This phase 1b/2a open-label study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of DISC-0974 as well as categorize the effects on hematologic response in participants with myelofibrosis or myelodysplastic syndrome and anemia.
Age 18 years or older at the time of signing the informed consent form (ICF).
For Phase 1b: Dynamic International Prognostic Scoring System (DIPSS) score of 3 to 4 (intermediate 2 risk) or ≥5 (high-risk) primary MF, post PV MF, and/or post ET MF, as confirmed in the most recent local bone marrow biopsy report, according to World Health Organization (WHO) 2016 criteria.
Androgens
EPO
Hereditary hemochromatosis
Hemoglobinopathy or intrinsic RBC defect associated with anemia
Total splenectomy
Hematopoietic cell transplant within the past 2 years, or graft vs host disease requiring immunosuppression
Sequential
DISC-0974
DrugDISC-0974 is administered subcutaneously.
Safety and Tolerability of DISC-0974 (Phase 1b only)
Assessed by treatment-emergent adverse events
Safety and Tolerability of DISC-0974 (Phase 1b only)
Assessed by vital signs through blood pressure (mmHg), heart rate (bpm), respiration rate (breaths/min), and temperature (°C)
Safety and Tolerability of DISC-0974 (Phase 1b only)
Assessed by physical examinations
Safety and Tolerability of DISC-0974 (Phase 1b only)
Assessed by electrocardiogram (ECG) parameters: heart rate, PR interval, QRS duration, QRS axis, QT interval, and QTcF interval)
Anemia response defined per IWG-MRT 2006 criteria (Phase 1b only)
Response in nTD participants is defined as ≥2.0 g/dL increase from baseline in Hgb levels. Response in TD participants requires absence of PRBC transfusions during any rolling 12-week period during the treatment period, capped by an Hgb level of ≥8.5 g/dL.
TD high and TD low participants will be evaluated for absence of PRBC transfusions for any rolling 12-week interval during the treatment period (Phase 1b only)
TD high participants will be evaluated for absence of PRBC transfusions with minimum Hgb of 7 g/dL during any rolling 12-week interval during the treatment period (Phase 1b only)
TD low participants will be evaluated for absence of PRBC transfusions with minimum Hgb of 7 g/dL during any rolling 16-week interval during the treatment period (Phase 1b only)
Cmax (Phase 1b, 2, and Exploratory Cohorts)
Maximum drug concentration (observed). Will be determined from blood PK sampling if appropriate data are available
Tmax (Phase 1b, 2, and Exploratory Cohorts)
Observed time of the maximum drug concentration. Will be determined from blood PK sampling if appropriate data are available
AUC (Phase 1b, 2, and Exploratory Cohorts)
Area under the drug concentration-time curve calculated using linear trapezoidal summation from time zero to 29 days following the first dose. Will be determined from blood PK sampling if appropriate data are available.
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