Study of DISC-0974 in Participants with Myelofibrosis or Myelodysplastic Syndrome and Anemia
Phase 1
Recruiting
- Conditions
- Myelofibrosis; AnemiaMyelofibrosisMyelofibrosis Due to and Following Polycythemia VeraPrimary MyelofibrosisAnemiaPost-essential Thrombocythemia MyelofibrosisMyelodysplastic Syndromes
- Interventions
- Registration Number
- NCT05320198
- Lead Sponsor
- Disc Medicine, Inc
- Brief Summary
This phase 1b/2a open-label study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of DISC-0974 as well as categorize the effects on anemia response in subjects with myelofibrosis or myelodysplastic syndrome and anemia.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1b: Dose Escalation DISC-0974 In the Phase 1b (dose-escalation) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks. Phase 2: Expansion DISC-0974 In the Phase 2 (expansion) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks.
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (Phase 1b only) up to 225 days Incidence of clinically abnormal vital signs (Phase 1b only) up to 225 days Incidence of clinically abnormal physical exam (Phase 1b only) up to 225 days Incidence of clinically abnormal electrocardiograms (Phase 1b only) up to 225 days Incidence of abnormal laboratory test results (Phase 1b only) up to 225 days Transfusion-dependent (TD) high cohort: transfusion independence, defined as the absence of packed red blood cell (PRBC) transfusions over any rolling 12-week interval during the treatment period with a minimum hemoglobin (Hgb) of 7 g/dL (Phase 2 only) up to 225 days TD low cohort: transfusion independence, defined as the absence of PRBC transfusions over any rolling 16 week interval during the treatment period with a minimum Hgb of 7 g/dL (Phase 2 only) up to 225 days Non-transfusion-dependent (nTD) cohort: anemia response, defined as the composite of the absence of transfusions over any rolling 12 week period and a concomitant mean Hgb increase of ≥1.5 g/dL over baseline (Phase 2 only) up to 225 days
- Secondary Outcome Measures
Name Time Method Anemia response defined per IWG-MRT criteria (Phase 1b only) up to 225 days TD high and TD low participants will be evaluated for absence of PRBC transfusions for a consecutive, "rolling" 12 week interval during the treatment period (Phase 1b only) up to 225 days TD high participants will be evaluated for absence of PRBC transfusions with minimum Hgb of 7 g/dL during a terminal 12 week interval during the treatment period (Phase 1b only) up to 225 days 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) up to 225 days nTD participants will be evaluated for ≥1.5 g/dL increase from baseline Hgb levels during the treatment period (Phase 1b only) up to 225 days nTD participants will be evaluated for the composite of the absence of transfusions over any rolling 12 week period and a concomitant mean Hgb increase of ≥1.5 g/dL over baseline (Phase 1b only) up to 225 days Safety, tolerability, PK, and PD of DISC-0974 following repeated SC doses in participants with myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) without excess blasts (collectively referred to as MDS) and anemia (Phase 1b only) up to 225 days Proportion of participants achieving a mean Hgb increase ≥1 g/dL or ≥2 g/dL from baseline over any rolling 12-week period in absence of RBC transfusions in each cohort (Phase 1b and 2) up to 225 days Change from baseline in concentration of iron laboratory parameters (Phase 1b and 2) up to 225 days Change from baseline in concentration of hematologic laboratory parameters (Phase 1b and 2) up to 225 days Rate and units of RBC transfusion per participant month during the treatment period for each cohort (Phase 1b and 2) up to 225 days Transfusion-dependent cohorts will be evaluated for proportion of participants who reduce their transfusion requirement by 50%, compared to baseline, over any rolling 12-week period during treatment (Phase 1b and 2) up to 225 days nTD participants will be evaluated for longest duration of mean Hgb increase of ≥1.5 g/dL from baseline during the treatment period (Phase 1b and 2) up to 225 days Mean change in Hgb over 12-week treatment periods will be evaluated for all cohorts (nTD, TD low, TD high) (Phase 1b and 2) up to 225 days Maximum duration of RBC-transfusion-independent response for TD participants (Phase 1b and 2) up to 225 days Proportion of participants that require dose escalation in each cohort (Phase 1b and 2) up to 225 days Proportion of participants that improve Functional Assessment of Cancer Therapy-Anemia (FACT-An) subscale by at least 3 points in each cohort during the treatment period (Phase 1b and 2) up to 225 days Mean hemoglobin increase of ≥1.5 g/dL over a rolling 12-week interval and an increase in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue of 3 points by the end of study (EOS) for nTD participants (Phase 1b and 2) up to 225 days TD high cohort will be evaluated for absence of packed red blood cell (PRBC) transfusions a terminal 12 week interval during the treatment period with a minimum hemoglobin (Hgb) of 7 g/dL (Phase 1b and 2) up to 225 days TD low cohort: will be evaluated for the absence of PRBC transfusions a terminal 16 week interval during the treatment period with a minimum Hgb of 7 g/dL (Phase 1b and 2) up to 225 days Non-transfusion-dependent (nTD) cohort: anemia response, defined as the composite of the absence of transfusions over any rolling 12 week period and a concomitant mean Hgb increase of ≥1.5 g/dL over baseline (Phase 1b and 2) up to 225 days Incidence of treatment-emergent adverse events (Phase 2 only) up to 225 days Incidence of clinically abnormal vital signs (Phase 2 only) up to 225 days Incidence of clinically abnormal physical exam (Phase 2 only) up to 225 days Incidence of clinically abnormal electrocardiogram (Phase 2 only) up to 225 days Incidence of abnormal laboratory test results (Phase 2 only) up to 225 days Safety and tolerability of DISC-0974 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib therapy as assessed by TEAEs, vital signs, physical examinations, ECGs, and blood and urine testing (Phase 2 only) 225 days Cmax-Maximum drug concentration measured in plasma (Phase 1b and 2) up to 225 days Tmax-Time of maximum drug concentration (Phase 1b and 2) up to 225 days AUC-Area under the drug concentration time curve (Phase 1b and 2) up to 225 days Additional PK analysis using a population PK analysis approach may be considered. (Phase 1b and 2) up to 225 days
Trial Locations
- Locations (15)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Washington University St.Louis
🇺🇸St. Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Atrium Health Wake Forest Baptist
🇺🇸Winston-Salem, North Carolina, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Sargon Research - Pennsylvania Cancer Specialists and Research Center
🇺🇸Gettysburg, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
MD Anderson
🇺🇸Houston, Texas, United States
University of Washington
🇺🇸Seattle, Washington, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States