INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders (LIMBER)

A Phase 1/2 Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders

This Phase 1/2, open-label, dose-finding study is intended to evaluate the safety and tolerability, PK, PD, and efficacy of INCB000928 administered as monotherapy or in combination with ruxolitinib in participants with MF who are transfusion-dependent or presenting with symptomatic anemia. This study will consist of 2 parts: dose escalation and expansion.

Study Overview

• Status: Recruiting
• Conditions: Anemia; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
• Intervention / Treatment: Drug: INCB000928; Drug: ruxolitinib

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Incyte Corporation Call Center (US); Phone Number: 1.855.463.3463; Email: medinfo@incyte.com
• Study Contact Backup: Name: Incyte Corporation Call Center (ex-US); Phone Number: 1.855.463.3463; Email: globalmedinfo@incyte.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, MG5 2R2
      • Recruiting
      • Princess Margaret Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H3T1E2
      • Not yet recruiting
      • McGill University Jewish General Hospital
• France
  • Angers Cedex 01, France, 49033
    • Recruiting
    • Centre Hospitalier D'Angers
  • Marseille Cedex 9, France, 13273
    • Recruiting
    • Institut Paoli Calmettes
  • Paris, France, 75010
    • Recruiting
    • Hospital Saint Louis
• Italy
  • Bergamo, Italy, 24127
    • Recruiting
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • Recruiting
    • S Orsolas University Hospital Seragnoli Institute of Hematology
  • Firenze, Italy, 50134
    • Recruiting
    • Azienda Ospedaliero-Universitaria Careggi (Aouc)
  • Orbassano, Italy, 10043
    • Not yet recruiting
    • Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
  • Pavia, Italy, 27100
    • Completed
    • Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
  • Perugia, Italy, 06124
    • Recruiting
    • Ospedale Santa Maria Della Misericordia Perugia
• Japan
  • Bunkyo-ku, Japan, 113-8519
    • Recruiting
    • Tokyo Medical and Dental University Hospital
  • Chiba, Japan, 260-8717
    • Recruiting
    • Chiba Cancer Center
  • Gifu, Japan, 500-8513
    • Recruiting
    • Gifu Municipal Hospital
  • Hirakata, Japan, 573-1191
    • Recruiting
    • Kansai Medical University Hospital
  • Kumamoto, Japan, 862-8655
    • Recruiting
    • Kumamoto Shinto General hospital
  • Osaka-shi, Japan, 541-8567
    • Recruiting
    • Osaka International Cancer Institute
• United Kingdom
  • Boston, United Kingdom, PE21 9QS
    • Not yet recruiting
    • United Lincolnshire Hospitals
  • Lincoln, United Kingdom, LN2 5QY
    • Not yet recruiting
    • Lincoln County Hospital
  • Truro, United Kingdom, TR1 3LQ
    • Recruiting
    • Royal Cornwall Hospital Truro Sunrise Centre
  • WLS
    • Cardiff, WLS, United Kingdom, CF14 4XW
      • Recruiting
      • University Hospital of Wales
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope Orange County
    • Los Angeles, California, United States, 90089
      • Recruiting
      • USC Norris Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Center
    • San Diego, California, United States, 92103
      • Not yet recruiting
      • Prebys Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University - Winship Cancer Institute
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University-Winship Cancer Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medical Centers
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows:

  1. Anemia: An Hgb value < 10 g/dL demonstrated during screening recorded on 3 separate occasions with at least 7 days between measurements (Note: RBC transfusion must be at least 2 weeks before the Hgb measurement during screening).
  2. Transfusion-dependent: Participant has received at least 4 units of RBC transfusions during the 28 days immediately preceding Cycle 1 Day 1 OR has received an average of at least 4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for an Hgb level of < 8.5 g/dL, in the absence of bleeding or treatment-induced anemia. In addition, the most recent transfusion episode must have occurred in the 28 days before Cycle 1 Day 1.

• ECOG performance status score of the following:

  1. 0 or 1 for the dose-escalation stages.
  2. 0, 1, or 2 for the dose-expansion stage.
• Life expectancy is greater than 6 months
• Agreement to avoid pregnancy or fathering children.
• Ineligible to receive or have not responded to available therapies for anemia such as ESAs.
• For TGA:
• Participants previously treated with JAK inhibitors for at least 12 weeks.
• Participants with intermediate-2 or high DIPSS MF according to IWG-MRT criteria.
• For TGB:
• Participants must have been on a therapeutic and stable regimen of ruxolitinib for at least 12 consecutive weeks immediately preceding the first dose of study treatment.
• Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.

Exclusion Criteria:

• Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
• Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib for TGB only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• Laboratory Values outside of protocol defined range at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group A (TGA); INCB000928 will be administered once daily( QD).	Drug: INCB000928; INCB000928 Dose Escalation
Experimental: Treatment Group B (TGB); INCB000928 will be administered in combination with ruxolitinib.	Drug: INCB000928; INCB000928 Dose Escalation; Drug: ruxolitinib; INCB000928 +ruxolitinib Dose Expansion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-related adverse events	To determine the safety and tolerability of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB).	Approximately up to 13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anemia Response	Defined as an increase in hemoglobin.	Approximately up to 13 months
Duration of Anemia Response	Duration of anemia response at baseline.	Approximately up to 13 months
Mean Change of Hemoglobin	Mean change in hemoglobin levels from baseline	Approximately up to 13 months
Rate of RBC transfusion	Defined as the average number of RBC units	Approximately up to 13 months
TGB only -Splenic Volume	Defined as the proportion of participants achieving a targeted reduction in spleen volume	Approximately up to 13 months
TGB Only - Splenic Length	Defined as the proportion of participants achieving a targeted reduction in spleen length	Approximately Up to 13 months
TGB only - Objective Response Rate	defined as the proportion of participants with Complete Response or Partial Response	Approximately up to 13 months
TGB only - Progression Free Survival	Defined as the interval from the first dose of study treatment until the first documented progression or death	Approximately up to 13 months
TGB only - Leukemia Free Survival	defined as the interval from the first dose of study treatment until the first documented leukemia transformation or death from any cause	Approximately upto 13 months
AUC	Area Under the Plasma Concentration versus Time curve of INCB 00928-104	Approximately up to 13 months
Tmax	Time to reach maximum (peak) plasma concentration of INCB 00928-104	Approximately up to 13 months
AUC0-t	Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.	Approximately up to 13 months
Hepcidin levels	Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB) on hepcidin levels	Approximately up to 13 months
Iron Homeostasis	Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB) on iron homeostasis parameters such as TSI, ferritin, transferrin, TSAT, TIBC, UIBC, and serum NTBI.	Approximately up to 13 months
Erythropoesis	Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB) on erythropoiesis parameters such as RC, NRBC, MCV, MCH, Hgb, Hct, RBC count, MCHC, and RDW.	Approximately up to 13 months

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Ekatarine Asantiani, MD, Incyte Corporation

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: LIMBER
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Anemia; Myeloproliferative Disorders; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: INCB 00928-104

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