment period is defined as an AE that has a start date on or after the first dose of the pelabresib/placebo and before 30 days after the last dose of pelabresib/placebo or before the start of alternative (off-study) treatment for MF, whichever occurs first. If the AE has a start date before the date of first dose but increases in severity after first dose and before 30 days post last dose will be considered a TEAE as well. An AE that occurs after the administration of the first dose of open-label pelabresib treatment will be considered treatment-emergent for the crossover treatment period. However, a TEAE for the crossover treatment period that occurs within 30 days after the last dose of pelabresib/placebo will be considered treatment emergent for the double-blind treatment period as well.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days

Pharmacokinetic (PK) parameters will be calculated based on Pelabresib plasma concentrations and actual sampling time points. AUC0-t will be listed and summarized using descriptive statistics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Pharmacokinetic (PK) parameters will be calculated based on Pelabresib plasma concentrations and actual sampling time points. AUC0-t will be listed and summarized using descriptive statistics. Tmax will be listed and summarized using descriptive statistics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Pharmacokinetic (PK) parameters will be calculated based on Pelabresib plasma concentrations and actual sampling time points. AUC0-t will be listed and summarized using descriptive statistics. Cmax will be listed and summarized using descriptive statistics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Pharmacokinetic (PK) parameters will be calculated based on Pelabresib plasma concentrations and actual sampling time points. T1/2 will be listed and summarized using descriptive statistics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Pharmacokinetic (PK) parameters will be calculated based on Pelabresib plasma concentrations and actual sampling time points. Vd/F will be listed and summarized using descriptive statistics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Pharmacokinetic (PK) parameters will be calculated based on Pelabresib plasma concentrations and actual sampling time points. CL/F will be listed and summarized using descriptive statistics.

Outcome measures

Outcome data not reported

SECONDARY outcome

Blood samples (approximately 4 mL each) will be collected at the time points specified in the Schedule of Assessments (SOA) to determine plasma concentrations of Ruxolitinib plasma concentrations in the presence or absence of Pelabresib

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through study completion, an average of 6 years

Duration of splenic response, defined as the time from onset of splenic response until the time at which the patient has a \<35% decrease from baseline in spleen volume and a \>25% increase from nadir, as confirmed by the central review) or death, whichever comes first

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-Treat (ITT) Analysis Set

The modified TSS (mTSS) was defined as TSS without the fatigue sub-domain and with a total scale of 60 points versus 70 points for TSS. Patients were classified as responders if the percentage of change from baseline in mTSS was ≤ -50% at Week 24.

Outcome measures

Outcome measures
Measure	Pelabresib + Ruxolitinib (Experimental Arm) n=214 Participants Pelabresib 125 mg orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle	Placebo + Ruxolitinib (Control Arm) n=216 Participants Matching placebo orally (PO) once daily (QD) + ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 14 consecutive days followed by ruxolitinib 10 or 15 mg orally (PO) twice a day (BID) for 7 days in a 21-day cycle
Number of Participants With Modified Total Symptom Score (mTSS) Response at Week 24	120 Participants	104 Participants

SECONDARY outcome

Timeframe: Through study completion, an average of 6 years

Duration of TSS response, defined as the time from onset of TSS50 response until the time at which the patient has a \<50% reduction in TSS from baseline and an increase of ≥25% from nadir

Outcome measures

Outcome data not reported

Adverse Events

Pelabresib + Ruxolitinib (On-Treatment)

Serious events: 63 serious events

Other events: 199 other events

Deaths: 5 deaths

Placebo + Ruxolitinib (On-Treatment)

Serious events: 63 serious events

Other events: 200 other events

Deaths: 6 deaths

Pelabresib + Ruxolitinib (Post-Treatment)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 7 deaths

Placebo + Ruxolitinib (Post-Treatment)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER