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

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Combination of PI3Kδ Inhibitor Parsaclisib and Ruxolitinib in Participants With Myelofibrosis

The purpose of the study is to compare the efficacy of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis.

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

This is a Phase 3, randomized, double-blind study of the combination of the PI3Kδ inhibitor parsaclisib or matching placebo and the JAK1/2 inhibitor ruxolitinib in participants with PMF or secondary MF (PPV-MF or PET-MF) with DIPSS risk category of intermediate or high. Prospective participants must have not received prior MF therapy with a JAK inhibitor or a PI3K inhibitor. After participants have been determined to be eligible for the study and completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2 treatment groups, with stratification for platelet count (≥ 100 × 10^9/L vs 50 to < 100 × 10^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs intermediate-1).

Once all enrolled participants completed the week 24 assessments the study will be unblinded and and participants randomized to placebo will have the opportunity to cross over to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 04020
    • Ordensklinikum Linz GmbH Elisabethinen
  • Saint P�LTEN, Austria, 03100
    • Universitaetsklinikum St. Poelten
  • Vienna, Austria, 01140
    • Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse
  • Vienna, Austria, 01140
    • Hanusch-Krankenhaus Wiener Gebietskrankenkasse
• Belgium
  • Bruges, Belgium, 08000
    • A.Z. St.-Jan A.V.
  • Brussels, Belgium, 01000
    • Cliniques Universitaires Ucl Saint-Luc
  • Charleroi, Belgium, 06000
    • Grand hospital de Charleroi
  • Hasselt, Belgium, 03500
    • Jessa Ziekenhuis
  • Roeselare, Belgium, 08800
    • AZ Delta
• China
  • Baoding, China, 71000
    • Affiliated Hospital of Hebei 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
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Fuzhou, China, 350001
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510515
    • Nanfang Hospital
  • Guangzhou, China, 510080
    • Guangdong Provincial of People Hospital
  • Hangzhou, China, 310003
    • The First Affiliated Hospital of Zhejiang University
  • Harbin, China, 150010
    • Harbin Institute of Hematology and Oncology
  • Hefei, China, 230001
    • Anhui Provincial Hospital
  • Hohhot, China, 10050
    • The Affiliated Hospital of Inner Mongolia Medical University
  • Jinan, China, 250013
    • Jinan Central Hospital
  • 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
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Shenzhen, China, 518055
    • Shenzhen University Hospital
  • Shijiazhuang, China, 50000
    • The Second Hospital of Hebei Medical University
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Wenzhou, China, 325000
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan, China, 430022
    • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Yantai, China, 264000
    • Yantai Yuhuangding Hospital
  • Zhengzhou, China, 450003
    • Henan Provincial Peoples Hospital
• Denmark
  • Aalborg, Denmark, 09000
    • Aalborg University Hospital
  • Odense, Denmark, 05000
    • Odense University Hospital
• Finland
  • Helsinki, Finland, FI-00029
    • Helsinki University Central Hospital
• France
  • LE Chesnay-rocquencourt, France, 78157
    • Centre Hospitalier de Versailles - Hopital Andre Mignot
  • La Tronche, France, 38700
    • Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes) - Hopital Albert Michallon
  • Limoges, France, 87042
    • CHU Limoges - Hopital Dupuytren
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu
  • Nîmes, France, 30900
    • Chu Nimes
  • 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
  • Poitiers, France, 86021
    • Hospital de La Miletrie
  • Rennes, France, 35033
    • Chu de Rennes - Hospital Pontchaillou
  • Roubaix, France, 59100
    • Centre Hospitalier de Roubaix
• Germany
  • Halle, Germany, 06120
    • Universitatsklinikum Halle (Saale)
  • Kassel, Germany, 34125
    • Klinikum Kassel GmbH
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg A.ö.R.
  • Rostock, Germany, 18057
    • Universitaetsmedizin Rostock
• Israel
  • BEER Yaaqov, Israel, 70300
    • Shamir Medical Center Formerly Assaf Harofeh Medical Center
  • Haifa, Israel, 31999
    • Rambam Health Care Campus
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Medical Center Ein Karem Hadassah
  • Petah Tikva, Israel, 49100
    • Davidoff Cancer Center Rabin Medical Center
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Tel Aviv, Israel, 69710
    • Assuta Ramat Hahayal
• Italy
  • Bologna, Italy, 40138
    • Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or
  • Catania, Italy, 95123
    • Azienda Policlinico Vittorio Emanuele
  • Genova, Italy, 16132
    • Universita Degli Studi Di Genova - Facolta Di Medicina E Chirurgia
  • Meldola, Italy, 47014
    • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
  • Milan, Italy, 20132
    • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
  • Milan, Italy, 20122
    • Fondazione Irccs Ca Granda Ospedale Maggiore
  • Napoli, Italy, 80131
    • Universita Di Napoli Federico Ii
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
  • Pesaro, Italy, 61122
    • Aormn Hospital Hematology and Bmt Center
  • Reggio Calabria, Italy, 89133
    • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
  • Roma, Italy, 00133
    • Universita Di Roma Tor Vergata
  • Roma, Italy, 00161
    • Universita Di Roma
  • Rome, Italy, 00168
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
  • Salerno, Italy, 84131
    • AOU San Giovanni di Dio e Ruggi d'Aragona
  • 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
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba cancer center
  • Chūō, Japan, 409-3898
    • University of Yamanashi Hospital
  • 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
  • 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
  • Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tsu, Japan, 514-0001
    • Mie University Hospital
  • Yokohama, Japan, 221-0855
    • Yokohama Municipal Citizens Hospital
  • Ōgaki, Japan, 5038502
    • Ogaki Municipal Hospital
• Norway
  • Bergen, Norway, 05021
    • Haukeland University Hospital
  • L�RENSKOG, Norway, 01478
    • Akershus University Hospital
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Katowice, Poland, 40-027
    • Samodzielny Publiczny Szpital Kliniczny Im. Andrzeja Mielckiego
  • Katowice, Poland, 41-519
    • Pratia Hematologia Katowice
  • Krakow, Poland, 31-501
    • Sp Zoz Szpital Uniwersytecki
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1
  • Warsaw, Poland, 02-776
    • Institute of Hematology and Transfusion Medicine
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 03651
    • Samsung Medical Center
  • Seoul, South Korea, 06591
    • THE CATHOLIC UNIVERSITY OF KOREA SEOUL ST. MARY�S HOSPITAL
  • Wŏnju, South Korea, 26426
    • WonJu Severance Christian Hospital
• Spain
  • Alicante, Spain, 3010
    • 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
    • ICO-Hospital Duran i Reynals
  • Barcelona, Spain, 08908
    • Institut Catala Doncologia Ico - Hospital Duran I Reynals Location
  • Barcelona, Spain, 08916
    • ICO Hospital Germans Trias i Pujol
  • Bilbao, Spain, 48013
    • Hospital de Basurto
  • El Palmar, Spain, 30120
    • Hospital Universitario Virgen de la Arrixaca
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Las Palmas de Gran Canaria, Spain, 35010
    • Hospital Universitario Insular de Gran Canaria
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Fundacian Jimnez Diaz
  • Murcia, Spain, 30008
    • Hospital General Universitario Morales Meseguer
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Valencia, Spain, 46017
    • Hospital Universitario Doctor Peset
  • Valencia, Spain, 46000
    • Hospital Universitari i Politecnic La Fe
• 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
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylül University
  • Samsun, Turkey (Türkiye), 55200
    • Ondokuz Mayis University Medicine Faculty
• United Kingdom
  • 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
  • London, United Kingdom, EC1A 7BE
    • Barts Health Nhs Trust - St Bartholomews Hospital
  • Sheffield, United Kingdom, S5 7AT
    • Sheffield Teaching Hospitals Nhs Foundation Trust - Weston Park Hospital
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • University Hospital of North Midlands NHS Trust
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Rochester
  • 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, 90095-3075
      • UCLA School of Medicine
    • Los Angeles, California, United States, 90027-6005
      • California Research Institute (Cri)
    • 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
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital Authority
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky-Markey Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • 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
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Hawthorne, New York, United States, 10532
      • Westchester Medical Center Advanced Oncology and Infusion Center
    • 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
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente-Northwest
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57103
      • Avera Cancer Institute
  • Texas
    • Dallas, Texas, United States, 75246-2092
      • Texas Oncology-Baylor Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77025
      • Kelsey Seybold Clinic
    • Spring, Texas, United States, 77380
      • Renovatio Clinical
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

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

Exclusion Criteria:

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

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 : parsaclisib + ruxolitinib; Participants will receive parsaclisib and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.	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 : placebo + ruxolitinib; Participants will receive placebo and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.	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 ≥35% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging [MRI] (or Computed Tomography [CT] Scan in Applicable Participants)	Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available. Determination of spleen length below the left costal margin was measured by palpation, using a flexible ruler provided by the sponsor.	Baseline; Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Had a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v4.0 (MFSAF v4.0) Diary	Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores.	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 on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.	Baseline; Week 24
Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary	Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected on the same day. Higher TSS indicate more severe symptoms. The TSS was missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was missing if there were ≥4 missing out of the 7 daily total scores.	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 749 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 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.	up to 960 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 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.	up to 960 days
Time of Onset of a ≥35% Reduction in Spleen Volume	The time to the first ≥35% reduction in spleen volume is defined as the time from randomization to the first time participants had ≥35% reduction in spleen volume.	up to 925 days
Duration of Maintenance of a ≥35% Reduction in Spleen Volume	The duration of ≥35% reduction from Baseline in spleen volume was defined as the interval between the first spleen volume measurement that was a ≥35% reduction from Baseline and the date of the first measurement that was no longer a ≥35% reduction from Baseline.	up to 925 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 24, 2021
• Primary Completion (Actual): August 3, 2023
• Study Completion (Actual): November 25, 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 21, 2025
• Last Update Submitted That Met QC Criteria: October 6, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Myeloproliferative Neoplasms; Myelofibrosis; MF; ruxolitinib; LIMBER; INCB050465; parsaclisib; Myoproliferative Neoplasms
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis; ruxolitinib; parsaclisib
• Other Study ID Numbers: INCB 50465-313/LIMBER-313; 2020-003130-21 (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