Participants who are transfusion-dependent or present with symptomatic anemia
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to comprehend and willingness to sign a written ICF for the study. 2. Age 18 years or older at the time of signing the ICF. 3. ECOG performance status of the following: a. 0 or 1 for the dose-escalation stages. b. 0, 1, or 2 for the dose-expansion stage. 4. Life expectancy > 6 months. 5. Agreement to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children from screening through 90 days after the last dose of study drug and must refrain from donating sperm during this period. b. Women with childbearing potential must have a negative serum pregnancy test at screening before the first dose must agree to take appropriate precautions to avoid pregnancy from screening through the safety follow-up visit, and must not donate oocytes during this period. c. Women without childbearing potential are eligible. 6. Participants who are transfusion-dependent or present with symptomatic anemia, defined as follows: a. Anemia: an Hgb value =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Any prior allogeneic stem cell transplantation or a candidate for such transplantation. 2. Any major surgery within 28 days before the first dose of study drug. 3. 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. a. Exceptions include glucocorticoids and hydroxyurea 4. Undergoing treatment with another investigational medication or having been treated with an investigational medication within 28 days before the first dose of study drug. 5. 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. 6. 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 7. Any prior radiation therapy within 28 days before the first dose of study drug. 8. Presence of any hematologic malignancy other than MDS or MM, as applicable. 9. Active invasive malignancy over the previous 5 years 10. Known active disease involving the CNS. 11. History of clinically significant or uncontrolled cardiac disease 12. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. 13. Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. 14. Diagnosis of chronic liver disease 15. Known active hepatitis A, HBV, or HCV infection or known HIV infection. 16. Unwillingness to be undergo transfusion with blood components, including RBC packs and platelet transfusions. 17. Any condition in the investigator's judgment that would interfere with full participation in the study including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. 18. Active alcohol or drug addiction that would interfere with the participant's ability to comply with the study requirements. 19. Gastroesophageal reflux disease not controlled by medication within 28 days before the first dose of study drug. 20. Presence of any unresolved toxicity = Grade 2 from previous therapy except for stable chronic toxicities (= Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy. 21. Known hypersensitivity, severe reaction, or any known contraindications to the use of any of the active substances or excipients in INCB000928. 22. Women who are pregnant or breastfeeding. 23. Unable to swallow and retain oral medication. 24. Current use of prohibited medication 25. Participants with laboratory values at screening as defined in the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and tolerability of INCB000928 monotherapy in participants with MDS or MM.;Secondary Objective: To determine the efficacy of INCB000928 in participants with MDS or MM. To evaluate the PK of INCB000928 in participants with MDS or MM. To evaluate the effect of INCB000928 on the iron homeostasis and the erythropoiesis parameters in participants with MDS or MM.;Primary end point(s): • Frequency and severity of AEs and SAEs, including changes in vital signs, ECGs, physical examinations,and clinical blood and urine laboratory parameters. • Identification of the DLTs, MTD, and RDE.;Timepoint(s) of evaluation of this end point: Safety and endpoint assessments will be performed throughout the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • For transfusion-independent participants at baseline: - The proportion of participants with anemia response, defined as an Hgb increase of at least 1.5 g/dL relative to baseline for any 8-week period (with each assessment meeting this requirement) during the first 24 weeks of treatment. - Duration of anemia response, defined as the interval from the first onset of anemia response to the earliest date of loss of anemia response that persists for at least 4 weeks or death from any cause. • For transfusion-dependent participants at baseline: - The proportion of participants with RBC-TI, defined as the absence of any RBC transfusion for at least 8 consecutive weeks during the first 24 weeks of treatment. - Duration of RBC-TI period for participants achieving RBC-TI for at least 8 consecutive weeks during the first 24 weeks of treatment. • Rate of RBC transfusion through Weeks 12 and 24, defined as the average number of RBC units per participant-month during the treatment period. • The largest increase from baseline in the mean Hgb values over any rolling 8-week treatment period during the first 24 weeks of treatment. For MDS participants only: • Overall response rate, defined as the proportion of participants with CR or PR as per Cheson et al (2006) definitions for MDS and as per Savona et al (2015) definitions for MDS/MPN overlap syndromes, as applicable. • PFS, defined as the interval from the first dose of study drug until the first documented progression or death as per Cheson et al (2006) definitions for MDS and as per Savona et al (2015) definitions for MDS/MPN overlap syndromes. • LFS, defined as the interval from the first dose of study drug until the first documented leukemia transformation or death from any cause. For MM participants only: • Overall response rate, defined as the proportion of participants with stringent CR, CR, very good PR, and PR as per Kumar et al (2016). • PFS, defined as the interval from the firs | — |
Countries
France, Italy, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed