Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia

NCT05320198 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DISC-0974-102
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 25

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.

Conditions

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

Keywords

Myeloproliferative Neoplasm; Myeloproliferative Disorders

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (31)

• 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

Study Arms (2)

Phase 1b: Dose Escalation

EXPERIMENTAL

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

Drug: DISC-0974

Phase 2: Expansion

EXPERIMENTAL

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

Drug: DISC-0974

Interventions

DISC-0974 DRUG

DISC-0974 is administered subcutaneously.

Phase 1b: Dose Escalation; Phase 2: Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Screening can begin before the 28 day washout is completed, but the washout period must be completed prior to collection of Screening blood samples.
• Anemia:
• For Phase 1b: Hgb \<10 g/dL on ≥3 assessments over 84 days prior to Screening, without RBC transfusion, or Hgb \<10 g/dL and receiving RBC transfusions periodically but not meeting criteria for TD participant as defined for the TD Cohort (see Section 6.3). The baseline Hgb value for these participants is the lowest Hgb level during the 84 days prior to Screening, or RBC transfusion dependence, defined as an RBC transfusion frequency of 6 units PRBC over the 84 days immediately prior to Screening There must not be any consecutive 42 day period without an RBC transfusion in the 84 day period, and the last transfusion must be within 28 days prior to Screening.
• For Phase 2:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Disc Medicine, Inc: lead

Study Sites (25)

City of Hope - Duarte

Duarte, California, 91010, United States

RECRUITING

City of Hope - Lennar

Irvine, California, 92618, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

Sylvester Cancer Center - U Miami

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University St.Louis

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

TERMINATED

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43201, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Sargon Research - Pennsylvania Cancer Specialists and Research Center

Gettysburg, Pennsylvania, 17325, United States

WITHDRAWN

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

University of Washington

Seattle, Washington, 98109, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Linear Clinical Research

Nedlands, 6009, Australia

RECRUITING

St. Vincent's Hospital

Sydney, 2010, Australia

RECRUITING

Perth Blood Institute

West Perth, 6005, Australia

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis; Anemia; Myelodysplastic Syndromes; Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Will Savage, MD PhD

  Disc Medicine

  STUDY DIRECTOR

Central Study Contacts

Disc Medicine Clinical Trials

CONTACT

(617) 674 9274; clinicaltrials@discmedicine.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: April 11, 2022
• Study Start: June 6, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (22); AU (3)