Blood and Lymph Conditions

All Conditions

Neoplasms

Rare Diseases

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

All Drugs and Chemicals

Janus Kinase Inhibitors

Participants received ruxolitinib orally twice a day. The starting dose was determined based on Baseline platelet count. Patients with Baseline platelet count \> 200,000/μL began a dose regimen of 20 mg twice daily. Patients with Baseline platelet count of 100,000/μL to 200,000/μL (inclusive) began a dose regimen of 15 mg twice daily. The dose was adjusted by the Investigator based on efficacy and safety to a maximum of 25 mg twice daily. Patients receiving benefit could continue treatment until the later of marketing approval or when the last randomized patient remaining in the study had completed Week 144 (36 months).

Placebo tablets matching ruxolitinib were administered orally twice a day at a starting dose based on Baseline platelet count. Doses were titrated using the same guidelines as for active drug. Patients meeting certain protocol requirements detailed below were given the opportunity to cross over to ruxolitinib treatment.

Ruxolitinib phosphate tablets 5 mg administered as oral doses.

Ruxolitinib

Matching placebo tablets were administered as oral doses in the same manner as active drug.

Placebo

Srdan Verstovsek, MD, PhD

This was a randomized, double-blind study comparing the efficacy and safety of ruxolitinib (INCB018424) tablets to matching placebo tablets in patients diagnosed with Myelofibrosis (either Primary Myelofibrosis (PMF) or Post-Polycythemia Vera Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia Myelofibrosis (PET-MF).

Patients with spleen growth of greater than 25% based on an increase in spleen volume from Baseline were eligible for early unblinding, and for patients on placebo, cross over to ruxolitinib prior to the primary study endpoint being reached. If this spleen growth occurred before Week 24, it must have been accompanied by specific worsening of symptoms, based on worsening early satiety accompanied by weight loss or worsening pain requiring daily narcotic use. After Week 24, asymptomatic spleen growth alone was sufficient for early unblinding and potential cross over. Patients found to have been randomized to ruxolitinib after early unblinding prior to Week 24 were discontinued.

When half of the patients remaining in the study completed the Week 36 visit and all patients enrolled completed Week 24 or discontinued, the database was frozen and the primary analysis was conducted. Once this was complete, all patients were unblinded and patients who had been randomized to placebo were given the opportunity to cross over to ruxolitinib treatment, provided hematology laboratory parameters were adequate; Patients receiving benefit could continue treatment until the later of marketing approval or when the last randomized patient remaining in the study had completed Week 144 (36 months).

COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial

A Randomized, Double-blind, Placebo-controlled Study of the JAK Inhibitor INCB018424 Tablets Administered Orally to Subjects With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis

Spleen volume was assessed by magnetic resonance imaging (MRI) or by computed tomography (CT) scans if MRI was not suitable, and analyzed by a blinded central laboratory reader. Patients who withdrew, crossed over to ruxolitinib prior to the visit, or had a missing value at the visit were considered non-responders.

The maintenance of ≥ 35% reduction from Baseline in spleen volume was assessed up until the data cutoff date using the Kaplan-Meier method for patients who had at least one measured ≥ 35% reduction, and who either had at least one subsequent measurement or who subsequently dropped out prior to another assessment.

The duration of ≥ 35% reduction from Baseline in spleen volume was defined as the longest duration of consecutive measurements of ≥ 35% reduction observed before the data cut-off date for patients who had at least one measured ≥ 35% reduction, and who either had at least one subsequent measurement or, who subsequently dropped out prior to another assessment. The duration of a ≥ 35% reduction from Baseline in spleen volume was analyzed using the Kaplan-Meier method.

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.

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 hence a negative change from baseline indicates improvement.

Overall survival is reported here by the number of deaths from randomization until the data cut-off. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method.

Overall survival was assessed by the time to death or censoring. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method.

Overall survival is reported here by the number of deaths from randomization until 01 March 2011. Patients were censored at this time or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. This outcome reports data from August 2009 through March 2011 to coincide with a pre-planned New Drug Application (NDA) 120-day safety update.

Overall survival was assessed by the time to death or censoring up until 01 March 2011. Patients were censored at this time or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. This outcome reports data from August 2009 through March 2011 to coincide with a pre-planned New Drug Application (NDA) 120-day safety update.

Overall survival is reported here by the number of deaths from randomization until the data cut-off. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of database cut-off. The survival time was analyzed using the Kaplan-Meier method.

Overall survival was assessed by the time to death or censoring. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of database cut-off. The survival time was analyzed using the Kaplan-Meier method.

Incyte Corporation

Participants began treatment with ruxolitinib 15 or 20 mg taken orally twice a day based on Baseline platelet count. The dose was adjusted by the Investigator based on efficacy and safety to a maximum of 25 mg twice daily.

Placebo tablets matching ruxolitinib were administered orally twice a day at a starting dose based on Baseline platelet count. Doses were titrated using the same guidelines as for active drug. Patients meeting pre-specified requirements were given the opportunity to cross over to ruxolitinib treatment.

Total

Age, Continuous

Female

Male

Gender data for one patient in the placebo arm was not available because of loss of study data during a move to a new location by the clinical site.

Sex/Gender, Customized

Black or African American

White

Asian

Native Hawaiian or Other Pacific Islander

Other

Race data for one patient in the placebo arm was not available because of loss of study data during a move to a new location by the clinical site.

Race/Ethnicity, Customized

Primary myelofibrosis

Post-polycythemia vera-myelofibrosis

Post-essential thrombocythemia-myelofibrosis

Missing

Disease Subtype

Spleen volume was measured by magnetic resonance imaging or computed tomography scans. Data for one patient in the placebo arm was not available because of loss of study data during a move by the clinical site.

Spleen volume

Positive

Negative

Unknown/Missing

JAK2V617F is a mutation in the pseudokinase domain of Janus Kinase 2 (JAK2) (at amino acid 617, valine to phenylalanine) that results in constitutive activation of JAK2. Mutation status was determined using a validated assay on bone marrow as well as peripheral blood.

JAK2 V617F Mutation Status

Study Director

The primary endpoint analyzed with a 2-sided alpha of 0.05.

Intent-to-treat (ITT) population included all subjects randomized in the study. Treatment groups for this population were defined according to the treatment assignment at randomization. One patient was not included in the analysis due to a missing baseline spleen volume value.

Number of Participants Achieving ≥ 35% Reduction in Spleen Volume From Baseline to Week 24

Still Responder by 48 weeks

Still Responder by 96 weeks

Still Responder by 144 weeks

Patients who had at least 1 measurement of ≥ 35% reduction from Baseline in spleen volume at any time during the study and had at least 1 subsequent measurement or withdrew prior to another assessment.

Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib

Duration of Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib

ITT evaluable population included patients with Baseline data and who did not have a 0 total score at both Baseline \& Week 24; data measured after the cross over date were excluded. Patients who withdrew, met cross over criteria prior to Week 24 or had a 0 Baseline score \& a nonzero/missing score at Week 24 were considered not meeting the endpoint.

Number of Participants With a ≥ 50% Reduction in Total Symptom Score From Baseline to Week 24

Baseline

Week 24

Change from Baseline

This analysis only includes patients who had a non-missing change from Baseline to Week 24. Data collected after the date of treatment cross over were not included in this analysis.

Change From Baseline to Week 24 in Total Symptom Score

Death events

Censored events

Overall Survival

Overall Survival Time

Overall Survival - Extended Data

Overall Survival Time - Extended Data

Overall Survival at Week 144

Overall Survival Time at Week 144

Participants received ruxolitinib orally twice a day. The starting dose was based on Baseline platelet count. Patients with Baseline platelet count \> 200,000/μL began a dose regimen of 20 mg twice daily. Patients with Baseline platelet count of 100,000/μL to 200,000/μL (inclusive) began a dose regimen of 15 mg twice daily. The dose was adjusted by the Investigator based on efficacy and safety to a maximum of 25 mg twice daily. Patients receiving benefit could continue treatment until the later of marketing approval or when the last randomized patient remaining in the study had completed Week 144 (36 months).

All Participants

Patients Who Crossed Over to Ruxolitinib

Initial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria.

Part 2 will compare 2 doses of parsaclisib .

Part 3 will compare 2 different long term dosing strategies.

Part 4 will compare 2 different daily dosing strategies.

Up to 3 oral once a day (QD) doses of parsaclisib. Doses will be taken once daily for 8 weeks, followed by once weekly dosing at the same dose level.

Parsaclisib

Two recommended oral QD doses of parsaclisib. Once daily doses of parsaclisib will be taken for 8 weeks, followed by once weekly dosing at the same dose level.

The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.

20 mg oral QD dose of parsaclisib for 8 weeks. After 8 weeks patients will take either 20 mg once weekly or 5 mg once daily.

2 dose strategies will be compared:

1. 5 mg parsaclisib beginning on Day 1 until end of treatment.
2. 20 mg oral QD dose of parsaclisib for 8 weeks; after 8 weeks patients will take 5 mg once daily.

Albert Assad, MD

The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.

A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

DLTs were defined as the occurrence of any protocol-defined toxicities occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression, other medications) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 12 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 12 visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 12 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 12 visit. Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 24 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 24 visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 24 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 24 visit. Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.

The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.

The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.

The PGIC questionnaire consists of a single question with 7 possible answers: "Since the start of 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 participant was considered as a responder if the participant had a best overall response of CR or PR. CR: (a) bone marrow (BM): age-adjusted normocellularity (AAN); \< 5% blasts; ≤ grade 1 myelofibrosis (MF); (b) peripheral blood (PD): hemoglobin (Hg) ≥ 100 grams per Liter (g/L) and \< upper normal limit (UNL); neutrophils ≥ 1 × 10\^9/L and \< UNL; (c) platelets ≥ 100 × 10\^9/L and \< UNL; \< 2% immature myeloid cells (IMCs); (d) clinical: resolution of disease symptoms; spleen/liver not palpable; no extramedullary hematopoiesis (EMH). PR: (a) PB: Hg ≥ 100 g/L and \< UNL; neutrophils ≥ 1 × 10\^9/L and \< UNL; platelets ≥ 100 × 10\^9/L and \< UNL; \< 2% IMCs; (b) clinical: resolution of disease symptoms; spleen/liver not palpable; no EMH; (c) BM: AAN; \< 5% blasts; ≤ Grade 1 MF; and PB: Hg ≥ 85 g/L but \< 100 g/L and \< UNL; neutrophils ≥ 1 × 10\^9/L and \< UNL; platelets ≥ 50 × 10\^9/L but \< 100 × 10\^9/L and \< UNL; \< 2% IMCs.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or requird changes in the study drug(s). TEAEs were defined as AEs that began or worsened from Baseline after the first administration of study drug.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or requird changes in the study drug(s). TEAEs were defined as AEs that began or worsened from Baseline after the first administration of study drug. Participants who had been assigned to dosing arms with weekly dosing beyond Week 8 had the opportunity to transition to all daily dosing at 5 mg if agreed upon by the participant and the Investigator.

Cmax was defined as the maximum observed plasma concentration.

tmax was defined as the time to the maximum concentration.

Cmin was defined as the minimum observed plasma concentration.

AUC0-4h was defined as the area under the plasma concentration-time curve from time = 0 to 4 hours post-dose.

AUC0-t was defined as the area under the plasma concentration-time curve from time =0 to the last measurable concentration at time = t.

Clast was defined as the last quantifiable concentration.

tlast was defined as the time of the last quantifiable concentration.

An AE was reported in the initial randomization group (TG10, TG20) if it started before transition to TG5D. An AE was reported in the TG5D Transition arm if it started after transition to TG5D. Due to early termination of the study, per the Statistical Analysis Plan, the 4 dosage groups (TG10: Daily/Weekly Dosing; TG20: Daily/Weekly Dosing; TG5I/M; TG5D), as well as the participants who transitioned from daily/weekly to all-daily dosing (TG5D Transition), were compared separately for safety.

Participants received at least 6 months of prior ruxolitinib therapy, including ruxolitinib administration at a stable dose of 5 mg BID to 25 mg BID for at least 8 weeks before randomization. From Day 1 to the end of Week 8, participants received oral parsaclisib 10 milligrams (mg) once daily (QD), followed by the same dose weekly until discontinuation criteria were met, in combination with the pre-Day 1 stable dose of ruxolitinib (5 to 25 mg BID).

TG10: Daily/Weekly Dosing

Participants received at least 6 months of prior ruxolitinib therapy, including ruxolitinib administration at a stable dose of 5 mg BID to 25 mg BID for at least 8 weeks before randomization. From Day 1 to the end of Week 8, participants received oral parsaclisib 20 mg QD, followed by the same dose weekly until discontinuation criteria were met, in combination with the pre-Day 1 stable dose of ruxolitinib (5 to 25 mg BID).

TG20: Daily/Weekly Dosing

Participants received at least 6 months of prior ruxolitinib therapy, including ruxolitinib administration at a stable dose of 5 milligrams (mg) twice a day (BID) to 25 mg BID for at least 8 weeks before randomization. From Day 1 to the end of Week 8, participants received oral parsaclisib 20 mg once daily (QD), followed by 5 mg QD until discontinuation criteria were met, in combination with the pre-Day 1 stable dose of ruxolitinib (5 to 25 mg BID).

TG5I/M

Participants received at least 6 months of prior ruxolitinib therapy, including ruxolitinib administration at a stable dose of 5 mg BID to 25 mg BID for at least 8 weeks before randomization. From Day 1, participants received oral parsaclisib 5 mg QD until discontinuation criteria were met, in combination with the pre-Day 1 stable dose of ruxolitinib (5 to 25 mg BID).

TG5D

Total: Initially Randomized Participants

Participants received at least 6 months of prior ruxolitinib therapy, including ruxolitinib administration at a stable dose of 5 mg BID to 25 mg BID for at least 8 weeks before randomization. Participants randomized to receive oral parsaclisib 10 mg or 20 mg QD from Day 1 to the end of Week 8 transitioned to oral parsaclisib 5 mg QD after Week 8. Transition participants received oral parsaclisib 5 mg QD until discontinuation criteria were met, in combination with the pre-Day 1 stable dose of ruxolitinib (5 to 25 mg BID).

TG5D Transition

Participants received at least 6 months of prior ruxolitinib therapy, including ruxolitinib administration at a stable dose of 5 mg BID to 25 mg BID for at least 8 weeks before randomization. From Day 1 to the end of Week 8, participants in TG10 and TG20 received oral parsaclisib 10 mg or 20 mg QD, respectively, followed by the same dose weekly until discontinuation criteria were met, in combination with the pre-Day 1 stable dose of ruxolitinib (5 to 25 mg BID).

TG10 + TG20: Daily/Weekly Dosing

Sex: Female, Male

Ethnicity (NIH/OMB)

Captured as "Other" in Database

Due to early termination of the study, per the Statistical Analysis Plan, participants were combined into arms based on the dosage received regardless of what phase of the study they participated in.

Initial Safety Population: all participants who received at least 1 dose of study drug. Treatment groups were determined according to the actual treatment the participant received regardless of assigned study drug treatment. Analysis was conducted on the Safety Population during the initial safety period. Due to early termination of the study, per the Statistical Analysis Plan, daily and weekly dosing arms were combined for analysis.

Number of Participants With Dose-limiting Toxicities (DLTs)

Change from Baseline at Week 12

Initial Safety Population: all enrolled participants who received at least 1 dose of study drug. Analysis was conducted on the Safety Population during the initial safety period. Only participants with available data were analyzed. Due to early termination of the study, per the Statistical Analysis Plan, daily and weekly dosing arms were combined for efficacy analysis.

Change From Baseline in Spleen Volume Through Week 12 of the Initial Study Period as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)

Initial Safety Population. Analysis was conducted on the Safety Population during the initial safety period. Only participants with available data were analyzed. Due to early termination of the study, per the Statistical Analysis Plan, daily and weekly dosing arms were combined for efficacy analysis.

Percent Change From Baseline in Spleen Volume Through Week 12 as Measured by MRI (or CT Scan in Applicable Participants)

Change from Baseline at Week 24

Change From Baseline in Spleen Volume Through Week 24 of the Initial Study Period as Measured by MRI (or CT Scan in Applicable Participants)

Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants )

Change From Baseline in the Total Symptom Score (TSS) Through Week 12 as Measured by Myelofibrosis Symptom Assessment Form (MFSAF) Version 3.0 (v3.0) Symptom Diary

Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary

Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary

Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary

Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)

Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF

Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF

Percent Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF

Week 12, very much improved

Week 12, much improved

Week 12, minimally improved

Week 12, no change

Week 12, minimally worse

Week 12, much worse

Week 12, very much worse

Week 12, not reported

Week 24, very much improved

Week 24, much improved

Week 24, minimally improved

Week 24, no change

Week 24, minimally worse

Week 24, much worse

Week 24, very much worse

Week 24, not reported

EOT, very much improved

EOT, much improved

EOT, minimally improved

EOT, no change

EOT, minimally worse

EOT, much worse

EOT, very much worse

EOT, not reported

Initial Safety Population. Analysis was conducted on the Safety Population during the initial safety period. Due to early termination of the study, per the Statistical Analysis Plan, daily and weekly dosing arms were combined for efficacy analysis.

Number of Participants With the Indicated Patient Global Impression of Change (PGIC) Score at Week 12, Week 24, and the End of Treatment (EOT)

Week 12

Mean PGIC Score at Week 12, Week 24, and the EOT

Best Overall Response (Percentage of Participants With Complete Response [CR] or Partial Response [PR]) for Investigator-Reported International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Response Assessment

Initial Safety Population. Analysis was conducted on the Safety Population during the initial safety period. Due to early termination of the study, per the Statistical Analysis Plan, daily and weekly dosing arms were combined for analysis.

Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

Transition Safety Population. AEs were reported in the initial randomization group (TG10, TG20) if the start of the AEs occurred before transitioning to TG5D. If the start of the AEs occurred after transitioning to TG5D, they were reported in the TG5D Transition arm.

Number of Participants With Any TEAE During the Transition Period

Week 2

Week 4

Pharmacokinetic (PK) Population: all treated participants who contributed plasma PK samples. Only participants with available data were analyzed. To be able to form a meaningful statistical test with enough participants, participants across all treatment groups were combined according to the dose of parsaclisib received for analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial	NCT00952289	MPN (Myeloproli...	Ruxolitinib Placebo	18 Years -	Incyte Corporation
A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis	NCT02718300	MPN (Myeloproli...	Parsaclisib Parsaclisib Ruxolitinib Parsaclisib Parsaclisib	18 Years -	Incyte Corporation
An Open Label Study of Itacitinib Administered Orally in Patients With Myelofibrosis	NCT01633372	MPN (Myeloproli...	itacitinib	18 Years -	Incyte Corporation
Prospective Observational Study Of Patients With Polycythemia Vera In US Clinical Practices (REVEAL)	NCT02252159	MPN (Myeloproli...		18 Years -	Incyte Corporation
Myelofibrosis and Essential Thrombocythemia Observational Study (MOST)	NCT02953704	MPN (Myeloproli...		18 Years -	Incyte Corporation
Myelofibrosis and Essential Thrombocythemia Observational Study (MOST)	NCT02953704	MPN (Myeloproli...		18 Years -	Incyte Corporation
An Open Label Study of Itacitinib Administered Orally in Patients With Myelofibrosis	NCT01633372	MPN (Myeloproli...	itacitinib	18 Years -	Incyte Corporation
Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)	NCT03123588	MPN (Myeloproli...	Ruxolitinib Anagrelide Placebo Placebo	18 Years -	Incyte Corporation
An Open Label Study of Itacitinib Administered Orally in Patients With Myelofibrosis	NCT01633372	MPN (Myeloproli...	itacitinib	18 Years -	Incyte Corporation
COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial	NCT00952289	MPN (Myeloproli...	Ruxolitinib Placebo	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for mpn (myeloproliferative neoplasms)