Clinical Trial 23709

• Overview

  Study Title:

  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

  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.

  Objective:

  Primary Objective: Phase 1b Dose Escalation To assess the safety and tolerability of DISC-0974 following repeated SC doses in participants with primary MF, post-ET MF, or post-PV MF (collectively referred to as MF) and anemia. Phase 2 Expansion To characterize the effects of DISC-0974 on anemia response at the recommended Phase 2 dose (RP2D) in MF and anemia. Secondary Objectives: To characterize the repeat-dose PK of DISC-0974 in participants with MF. To characterize the relationship between DISC-0974 dose level and key biological indicators of mechanism engagement on iron and hematologic parameters. To assess the safety, tolerability, PK, and PD of DISC-0974 following repeated SC doses in participants with MDS or MDS/MPN without excess blasts (collectively referred to as MDS) and anemia (Phase 1b only). To assess the safety, tolerability, PK, and PD of DISC-0974 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib treatment (Phase 2 only).

• Treatments

  Therapies:

  Anti-HJV humanized monoclonal antibody

  Medications:

  DISC-0974 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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. 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: Androgens, EPO, Cladribine, 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.
  • Anemia: For Phase 1b: Hgb > Stable dosing of MF-directed therapy: Hydroxyurea, or, if taking any other treatment for MF, stable for at least 28 days prior to Screening. Interferon alpha stable dosing for at least 12 weeks prior to Screening. JAK inhibitors require 12 weeks of stable dosing prior to Screening. For the TD high, TD low, and nTD cohorts, JAK inhibitors allowed include momelotinib, pacritinib, fedratinib, and ruxolitinib. If the participant discontinues JAK inhibitor (including momelotinib/pacritinib/ruxolitinib/fedratinib) and/or hydroxyurea prior to Screening, a 60-day washout period is required.
  • Eastern Cooperative Oncology Group (ECOG) performance score ≤2.
  • Infusion of hematopoietic stem cell transplant not anticipated within 8 months after Screening.
  • TSAT > Liver iron concentration by MRI > Serum ferritin ≥50 µg/L at Screening.
  • Platelet count ≥25,000/µL and > Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula.
  • Aspartate aminotransferase (AST) and ALT > Direct bilirubin > Additional Criteria will apply

• Exclusion Criteria

  Key Exclusion Criteria:
  • 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
  • Major surgery within 8 weeks prior to Screening or incomplete recovery from any previous surgery
  • Malignancy with the past 3 years, other than primary MF, post ET MF, or post PV MF. The following history or concurrent conditions are allowed: basal or squamous cell carcinoma, carcinoma in situ of the cervix or the breast, histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system) A history of completed treatment (medical or surgical) of stage 1-2 cancers may be permitted with prior Sponsor agreement.
  • Stroke, deep vein thrombosis, or pulmonary or arterial embolism within 3 months prior to Screening
  • Known allergic reaction to any study drug excipient
  • A history of anti-drug antibody formation
  • Inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or known to have left ventricular ejection fraction > Hepatitis B or C, or human immunodeficiency virus (HIV) with detectable viral load
  • Uncontrolled fungal, bacterial, or viral infection (ongoing signs/symptoms related to the infection, without improvement despite appropriate treatment)
  • Iron chelation therapy in the 28 days prior to Screening
  • Change in anticoagulant therapy regimen within 8 weeks prior to Screening
  • Peripheral blood myeloblasts ≥10% of WBC differential at most recent evaluation prior to Screening
  • Positive direct antiglobulin test in conjunction with a reactive RBC eluate at Screening
  • Pregnant or lactating
  • Condition or concomitant medication that would confound the ability to interpret study data
  • Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgment of the Investigator or Sponsor, would put the participant at unacceptable risk or otherwise preclude the participant from participating in the study
  • Participation in any other clinical protocol or investigational study that involves administration of experimental therapy and/or therapeutic devices within 30 days prior to Screening
  • Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation from other diseases
  • Peripheral blasts ≥5%
  • Prior treatment with hypomethylating agent or other acute myeloid leukemia (AML)-like combination chemotherapy
  • Hereditary hemochromatosis
  • Hemoglobinopathy or intrinsic RBC defect associated with anemia
  • Total splenectomy
  • Hematopoietic cell transplant within the past 10 years
  • 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
  • Major surgery within 8 weeks prior to Screening or incomplete recovery from any previous surgery
  • Additional criteria will apply.

If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.