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

JRCT ID: jRCT2031210445

Registered date:24/11/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Anemia, Post-essential Thrombocythemia Myelofibrosis, Post-polycythemia Vera Myelofibrosis
• Date of first enrollment: 27/05/2022
• Target sample size: 206
• Countries of recruitment: U.S.A,Japan,France,Japan,Italy,Japan,Canada,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

Sequential Assignment
1.Treatment Group A (TGA)
INCB000928 will be administered once daily (QD).
2.Treatment Group B (TGB)
INCB000928 will be administered in combination with ruxolitinib.
3.Treatment Group C (TGC)
INCB000928 will be administered in combination with ruxolitinib.

Outcome(s)

Primary Outcome

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).

Secondary Outcome

1.Anemia Response
2.Duartion of Anemia Response
3.Mean Change of Hemoglobin
4.Rate of RBC transfusion
5.TGB and TGC only - Splenic Volume
6.TGB and TGC only - Splenic Length
7.TGB and TGC only - Objective Response Rate
8.TGB and TGC only - Progression Free Survival
9.TGB and TGC only - Leukemia Free Survival
10.AUC; area under the plasma concentration versus time curve of INCB 00928-104
11.Tmax; time to reach maximum (peak) plasma concentration of INCB 00928-104
12.AUC0-t; area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
13.Hepcidin levels
14.Iron Homeostasis
15.Erythropoesis

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable

Include criteria

1.Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows:
a.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).
b.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.
2.ECOG performance status score of the following:
a.0 or 1 for the dose-escalation stages.
b.0, 1, or 2 for the dose-expansion stage.
3.Life expectancy is greater than 6 months
4.Agreement to avoid pregnancy or fathering children.
5.Ineligible to receive or have not responded to available therapies for anemia such as ESAs.
6.For TGA:
a.Participants previously treated with JAK inhibitors for at least 12 weeks.
b.Participants with intermediate-2 or high DIPSS MF according to IWG-MRT criteria.
7.For TGB:
a.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.
b.Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.
8.For TGC:
a.Participants must be JAK inhibitor treatment naive (no prior treatment with any JAK inhibitor) and have an indication for initiation of ruxolitinib treatment.
b.Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.

Exclude criteria

1.Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
2.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.
3.Laboratory Values outside of protocol defined range at screening.

Related Information

• Primary Sponsor: Suzukawa Kazumi
• Secondary ID(s): NCT04455841,