Clinical Trials/NCT05320198

NCT05320198

Recruiting

Phase 1

RALLY-MF: A Phase 1b/2 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of DISC-0974 in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia

Disc Medicine, Inc35 sites in 2 countries150 target enrollmentJune 6, 2022

ConditionsMyelofibrosis; Anemia Anemia Myelofibrosis Myelofibrosis Due to and Following Polycythemia Vera Primary Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Myelodysplastic Syndromes

InterventionsDISC-0974

DrugsDISC-0974

Overview

Phase: Phase 1
Intervention: DISC-0974
Conditions: Myelofibrosis; Anemia
Sponsor: Disc Medicine, Inc
Enrollment: 150
Locations: 35
Primary Endpoint: Incidence of treatment-emergent adverse events (Phase 1b only)
Status: Recruiting
Last Updated: yesterday

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

June 6, 2022

End Date

September 1, 2026

Last Updated

yesterday

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Disc Medicine, Inc

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•for Participants with MF and Anemia
•Participants are eligible for the study if all of the following criteria apply:
•Age 18 years or older at the time of signing the informed consent form (ICF).
•For Phase 1b: 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 WHO 2016 criteria.55
•For Phase 2: In addition to the criteria above, DIPSS score of ≥2 (intermediate 1 risk) may also be included.
•Washout of at least 28 days prior to Screening of the following treatments:
•Immunomodulators (lenalidomide, thalidomide)
•Luspatercept/sotatercept
•Systemic corticosteroids are permitted for non-hematological conditions if stable or decreasing dose for ≥28 days prior to Screening and receiving an equivalent to ≤10 mg prednisone for the 28 days immediately prior to Screening.
•Screening can begin before the 28 day washout is completed, but the washout period must be completed prior to collection of Screening blood samples.

Exclusion Criteria

•Exclusion Criteria for Participants with MF and Anemia
•Participants are excluded from the study if any of the following criteria apply:
•Medical History, Participants with MF and Anemia
•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
•Current anemia from iron deficiency, vitamin B12 or folate deficiency, infection, or bleeding
•Active immune-mediated hemolytic anemia
•Symptomatic bleeding, unrelated to surgery, in a critical area or organ and/or bleeding causing a decrease in Hgb of ≥2 g/dL or leading to transfusion of ≥2 units of RBCs in the 6 months prior to Screening

Arms & Interventions

Phase 1b: Dose Escalation

In the Phase 1b (dose-escalation) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks.

Intervention: DISC-0974

Phase 2: Expansion

In the Phase 2 (expansion) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks.

Intervention: DISC-0974

Outcomes

Primary Outcomes

Incidence of treatment-emergent adverse events (Phase 1b only)

Time Frame: up to 225 days

Incidence of clinically abnormal vital signs (Phase 1b only)

Time Frame: up to 225 days

Incidence of clinically abnormal physical exam (Phase 1b only)

Time Frame: up to 225 days

Incidence of clinically abnormal electrocardiograms (Phase 1b only)

Time Frame: up to 225 days

Incidence of abnormal laboratory test results (Phase 1b only)

Time Frame: 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)

Time Frame: 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)

Time Frame: 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)

Time Frame: up to 225 days

Secondary Outcomes

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)