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

Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04455841
• Other study ID #: INCB 00928-104
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 19, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 206
• Est. completion date: June 30, 2026
• Est. primary completion date: November 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• For TGC:

• Participants must be JAK inhibitor treatment naive (no prior treatment with any JAK inhibitor) and have an indication for initiation of ruxolitinib 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.

Related Conditions & MeSH terms

• Anemia
• Myeloproliferative Disorders
• Polycythemia
• Polycythemia Vera
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• INCB000928
INCB000928 will be administered at protocol defined dose.
• ruxolitinib
Ruxolitinib will be administered at protocol defined dose.

Locations

Country	Name	City	State
Canada	McGill University Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
France	Centre Hospitalier D'Angers	Angers Cedex 01
France	Institut Paoli Calmettes	Marseille Cedex 9
France	Hospital Saint Louis	Paris
Italy	Azienda Ospedaliera Papa Giovanni Xxiii	Bergamo
Italy	S Orsolas University Hospital Seragnoli Institute of Hematology	Bologna
Italy	Azienda Ospedaliero-Universitaria Careggi (Aouc)	Firenze
Italy	Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano	Orbassano
Italy	Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo	Pavia
Italy	Ospedale Santa Maria Della Misericordia Perugia	Perugia
Japan	Tokyo Medical and Dental University Hospital	Bunkyo-ku
Japan	Chiba Cancer Center	Chiba
Japan	Gifu Municipal Hospital	Gifu
Japan	Kansai Medical University Hospital	Hirakata
Japan	Kumamoto Shinto General Hospital	Kumamoto
Japan	Osaka International Cancer Institute	Osaka-shi
United Kingdom	United Lincolnshire Hospitals	Boston
United Kingdom	University Hospital of Wales	Cardiff	WLS
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	Royal Cornwall Hospital Truro Sunrise Centre	Truro
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	Emory University-Winship Cancer Institute	Atlanta	Georgia
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy	Durham	North Carolina
United States	Start Midwest	Grand Rapids	Michigan
United States	Md Anderson Cancer Center	Houston	Texas
United States	City of Hope Orange County	Irvine	California
United States	Usc Norris Comprehensive Cancer Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Weill Cornell Medical Centers	New York	New York
United States	Stanford Cancer Center	Palo Alto	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Prebys Cancer Center	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treatment-related adverse events	To determine the safety and tolerability of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC).	Approximately up to 13 months
Secondary	Anemia Response	Defined as an increase in hemoglobin.	Approximately up to 13 months
Secondary	Duration of Anemia Response	Duration of anemia response at baseline.	Approximately up to 13 months
Secondary	Mean Change of Hemoglobin	Mean change in hemoglobin levels from baseline.	Approximately up to 13 months
Secondary	Rate of RBC transfusion	Defined as the average number of RBC units.	Approximately up to 13 months
Secondary	TGB and TGC only -Splenic Volume	Defined as the proportion of participants achieving a targeted reduction in spleen volume.	Approximately up to 13 months
Secondary	TGB and TGC Only - Splenic Length	Defined as the proportion of participants achieving a targeted reduction in spleen length.	Approximately Up to 13 months
Secondary	TGB and TGC only - Objective Response Rate	Defined as the proportion of participants with Complete Response or Partial Response.	Approximately up to 13 months
Secondary	TGB and TGC 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
Secondary	TGB and TGC 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
Secondary	AUC	Area Under the Plasma Concentration versus Time curve of INCB 00928-104.	Approximately up to 13 months
Secondary	Tmax	Time to reach maximum (peak) plasma concentration of INCB 00928-104.	Approximately up to 13 months
Secondary	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
Secondary	Hepcidin levels	Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC) on hepcidin levels.	Approximately up to 13 months
Secondary	Iron Homeostasis	Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC) on iron homeostasis parameters such as TSI, ferritin, transferrin, TSAT, TIBC, UIBC, and serum NTBI.	Approximately up to 13 months
Secondary	Erythropoesis	Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB and TGC) on erythropoiesis parameters such as RC, NRBC, MCV, MCH, Hgb, Hct, RBC count, MCHC, and RDW.	Approximately up to 13 months

External Links

•   Related Info