To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)

A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kδ Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib

The purpose of the study is to compare the efficacy and safety of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis who have suboptimal response while receiving ruxolitinib monotherapy.

Study Overview

• Status: Terminated
• Conditions: Primary Myelofibrosis; Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis; Post Polycythemia Vera Myelofibrosis
• Intervention / Treatment: Drug: placebo; Drug: parsaclisib; Drug: ruxolitinib

Detailed Description

Prospective participants must be on stable doses of ruxolitinib ranging from 5 mg BID to 25 mg BID and will have been on that dose for at least the last 8 weeks prior to Day 1. At least 3 months duration of prior ruxolitinib is required. Participants must meet Protocol-defined criteria for suboptimal response to ruxolitinib monotherapy. After participants have been determined to be eligible for the study and completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2 treatment groups, with stratification for platelet count (≥ 100 × 10^9/L vs 50 to < 100 × 10^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs intermediate-1).

Once a participant has completed the week 24 assessments, the participant's treatment assignment will then be unblinded and if found to be placebo, the participant will have the opportunity to crossover to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 01140
    • Hanusch-Krankenhaus Wiener Gebietskrankenkasse
• Belgium
  • Bruges, Belgium, 08000
    • A.Z. St.-Jan A.V.
  • Hasselt, Belgium, 3500
    • Jessa ziekenhuis
  • Roeselare, Belgium, 8800
    • AZ Delta
  • Yvoir, Belgium, 05530
    • Chu Ucl Namur University Hospital Mont-Godinne
• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100053
    • Xuanwu Hospital Capital Medical University
  • Beijing, China, 100091
    • Peking University Third Hospital
  • Beijing, China, 100044
    • Peking University People'S Hospital (Pkuph) - Institute of Hematology
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changzhou, China, 213003
    • The First Peoples Hospital of Changzhou
  • Fuzhou, China, 350001
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510515
    • Nanfang Hospital
  • Hangzhou, China, 310003
    • The First Affiliated Hospital of Zhejiang University
  • Harbin, China, 150010
    • Harbin Institute of Hematology and Oncology
  • Hefei, China, 230022
    • University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital)
  • Hohhot, China, 10050
    • The Affiliated Hospital of Inner Mongolia Medical University
  • Jinan, China, 250013
    • Jinan Central Hospital
  • Kunming, China, 650101
    • The Second Affiliated Hospital of Kunming Medical University
  • Lanzhou, China, 730000
    • The First Hospital of Lanzhou University
  • Lanzhou, China, 730030
    • Lanzhou University Second Hospital
  • Nanchang, China, 330006
    • The First Affiliated Hospital of Nanchang University
  • Nanchang, China, 330000
    • Jiangxi Provincial of People Hospital
  • Nanjing, China, 210029
    • Jiangsu Province Hospital
  • Qingdao, China, 266003
    • The affiliated hospital of Qingdao university
  • Shenyang, China, 110001
    • The First Hospital of China Medical University
  • Shenzhen, China, 518055
    • Shenzhen University Hospital
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Tianjin, China, 510080
    • Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Pek
  • Wuhan, China, 430030
    • Tongji Hospital Huazhong University of Science and Technology
  • Wuhan, China, 430022
    • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Xi'an, China, 710004
    • The Second Affiliated Hospital of Xi an Jiaotong University
  • Yantai, China, 264000
    • Yantai Yuhuangding Hospital
  • Zhengzhou, China, 450003
    • Henan Provincial Peoples Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hostipal
• Finland
  • Helsinki, Finland, FI-00029
    • Helsinki University Central Hospital
• France
  • La Tronche, France, 38700
    • Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes) - Hopital Albert Michallon
  • Limoges, France, 87042
    • CHU de Limoges
  • Limoges, France, 87042
    • CHU Limoges - Hopital Duputren
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
  • Nîmes, France, 30900
    • CHU Nîmes
  • Paris, France, 75012
    • Hospital Saint Antoine
  • Paris, France, 75010
    • Ap-Hp Groupe Hospitalier Saint-Louis Lariboisiere Fernand-Widal Site Saint Louis (Paris)
  • Pierre-Bénite, France, 69495
    • Hospices Civils de Lyon Centre Hospitalier Lyon Sud
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer de Toulouse Oncopole
  • Vandœuvre-lès-Nancy, France, 54500
    • Chu Vandoeuvre-Les-Nancy Hopital Brabois
• Germany
  • Bonn, Germany, 53127
    • Universitatsklinikum Bonn Aoer
  • Greifswald, Germany, 17475
    • Universitaetsmedizin Greifswald
  • Halle, Germany, 06120
    • Universitätsklinikum Halle (Saale)
  • Rostock, Germany, 18057
    • Universitaetsmedizin Rostock
• Hungary
  • Budapest, Hungary, 01088
    • Semmelweis Egyetem
  • Eger, Hungary, 03300
    • Markhot Ferenc Korhaz
  • Győr, Hungary, 09024
    • Petz Aladár County Teaching Hospital
• Israel
  • Ashdod, Israel, 7747629
    • Samson Assuta Ashdod University Hospital
  • Haifa, Israel, 31999
    • Rambam Health Care Campus
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Medical Center Ein Karem Hadassah
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Tel Aviv, Israel, 69710
    • Assuta Ramat Hahayal
• Italy
  • Avellino, Italy, 83100
    • Azienda Ospedaliera San Giuseppe Moscati
  • Bari, Italy, 70124
    • Aou Policlinico Consorziale Di Bari
  • Bologna, Italy, 40138
    • Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or
  • Catania, Italy, 11111
    • Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi
  • Florence, Italy, 50134
    • University of Florence
  • Genova, Italy, 16132
    • Irccs Azienda Ospedaliera Universitaria San Martino
  • Milan, Italy, 20122
    • Fondazione Irccs Ca Granda Ospedale Maggiore
  • Napoli, Italy, 80131
    • Università di Napoli Federico II
  • Novara, Italy, 28100
    • Azienda Ospedaliero Universitaria Maggiore della Carità di Novara
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
  • Perugia, Italy, 06156
    • Ospedale S.Maria Della Misericordia
  • Perugia, Italy, 6156
    • Ospedale S.Maria Della Misericordia
  • Pescara, Italy, 65124
    • Presidio Ospedaliero Pescara
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Reggio Calabria, Italy, 89133
    • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
  • Roma, Italy, 00161
    • Univ. Di Roma Facolta Di Armacia E Medicina
  • Roma, Italy, 144
    • Ospedale Sant. Eugenio
  • Rome, Italy, 00168
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
  • Taranto, Italy, 74123
    • Azienda Ospedaliera San Giuseppe Moscati
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Friuli Centrale Asu Fc
  • Varese, Italy, 21100
    • A.O. Universitaria Ospedale Di Circolo E Fondazione Macchi
• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Himeji-shi, Japan, 670-8540
    • Japanese Red Cross Society Himeji Hospital
  • Hirakata, Japan, 573-1191
    • Kansai Medical University Hospital
  • Isehara, Japan, 2591193
    • Tokai University Hospital
  • Izunokuni, Japan, 410-2211
    • Juntendo University Hospital
  • Kagoshima, Japan, 890-8520
    • Kagoshima University Hospital
  • Kitakyushu-shi, Japan, 807-8556
    • Hospital of the University of Occupation and Environmental Health
  • Kobe, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Kumamoto, Japan, 862-8655
    • Kumamoto Shinto General Hospital
  • Miyazaki, Japan, 889-1692
    • University of Miyazaki Hospital
  • Nagoya, Japan, 453-8511
    • Japanese Red Cross Nagoya Daini Hospital
  • Osaka, Japan, 545-8585
    • Osaka Metropolitan University Hospital
  • Saitama, Japan, 343-8555
    • Dokkyo Medical University Saitama Medical Center
  • Sapporo, Japan, 003-0006
    • Hokuyukai Sapporo Hokuyu Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Yamanashi, Japan, 409-3898
    • University of Yamanashi Hospital
  • Ōgaki, Japan, 5038502
    • Ogaki Municipal Hospital
• Norway
  • Bergen, Norway, 05021
    • Haukeland University Hospital
  • Lorenskog, Norway, 01478
    • Akershus University Hospital
• Poland
  • Katowice, Poland, 40-040
    • Pratia Hematologia Katowice
  • Katowice, Poland, 41-081
    • Pratia Hematologia Katowice
  • Krakow, Poland, 31-501
    • Samodzielny Publiczny Zoz Szpital Uniwersytecki W Krakowie
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1
  • Warsaw, Poland, 02-776
    • Institute of Hematology and Transfusion Medicine
• Romania
  • Bucharest, Romania, 30171
    • Spitalul Clinic Coltea - Clinica Hematologie
  • Târgu Gânguleşti, Romania, 540139
    • Spitalul Clinic Judetean de Urgenta Targu Mures
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Yangsan Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St. Mary?s Hospital
• Spain
  • Alicante, Spain, 03010
    • Hospital General Unviersitario de Alicante
  • Badalona, Spain, 08916
    • ICO Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital General Universitario Vall D Hebron
  • Barcelona, Spain, 08908
    • Institut Catala Doncologia Ico - Hospital Duran I Reynals Location
  • Las Palmas de Gran Canaria, Spain, 35010
    • Hospital Universitario Insular de Gran Canaria
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain, 24041
    • Hospital Universitario 12 de Octubre
  • Murcia, Spain, 30120
    • Hospital Universitario Virgen de la Arrixaca
  • Murcia, Spain, 30008
    • Hospital General Universitario Morales Meseguer
  • Salamanca, Spain, 37007
    • Hospital Clínico Universitario de Salamanca
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46017
    • Hospital Universitario Doctor Peset
  • Valencia, Spain, 46000
    • Hospital Universitari i Politecnic La Fe
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 00404
    • China Medical University Hospital
  • Tainan City, Taiwan, 00704
    • National Cheng Kung University (NCKU) Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Baskent University Adana Hospital
  • Ankara, Turkey (Türkiye), 06500
    • Gazi University Hospital Gazi University Faculty of Medicine
  • Istanbul, Turkey (Türkiye), 34214
    • Istanbul Medipol Universitesi Ibagcilar Medipol Mega Universitesi Hastanesi
  • Istanbul, Turkey (Türkiye), 34662
    • Baskent University Istanbul Hospital
  • Izmir, Turkey (Türkiye), 35040
    • Ege University Hospital
  • Samsun, Turkey (Türkiye), 55200
    • Ondokuz Mayis University Medicine Faculty
• United Kingdom
  • Aberdeen, United Kingdom, AB15 6RE
    • Grampian Health Board
  • Boston, United Kingdom, PE21 9QS
    • United Lincolnshire Hospitals
  • Gloucester, United Kingdom, GL1 3NN
    • Gloucestershire Royal Hospital
  • London, United Kingdom, NW1 2BU
    • University College London Hospitals NHS Foundation Trust
  • Middlesbrough, United Kingdom, Ts4 3Bw
    • James Cook University Hospital
• United States
  • California
    • Berkeley, California, United States, 94704
      • Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center
    • Fresno, California, United States, 93720
      • cCare
    • Los Angeles, California, United States, 90027-6005
      • California Research Institute (Cri)
    • Redlands, California, United States, 92373
      • Emad Ibrahim MD Inc
    • San Diego, California, United States, 92103
      • Scripps Clinic
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrated Cancer Care - Cicc
  • Connecticut
    • Stamford, Connecticut, United States, 06904
      • Stamford Hospital - Medical Oncology Hematology
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20057
      • Georgetown University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Augusta, Georgia, United States, 30912
      • Augusta University - Medical College of Georgia
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital Authority
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • MidAmerica Cancer Care
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • New Jersey Hematology Oncology Associates LLC
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center - Atlantic Health System
  • New York
    • Hawthorne, New York, United States, 10532
      • Westchester Medical Center Advanced Oncology
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Clyde, North Carolina, United States, 28721
      • Advent Health Hendersonville Park Ridge Hospital Hendersonville
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Oregon Health & Science University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Hillman Cancer Center
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Texas Oncology - Medical City Dallas
    • Dallas, Texas, United States, 75246-2092
      • Texas Oncology - Baylor Sammons Cancer Center
    • Dallas, Texas, United States, 75390-8565
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77025
      • Kelsey Seybold Clinic
    • Houston, Texas, United States, 77005
      • Renovatio Clinical
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of PMF, PPV-MF, or PET-MF.
• DIPSS risk category of intermediate-1, intermediate-2, or high.
• Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1
• Palpable spleen of ≥ 5 cm below the left costal margin on physical examination at the screening visit.
• Active symptoms of MF at the screening visit, as demonstrated by the presence of a TSS of ≥ 10 using the Screening Symptom Form.
• Participants with an ECOG performance status score of 0, 1, or 2.
• Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.
• Life expectancy of at least 24 weeks.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib).
• Use of experimental drug therapy for MF or any other standard drug used for MF (whether for treatment of MF or another indication) with the exception of ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.
• Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
• Recent history of inadequate bone marrow reserve.
• Inadequate liver and renal function at screening.
• Active bacterial, fungal, parasitic, or viral infection that requires therapy.
• Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.
• Known HIV infection.
• Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol.
• Active invasive malignancy over the previous 2 years.
• Splenic irradiation within 6 months before receiving the first dose of study drug.
• Concurrent use of any prohibited medications.
• Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements.
• Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
• Currently breastfeeding or pregnant.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• History of Grade 3 or 4 irAEs from prior immunotherapy.
• Receipt of any live vaccine within 30 days of the first dose of study drug
• Unwillingness to receive RBC transfusions to treat low hemoglobin levels.
• Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or excipients of parsaclisib/matching placebo or ruxolitinib formulations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A : ruxolitinib +parsaclisib; Participants will receive parsaclisib starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.	Drug: parsaclisib; parsaclisib will be administered QD orally; Other Names: INCB050465; Drug: ruxolitinib; ruxolitinib will be administered BID orally; Other Names: Jakafi; Jakavi
Placebo Comparator: Group B : ruxolitinib + placebo; Participants will receive placebo starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.	Drug: placebo; placebo will be administered QD orally; Drug: ruxolitinib; ruxolitinib will be administered BID orally; Other Names: Jakafi; Jakavi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving ≥25% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)	Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available.	Baseline; Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Have a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v.4.0 (MFSAF v4.0) Diary	Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as 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 score was marked as missing if there were ≥4 out of the 7 daily TSSs missing.	Baseline; Week 24
Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary	Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as 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 score was marked as missing if there were ≥4 out of the 7 daily TSSs missing. Change from Baseline was calculated as the Week 24 value minus the Baseline value.	Baseline; Week 24
Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary	Symptoms 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 in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as 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 marked as missing if there were ≥4 out of the 7 daily TSSs missing. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method with log-log transformation.	Baseline; up to Week 24
Overall Survival	Overall survival was defined as the interval between the randomization date and the date of death due to any cause.	up to 917 days
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.	up to 917 days
Number of Participants With Any Grade 3 or Higher TEAE	An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. A TEAE is defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. 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.	up to 917 days
Time to the First ≥25% Reduction in Spleen Volume	The time to the first ≥25% reduction in spleen volume is defined as the time from randomization to the first time participants had ≥25% reduction in spleen volume. Participants with a Baseline and post-Baseline MRI or CT scan who did not have ≥25% reduction in spleen volume at the time of analysis were censored at the time of the last MRI or CT scan. If the participants had no Baseline or post-Baseline MRI or CT scan, they were censored at the date of randomization.	up to 898 days
Duration of Maintenance of a ≥25% Reduction in Spleen Volume	The duration of ≥25% reduction from Baseline in spleen volume was defined as the interval between the first spleen volume measurement that was a ≥25% reduction from Baseline and the date of the first measurement that was no longer a ≥25% reduction from Baseline. If the end date was not observed before the database cutoff, the duration was censored at the last assessment.	up to 898 days

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Albert Assad, M.D., Incyte Corporation

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2021
• Primary Completion (Actual): August 16, 2023
• Study Completion (Actual): August 21, 2024

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: MPN; Myelofibrosis; Myeloproliferative Neoplasm; MF; ruxolitinib; LIMBER; INCB050465; parsaclisib; Myoproliferative Neoplasms; LIMBER-304
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis; ruxolitinib; parsaclisib
• Other Study ID Numbers: INCB 50465-304/LIMBER-304; 2020-003415-98 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No