Clinical Trials /

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

NCT04582539

Description:

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.

Related Conditions:
  • Chronic Myelomonocytic Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: INCB 00928-105
  • NCT ID: NCT04582539

Conditions

  • Myelodysplastic Syndromes
  • Multiple Myeloma
  • Anemia

Interventions

DrugSynonymsArms
INCB000928INCB000928

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
INCB000928ExperimentalINCB000928 will be administered in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.
  • INCB000928

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of treatment-related adverse events
Time Frame:Approximately up to 7 months
Safety Issue:
Description:To determine the safety and tolerability of INCB000928 administered as monotherapy in participants with MDS or MM.

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Myelodysplastic Syndromes
  • Multiple Myeloma
  • Anemia

Last Updated

June 10, 2021