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

NCT04455841 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 3 other identifiers: INCB 00928-1042023-503625-19-002020-004029-21
• Study Type: interventional
• Target: 84
• Locations: 6 countries
• Sites: 34

Brief Summary

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.

Conditions

Anemia; Post-essential Thrombocythemia Myelofibrosis; Post-polycythemia Vera Myelofibrosis

Keywords

anemia

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE)

  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. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug/treatment. A TEAE was 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 days after the last dose of study drug.

  up to approximately 4 years

• Number of Participants With Any ≥Grade 3 TEAE and Any Treatment-emergent SAE

  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. A TEAE was 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 days after the last dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

  up to approximately 4 years

• Number of Participants With Dose-limiting Toxicities (DLTs)

  A DLT was defined as the occurrence of any protocol-defined toxicity occurring during the first treatment cycle, from Cycle 1 Day 1 up to and including Cycle 1 Day 28 (per regimen cycle schedule), except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. The DLT-Evaluable Population included all non-backfill participants eligible for dose escalation who met the criteria outlined in the Analysis Population field.

  from Cycle 1 Day 1 to Cycle 1 Day 28

• Maximum Tolerated Dose (MTD)

  The MTD was defined as the dose at which the observed DLT rate was closest to the target DLT rate of 28% using an isotonical method that took the assumption of a monotonic dose-toxicity relationship into account. Per the protocol, the stopping rule was either (a) reaching a certain number of participants at one dose level under the early stopping rule or (b) reaching the pre-defined maximum sample size. Dose escalation was to be considered complete only when one of these conditions was met. After completion, the MTD was to be defined as the dose level closest to the target DLT rate. The MTD could not be concluded until the stopping rule was met.

  from Cycle 1 Day 1 to Cycle 1 Day 28

• Recommended Dose for Expansion (RDE)

  The RDE was defined as a pharmacodynamically active dose. The RDE was determined in an independent fashion by evaluation of all available data (i.e., safety, pharmacokinetic, and pharmacodynamic data) from the respective dose-escalation stage of the study for further investigation in the expansion cohort, including safety (e.g., low-grade but chronic toxicities, dose reduction, dose interruption, or missed doses of zilurgisertib and/or ruxolitinib). The RDE(s) could not exceed the MTD in each treatment group

  from Cycle 1 Day 1 to Cycle 1 Day 28

Secondary Outcomes (15)

• Percentage of Participants With Anemia Response

  up to Week 24

• Duration of Anemia Response

  up to 1530 days

• Mean Change From Baseline in the Hgb Value Over 12-week Treatment Periods

  Baseline; up to 24 weeks

• Rate of Red Blood Cell (RBC) Transfusion From Week 24 Through Week 48

  from Week 24 through Week 48

• Splenic Volume Response Rate at Week 24

  Week 24

Study Arms (3)

Treatment Group A (TGA)

EXPERIMENTAL

INCB000928 will be administered once daily (QD).

Drug: INCB000928

Treatment Group B (TGB)

EXPERIMENTAL

INCB000928 will be administered in combination with ruxolitinib.

Drug: INCB000928; Drug: ruxolitinib

Treatment Group C (TGC)

EXPERIMENTAL

INCB000928 will be administered in combination with ruxolitinib.

Drug: INCB000928; Drug: ruxolitinib

Interventions

INCB000928 DRUG

INCB000928 will be administered at protocol defined dose.

Treatment Group A (TGA); Treatment Group B (TGB); Treatment Group C (TGC)

ruxolitinib DRUG

Ruxolitinib will be administered at protocol defined dose.

Treatment Group B (TGB); Treatment Group C (TGC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows:
• 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).
• 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:
• or 1 for the dose-escalation stages.
• , 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (34)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

City of Hope Orange County

Irvine, California, 92618, United States

Location

Usc Norris Comprehensive Cancer Center

Los Angeles, California, 90089, United States

Location

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

Prebys Cancer Center

San Diego, California, 92103, United States

Location

Emory University - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory University-Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Start Midwest

Grand Rapids, Michigan, 49546, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medical Centers

New York, New York, 10065, United States

Location

Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy

Durham, North Carolina, 27705, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Centre Hospitalier D'Angers

Angers, 49033, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Hospital Saint Louis

Paris, 75010, France

Location

Azienda Ospedaliera Papa Giovanni Xxiii

Bergamo, 24127, Italy

Location

S Orsolas University Hospital Seragnoli Institute of Hematology

Bologna, 40138, Italy

Location

Azienda Ospedaliero-Universitaria Careggi (Aouc)

Florence, 50134, Italy

Location

Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano

Orbassano, 10043, Italy

Location

Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo

Pavia, 27100, Italy

Location

Ospedale Santa Maria Della Misericordia Perugia

Perugia, 06124, Italy

Location

Tokyo Medical and Dental University Hospital

Bunkyō City, 113-8519, Japan

Location

Chiba Cancer Center

Chiba, 260-8717, Japan

Location

Gifu Municipal Hospital

Gifu, 500-8513, Japan

Location

Kansai Medical University Hospital

Hirakata, 573-1191, Japan

Location

Kumamoto Shinto General Hospital

Kumamoto, 862-8655, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

University Hospital of Wales

Cardiff, WLS, CF14 4XW, United Kingdom

Location

United Lincolnshire Hospitals

Boston, PE21 9QS, United Kingdom

Location

Lincoln County Hospital

Lincoln, LN2 5QY, United Kingdom

Location

Royal Cornwall Hospital Truro Sunrise Centre

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (1)

• Gangat N, Tefferi A. Targeting anemia in myeloid neoplasms. Am J Hematol. 2024 Sep;99(9):1663-1666. doi: 10.1002/ajh.27408. Epub 2024 Jun 5.

  PMID: 38837732 DERIVED

Related Links

• Related Info
• INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders

MeSH Terms

Conditions

Anemia

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Enrollment in this study was closed following a strategic decision, not based on safety concerns, to discontinue the development of zilurgisertib for the treatment of anemia in myeloproliferative disorders.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Amanda McBride, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2020
• First Posted: July 2, 2020
• Study Start: March 19, 2021
• Primary Completion: April 1, 2025
• Study Completion (Estimated): November 26, 2027
• Last Updated: May 14, 2026
• Results First Posted: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• 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.

Locations

IT (6); JP (6); FR (3); GB (4); US (13); CA (2)