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

Sponsor

Incyte Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04455841

Collaborator

(none)

100

Enrollment

Locations

Arms

30.1

Anticipated Duration (Months)

4.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia Post-essential Thrombocythemia Myelofibrosis Post-polycythemia Vera Myelofibrosis	Drug: INCB000928 Drug: ruxolitinib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 19, 2021

Anticipated Primary Completion Date :

Sep 21, 2023

Anticipated Study Completion Date :

Sep 21, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Anemia Response [Approximately up to 13 months]
Defined as an increase in hemoglobin.
Duration of Anemia Response [Approximately up to 13 months]
Duration of anemia response at baseline.
Mean Change of Hemoglobin [Approximately up to 13 months]
Mean change in hemoglobin levels from baseline
Rate of RBC transfusion [Approximately up to 13 months]
Defined as the average number of RBC units
TGB only -Splenic Volume [Approximately up to 13 months]
Defined as the proportion of participants achieving a targeted reduction in spleen volume
TGB Only - Splenic Length [Approximately Up to 13 months]
Defined as the proportion of participants achieving a targeted reduction in spleen length
TGB only - Objective Response Rate [Approximately up to 13 months]
defined as the proportion of participants with Complete Response or Partial Response
TGB only - Progression Free Survival [Approximately up to 13 months]
Defined as the interval from the first dose of study treatment until the first documented progression or death
TGB only - Leukemia Free Survival [Approximately upto 13 months]
defined as the interval from the first dose of study treatment until the first documented leukemia transformation or death from any cause
AUC [Approximately up to 13 months]
Area Under the Plasma Concentration versus Time curve of INCB 00928-104
Tmax [Approximately up to 13 months]
Time to reach maximum (peak) plasma concentration of INCB 00928-104
AUC0-t [Approximately up to 13 months]
Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Hepcidin levels [Approximately up to 13 months]
Effect of INCB000928 administered as monotherapy (TGA) or in combination with ruxolitinib (TGB) on hepcidin levels
Iron Homeostasis [Approximately up to 13 months]
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.
Erythropoesis [Approximately up to 13 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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:

0 or 1 for the dose-escalation stages.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	Stanford Cancer Center	Palo Alto	California	United States	94304
3	Emory University - Winship Cancer Institute	Atlanta	Georgia	United States	30322
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	Weill Cornell Medical Centers	New York	New York	United States	10065
6	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
7	Md Anderson Cancer Center	Houston	Texas	United States	77030
8	Centre Hospitalier D'Angers	Angers Cedex 01		France	49033
9	Institut Paoli-Calmettes	Marseille Cedex 9		France	13273
10	Hospital Saint Louis	Paris		France	75010
11	Institut Gustave Roussy	Villejuif		France	94800
12	Azienda Ospedaliera Papa Giovanni Xxiii	Bergamo		Italy	24127
13	S Orsolas University Hospital Seragnoli Institute of Hematology	Bologna		Italy	40138
14	Azienda Ospedaliero-Universitaria Careggi (Aouc)	Firenze		Italy	50134
15	Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo	Pavia		Italy	27100
16	Tokyo Medical and Dental University Hospital	Bunkyo-ku		Japan	113-8519
17	Chiba Cancer Center	Chiba		Japan	260-8717
18	Gifu Municipal Hospital	Gifu		Japan	500-8513
19	Kansai Medical University Hospital	Hirakata		Japan	573-1191
20	Kumamoto Shinto General Hospital	Kumamoto		Japan	862-8655
21	Osaka International Cancer Institute	Osaka-shi		Japan	541-8567