To Assess the Safety and Tolerability of INCB000928 in Participants With Myelodysplastic Syndromes or Multiple Myeloma.

Sponsor

Incyte Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04582539

Collaborator

(none)

Enrollment

Locations

Arm

23.3

Anticipated Duration (Months)

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 in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes Multiple Myeloma Anemia	Drug: INCB000928	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

N/A

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 in Participants With Anemia Due to Myelodysplastic Syndromes or Multiple Myeloma

Actual Study Start Date :

Aug 19, 2021

Anticipated Primary Completion Date :

Jul 28, 2023

Anticipated Study Completion Date :

Jul 28, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INCB000928 INCB000928 will be administered in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.	Drug: INCB000928 INCB000928 will be administered once daily.

Arm

Intervention/Treatment

Experimental: INCB000928

INCB000928 will be administered in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.

Drug: INCB000928

INCB000928 will be administered once daily.

Outcome Measures

Primary Outcome Measures

Number of treatment-related adverse events [Approximately up to 7 months]
To determine the safety and tolerability of INCB000928 administered as monotherapy in participants with MDS or MM.

Secondary Outcome Measures

Proportion of participants with anemia response (for TI patients at baseline) [Approximately up to 7 months]
Defined as an Hgb increase.
Duration of anemia response [Approximately up to 7 months]
Defined as the interval from the first onset of anemia response to the earliest date of loss of anemia response.
Proportion of participants with RBC-TI (for TD at baseline) [Approximately up to 7 months]
Defined as the absence of any RBC transfusion
Duration of RBC-TI period [Approximately up to 7 months]
Defined as duration of time for which participants are transfusion independent
Rate of RBC transfusion [Through weeks 12 and 24]
Defined as the average number of RBC units
Increase in mean Hgb [Approximately up to 7 months]
Defined as the increase from baseline in the mean Hgb
MDS Participants only : Overall Response Rate [Approximately up to 7 months]
Defined as the proportion of participants with CR or PR
MDS Participants only : Progression Free Survival [Approximately up to 7 months]
Defined as the interval from the first dose of study drug until the first documented progression or death
MDS Participants only : Leukemia Free Survival [Approximately up to 7 months]
Defined as the interval from the first dose of study drug until the first documented leukemia transformation or death from any cause.
MM participants only : Overall Response Rate [Approximately up to 7 months]
Defined as the proportion of participants with stringent CR, CR, very good PR, and PR
MM Participants only : Progression Free Survival [Approximately up to 7 months]
Defined as the interval from the first dose of study drug until the first documented progression or death.
Cmax [C1D1 and C1D15]
Maximum plasma concentration of INCB000928
Tmax [C1D1 and C1D15]
Time to reach maximum (peak) plasma concentration of INCB000928
AUC0-t [C1D1 and C1D15]
Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Hepcidin levels [Approximately upto 7 months]
Effect of INCB000928 on hepcidin levels
Iron Homeostasis [Approximately upto 7 months]
Effect of INCB000928 on iron homeostasis.
Erythropoiesis [Approximately upto 7 months]
Effect of INCB000928 on erythropoiesis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Agreement to avoid pregnancy or fathering children.
Participants who are transfusion-dependent or present with symptomatic anemia

For MDS participants:

Ineligible to receive or have not responded to available therapies for anemia such as ESAs or lenalidomide.
Not requiring cytoreductive therapy other than hydroxyurea.
BM and peripheral blood myeloblast count < 10%.
Histologically confirmed diagnosis of the MDS, CMML and unclassifiable MDS/MPN overlap syndromes.

For MM participants:

Histologically confirmed diagnosis of MM.
After failure of available standard treatments such as alkylating agents, glucocorticoids, immunomodulatory drugs (lenalidomide,pomalidomide, or thalidomide), proteasome inhibitors (bortezomib or carfilzomib), and daratumumab.

Exclusion Criteria:

Any prior allogeneic stem cell transplantation or a candidate for such transplantation.
Any major surgery within 28 days before the first dose of study drug.
Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, or antibody or hypomethylating agent to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug.
Undergoing treatment with another investigational medication or having been treated with an investigational medication within 28 days before the first dose of study drug. -Undergoing treatment with ESAs, granulocyte colony-stimulating factor or granulocyte/macrophage colony-stimulating factor, romiplostin, or eltrombopag at any time within 28 days before the first dose of study drug.
Undergoing treatment with a strong or potent inhibitor or inducer of CYP3A4/5 within 28 days or 5 half-lives (whichever is longer) before the first dose of study drug or expected to receive such treatment during the study.
History of clinically significant or uncontrolled cardiac disease.
History or presence of an abnormal ECG that, in the investigator's opinion, is clinically Meaningful.
Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment.
Diagnosis of chronic liver disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	Stanford Cancer Center	Palo Alto	California	United States	94304
3	University of Miami	Miami	Florida	United States	33136
4	Tulane Comprehensive Cancer Center	New Orleans	Louisiana	United States	70112
5	Barbara Ann Karmanos Cancer Hospital	Detroit	Michigan	United States	48201
6	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
7	University of Cincinnati	Cincinnati	Ohio	United States	45219
8	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
9	Md Anderson Cancer Center	Houston	Texas	United States	77030
10	Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu	Nantes		France	44093
11	Hospices Civils de Lyon Centre Hospitalier Lyon Sud	Pierre Benite		France	69310
12	Institut Gustave Roussy	Villejuif		France	94800
13	L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA ï¿½ MALPIGHI	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	Irccs Istituto Clinico Humanitas	Rozzano		Italy	20089