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: 28

Brief Summary

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.

Conditions

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

Keywords

Myeloproliferative Neoplasm; Myeloproliferative Disorders

Outcome Measures

Primary Outcomes (9)

• Safety and Tolerability of DISC-0974 (Phase 1b only)

  Assessed by treatment-emergent adverse events

  From Day 1 to the end of treatment on Day 169

• 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)

  From Day 1 to the end of treatment on Day 169

• Safety and Tolerability of DISC-0974 (Phase 1b only)

  Assessed by physical examinations

  From Day 1 to the end of treatment on Day 169

• 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)

  From Day 1 to the end of treatment on Day 169

• Safety and Tolerability of DISC-0974 assessed through blood testing (Phase 1b only)

  The blood testing will include a hematology panel, blood chemistry panel, serology/virology panel, biomarker assessments, PK assessments, and Anti-Drug Antibodies

  From Day 1 to the end of treatment on Day 169

• Safety and Tolerability of DISC-0974 assessed through urine testing (Phase 1b only)

  The urine testing will include a urinalysis

  From Day 1 to the end of treatment on Day 169

• Transfusion-dependent (TD) high cohort: transfusion independence (Phase 2 only)

  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. Participants meeting this criterion will be considered to have a major response to treatment.

  From Day 1 to the end of treatment on Day 169

• TD low cohort: transfusion independence (Phase 2 only)

  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. Participants meeting this criterion will be considered to have a major response to treatment.

  From Day 1 to the end of treatment on Day 169

• Non-transfusion-dependent (nTD) cohort: anemia response (Phase 2 only)

  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. Participants meeting this criterion will be considered to have a major response to treatment.

  From Day 1 to the end of treatment on Day 169

Secondary Outcomes (46)

• Anemia response defined per IWG-MRT 2006 criteria (Phase 1b only)

  From Day 1 to the end of treatment on Day 169

• 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)

  From Day 1 to the end of treatment on Day 169

• 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)

  From Day 1 to the end of treatment on Day 169

• 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)

  From Day 1 to the end of treatment on Day 169

• nTD participants will be evaluated for ≥1.5 g/dL increase from baseline Hgb levels during the treatment period (Phase 1b only)

  From Day 1 to the end of treatment on Day 169

Other Outcomes (3)

• Cmax (Phase 1b, 2, and Exploratory Cohorts)

  From Day 1 to the end of treatment on Day 169

• Tmax (Phase 1b, 2, and Exploratory Cohorts)

  From Day 1 to the end of treatment on Day 169

• AUC (Phase 1b, 2, and Exploratory Cohorts)

  From Day 0 to 29 days after the first dose

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: 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.
• 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. 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 within the past 3 years, other than primary MF, post ET, or post PV MF. The following history or concurrent conditions are allowed:
• basal or squamous cell carcinoma of the skin
• 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 (28)

Banner MD Anderson

Gilbert, Arizona, 85234, United States

RECRUITING

City of Hope - Duarte

Duarte, California, 91010, United States

RECRUITING

City of Hope - Lennar

Irvine, California, 92618, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, 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

Montefiore

New York, New York, 10467, 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): May 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 20, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (25); AU (3)