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Studie av DISC-0974 i deltakere med myelofibrose og anemi

21. oktober 2026 oppdatert av: Disc Medicine, Inc

En fase 1b/2a åpen studie for å evaluere sikkerheten, toleransen, farmakokinetikken og farmakodynamikken til DISC-0974 hos deltakere med myelofibrose og anemi

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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Antatt)

150

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Australia
      • Nedlands, Australia, 6009
      • Saint Albans, Australia, 3021
        • Rekruttering
        • Western Health
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • William Renwick, MBBS
      • Sydney, Australia, 2010
      • West Perth, Australia, 6005
        • Rekruttering
        • Perth Blood Institute
        • Ta kontakt med:
        • Hovedetterforsker:
          • Ross Baker, MBBS, BMedSc, FRACP, FACP
  • Forente stater
    • Arizona
      • Gilbert, Arizona, Forente stater, 85234
        • Rekruttering
        • Banner MD Anderson
        • Ta kontakt med:
        • Hovedetterforsker:
          • Mark Faber, DO
    • California
      • Duarte, California, Forente stater, 91010
        • Rekruttering
        • City of Hope - Duarte
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Idoroenyi Amanam, MD
      • Irvine, California, Forente stater, 92618
        • Rekruttering
        • City of Hope - Lennar
        • Hovedetterforsker:
          • Idoroenyi Amanam, MD
        • Ta kontakt med:
        • Ta kontakt med:
      • Los Angeles, California, Forente stater, 90095
      • San Francisco, California, Forente stater, 94143
        • Rekruttering
        • University of California, San Francisco
        • Hovedetterforsker:
          • Jerry Lee, MD, MS
        • Ta kontakt med:
        • Ta kontakt med:
    • Colorado
      • Aurora, Colorado, Forente stater, 80045
        • Rekruttering
        • University of Colorado Anschutz Medical Campus
        • Ta kontakt med:
        • Hovedetterforsker:
          • Brandon McMahon, MD
    • Florida
      • Jacksonville, Florida, Forente stater, 32224
        • Rekruttering
        • Mayo Clinic Jacksonville
        • Hovedetterforsker:
          • James Foran, MD
        • Ta kontakt med:
      • Miami, Florida, Forente stater, 33136
        • Rekruttering
        • Sylvester Cancer Center - U Miami
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Sangeetha Venugopal, MD, MS
      • Tampa, Florida, Forente stater, 33612
        • Rekruttering
        • Moffitt Cancer Center
        • Hovedetterforsker:
          • Andrew Kuykendall, MD
        • Ta kontakt med:
    • Georgia
      • Atlanta, Georgia, Forente stater, 30322
    • Illinois
      • Rolling Meadows, Illinois, Forente stater, 60008
    • Iowa
      • Iowa City, Iowa, Forente stater, 52242
        • Rekruttering
        • University of Iowa
        • Ta kontakt med:
        • Hovedetterforsker:
          • Meredith Schaffner, DO
    • Michigan
      • Ann Arbor, Michigan, Forente stater, 48109
        • Rekruttering
        • University of Michigan
        • Ta kontakt med:
        • Hovedetterforsker:
          • Moshe Talpaz, MD
    • Minnesota
      • Rochester, Minnesota, Forente stater, 55905
        • Rekruttering
        • Mayo Clinic Rochester
        • Hovedetterforsker:
          • Naseema Gangat, MBBS
        • Ta kontakt med:
    • Missouri
      • St Louis, Missouri, Forente stater, 63110
        • Rekruttering
        • Washington University St.Louis
        • Ta kontakt med:
        • Hovedetterforsker:
          • Amy Zhou, MD
    • New Jersey
      • East Brunswick, New Jersey, Forente stater, 08816
    • New York
      • New York, New York, Forente stater, 10029
        • Rekruttering
        • Icahn School of Medicine at Mount Sinai
        • Hovedetterforsker:
          • John Mascarenhas, MD
        • Ta kontakt med:
        • Ta kontakt med:
      • New York, New York, Forente stater, 10021
        • Rekruttering
        • Memorial Sloan Kettering Cancer Center
        • Hovedetterforsker:
          • Prioty Islam, MD, MSc
        • Ta kontakt med:
        • Ta kontakt med:
      • New York, New York, Forente stater, 10467
        • Rekruttering
        • Montefiore
        • Hovedetterforsker:
          • Swati Goel, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • North Carolina
      • Winston-Salem, North Carolina, Forente stater, 27157
        • Rekruttering
        • Atrium Health Wake Forest Baptist
        • Ta kontakt med:
        • Hovedetterforsker:
          • Anne Wofford, MD
    • Ohio
      • Canton, Ohio, Forente stater, 44718
        • Avsluttet
        • Gabrail Cancer Center Research
      • Cleveland, Ohio, Forente stater, 44195
        • Rekruttering
        • Cleveland Clinic
        • Hovedetterforsker:
          • Aaron Gerds, MD
        • Ta kontakt med:
        • Ta kontakt med:
      • Columbus, Ohio, Forente stater, 43201
        • Rekruttering
        • The Ohio State University
        • Hovedetterforsker:
          • Shivani Handa, MD
        • Ta kontakt med:
        • Ta kontakt med:
      • Maumee, Ohio, Forente stater, 43537
        • Rekruttering
        • Taylor Cancer Research Center
        • Hovedetterforsker:
          • John Nemunaitis, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • Oregon
      • Portland, Oregon, Forente stater, 97239
        • Rekruttering
        • Oregon Health and Science University
        • Ta kontakt med:
        • Hovedetterforsker:
          • Ronan Swords, MD, PhD
    • Pennsylvania
      • Gettysburg, Pennsylvania, Forente stater, 17325
        • Tilbaketrukket
        • Sargon Research - Pennsylvania Cancer Specialists and Research Center
      • Philadelphia, Pennsylvania, Forente stater, 19104
    • Texas
      • Houston, Texas, Forente stater, 77030
        • Rekruttering
        • MD Anderson
        • Hovedetterforsker:
          • Prithviraj Bose, MD
        • Ta kontakt med:
      • Temple, Texas, Forente stater, 76508
    • Washington
      • Seattle, Washington, Forente stater, 98109
        • Rekruttering
        • University of Washington
        • Hovedetterforsker:
          • Anna Halpern, MD
        • Ta kontakt med:
    • Wisconsin
      • Milwaukee, Wisconsin, Forente stater, 53226
        • Rekruttering
        • Medical College of Wisconsin
        • Hovedetterforsker:
          • Laura Michaelis, MD
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria for Participants with MF and Anemia:

Participants are eligible for the study if all of the following criteria apply:

  1. Age 18 years or older at the time of signing the informed consent form (ICF).

  2. 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.

  3. Washout of at least 28 days prior to Screening of the following treatments:

    1. Androgens
    2. EPO
    3. Cladribine
    4. Immunomodulators (lenalidomide, thalidomide)
    5. Luspatercept/sotatercept
    6. 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.

  4. 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:

    TD high transfusion burden cohort: RBC transfusion dependence, defined as an RBC transfusion requirement of 3 to 12 PRBC units over the 84 days immediately prior to Screening TD low transfusion burden cohort: RBC transfusion dependence, defined as an RBC transfusion requirement of 1 to 2 PRBC units over the 84 days immediately prior to Screening nTD Cohort: Non-transfusion dependence, baseline Hgb <10 g/dL as defined on ≥3 assessments over 84 days prior to Screening, without RBC transfusion

  5. Stable dosing of MF-directed therapy:

    1. Hydroxyurea, or, if taking any other treatment for MF, stable for at least 28 days prior to Screening.
    2. Interferon alpha stable dosing for at least 12 weeks prior to Screening.
    3. 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.
    4. If the participant discontinues JAK inhibitor (including momelotinib/pacritinib/ruxolitinib/fedratinib) and/or hydroxyurea prior to Screening, a 60-day washout period is required.

  6. Eastern Cooperative Oncology Group (ECOG) performance score ≤2.

  7. Infusion of hematopoietic stem cell transplant not anticipated within 8 months after Screening.

  8. TSAT <75% (local lab acceptable) at or within 2 weeks of Screening.

  9. Liver iron concentration by MRI <7 mg/g dry weight within 3 months of eligibility confirmation by central review. Required for TD high participants only.

  10. Serum ferritin ≥50 µg/L at Screening.

  11. Platelet count ≥25,000/µL and <1,000,000/µL; neutrophils ≥1,000/µL; and total white blood cell (WBC) count <50,000/µL at Screening.

  12. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula.

  13. Aspartate aminotransferase (AST) and ALT <3.0x upper limit of normal (ULN) at Screening.

  14. Direct bilirubin <2x ULN at Screening. Higher levels are acceptable if these can be attributed by the Investigator to ineffective erythropoiesis or Gilbert's syndrome, with approval from Sponsor.

  15. If male with female sexual partner(s) of childbearing potential, agrees to use 1 of the following highly effective methods of contraception during the study and for at least 8 weeks after the last study drug dose:

    1. Stable hormonal contraceptive (≥3 months; female partner)
    2. Intrauterine device in place for at least 3 months (female partner)
    3. Surgically sterile hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner)
    4. Confirmed successful vasectomy

  16. If female, then EITHER postmenopausal (defined as 12 months of spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels >40 mIU/ml, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy), surgically sterile, OR agreeable to use 1 of the following highly effective contraception methods (listed below) on Day 1 (or earlier) and for at least 8 weeks after the last dose of study drug:

    1. Stable hormonal contraceptive (≥3 months)
    2. Intrauterine device in place for at least 3 months
    3. Tubal ligation or single male partner with vasectomy

  17. Negative urine pregnancy test (females of childbearing potential) at Screening (Days 28 to 2).

  18. Able to understand the study aims, procedures, and requirements, and provide written informed consent.

  19. Able to comply with all study procedures.

Inclusion Criteria for Exploratory Cohort of Participants with MDS and Anemia:

Participants are eligible for the MDS exploratory cohort if all of the following criteria apply:

  1. Age 18 years or older at the time of signing the ICF.

  2. Molecular International Prognostic Scoring System (IPSS-M) classification of very low, low, or intermediate (ie, lower risk) MDS-ringed sideroblasts (RS) negative, MDS/MPN with ringed sideroblasts and thrombocytosis (RS-T), Chronic Myelomonocytic Leukemia (CMML), Atypical Chronic Myeloid Leukemia (aCML), or Myelodysplastic/Myeloproliferative Neoplasms, Unclassifiable (MDS/MPN-U) as confirmed in the most recent local bone marrow biopsy report according to WHO criteria.

  3. Washout of at least 28 days is required for prior anemia/neutropenia-directed therapies, including:

    1. Androgens
    2. EPO-stimulating agents
    3. Luspatercept
    4. Sotatercept (ACE-011)
    5. Imetelstat
    6. Granulocyte colony-stimulating factor (G CSF) OR granulocyte-macrophage CSF (GM CSF).
    7. Systemic corticosteroids (except for participants on a stable or decreasing dose for ≥28 days prior to randomization for non-hematological conditions 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.

  4. Anemia:

    1. Baseline Hgb of <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 during the 84 days prior to Screening
    2. Medical history of ≤24 units of PRBC for MDS and anemia

  5. ECOG performance score ≤2

  6. Infusion of hematopoietic stem cell transplant not anticipated within 8 months after Screening

  7. TSAT <75% (local lab acceptable) at or within 2 weeks of Screening

  8. Liver iron concentration by MRI <7 mg/g dry weight within 3 months of eligibility confirmation by central review

  9. Serum ferritin ≥50 μg/L at Screening

  10. Platelet count ≥25,000/μL and <1,000,000/μL, and total WBC count <50,000/μL at Screening or otherwise approved by Sponsor.

  11. eGFR ≥30 mL/min/1.73 m2 by the CKD-EPI formula

  12. AST and ALT <3x ULN at Screening

  13. Direct bilirubin <2x ULN at Screening. Higher levels are acceptable if these can be attributed by the Investigator to ineffective erythropoiesis.

  14. If male with female sexual partner(s) of childbearing potential, agrees to use 1 of the following highly effective methods of contraception during the study and for at least 8 weeks after the last study drug dose:

    1. Stable hormonal contraceptive (≥3 months; female partner)
    2. Intrauterine device in place for at least 3 months (female partner)
    3. Surgically sterile hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner)
    4. Confirmed successful vasectomy

  15. If female, then EITHER postmenopausal (defined as 12 months of spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/ml, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy), surgically sterile, OR agreeable to use 1 of the following highly effective contraception methods (listed below) on Day 1 (or earlier) and for at least 8 weeks after the last dose of study drug:

    1. Stable hormonal contraceptive (≥3 months)
    2. Intrauterine device in place for at least 3 months
    3. Tubal ligation or single male partner with vasectomy

  16. Negative urine pregnancy test (females of childbearing potential) at Screening (Days 28 to 2).

  17. Able to understand the study aims, procedures, and requirements, and provide written informed consent.

  18. Able to comply with all study procedures.

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

  1. Hereditary hemochromatosis

  2. Hemoglobinopathy or intrinsic RBC defect associated with anemia

  3. Total splenectomy

  4. Hematopoietic cell transplant within the past 2 years, or graft vs host disease requiring immunosuppression

  5. Current anemia from iron deficiency, vitamin B12 or folate deficiency, infection, or bleeding

  6. Active immune-mediated hemolytic anemia

  7. 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

  8. Major surgery within 8 weeks prior to Screening or incomplete recovery from any previous surgery

  9. Malignancy within the past 3 years, other than primary MF, post ET, or post PV MF. The following history or concurrent conditions are allowed:

    1. basal or squamous cell carcinoma of the skin
    2. carcinoma in situ of the cervix or the breast
    3. 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

  10. Stroke, deep vein thrombosis, or pulmonary or arterial embolism within 3 months prior to Screening

  11. Known allergic reaction to any study drug excipient

  12. A history of anti-drug antibody formation

  13. Inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or known to have left ventricular ejection fraction <35%

  14. Hepatitis B or C, or human immunodeficiency virus (HIV) with detectable viral load

  15. Uncontrolled fungal, bacterial, or viral infection (ongoing signs/symptoms related to the infection, without improvement despite appropriate treatment)

    Treatment History, Participants with MF and Anemia

  16. Iron chelation therapy in the 28 days prior to Screening

  17. Change in anticoagulant therapy regimen within 8 weeks prior to Screening

    Laboratory Exclusions, Participants with MF and Anemia

  18. Peripheral blood myeloblasts ≥10% of WBC differential at most recent evaluation prior to Screening

  19. Positive direct antiglobulin test in conjunction with a reactive RBC eluate at Screening

    Miscellaneous, Participants with MF and Anemia

  20. Pregnant or lactating

  21. Condition or concomitant medication that would confound the ability to interpret study data

  22. 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

  23. 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

Exclusion Criteria for Exploratory Cohort of Participants with MDS and Anemia:

Participants are excluded from the MDS exploratory cohort if any of the following criteria apply:

Medical History, Participants with MDS and Anemia

  1. 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

  2. Peripheral blasts ≥5%

  3. Current treatment with hypomethylating agent or other acute myeloid leukemia (AML)-like combination chemotherapy or planned use within 6 months after Screening

  4. Prior treatment with >3 anemia-directed therapies (unless otherwise approved by Sponsor) including:

    1. Luspatercept
    2. Sotatercept (ACE-011)
    3. EPO-stimulating agent
    4. Imetelstat

  5. Hereditary hemochromatosis

  6. Hemoglobinopathy or intrinsic RBC defect associated with anemia

  7. Total splenectomy

  8. Hematopoietic cell transplant within the past 10 years

  9. Current anemia from iron deficiency, vitamin B12 or folate deficiency, infection, or bleeding

  10. Active immune-mediated hemolytic anemia

  11. 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

  12. Major surgery within 8 weeks prior to Screening or incomplete recovery from any previous surgery

  13. Malignancy within the past 3 years, other than MDS or MDS/MPN without excess blasts. The following history or concurrent conditions are allowed:

    1. Basal or squamous cell carcinoma of the skin
    2. Carcinoma in situ of the cervix or the breast
    3. Histologic finding of prostate cancer (T1a or T1b using the TNM clinical staging system) A history of completed treatment (medical or surgical) of stage 1-2 cancers may be permitted with prior Sponsor agreement

  14. Stroke, deep vein thrombosis, or pulmonary or arterial embolism within 6 months prior to Screening

  15. Known allergic reaction to any study drug excipient

  16. A history of antidrug antibody formation

  17. Inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or known to have left ventricular ejection fraction <35%

  18. Active hepatitis B or C, or HIV with detectable viral load

  19. Uncontrolled fungal, bacterial, or viral infection (ongoing signs/symptoms related to the infection, without improvement despite appropriate treatment)

    Treatment History, Participants with MDS and Anemia

  20. Iron chelation therapy in the 28 days prior to Screening

  21. Change in anticoagulant therapy regimen within 8 weeks prior to Screening

    Laboratory Exclusions, Participants with MDS and Anemia

  22. Positive direct antiglobulin test in conjunction with a reactive RBC eluate at Screening

    Miscellaneous, Participants with MDS and Anemia

  23. Pregnant or lactating

  24. Condition or concomitant medication that would confound the ability to interpret study data

  25. 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

  26. 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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Phase 1b: Dose Escalation

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

DISC-0974 is administered subcutaneously.
Eksperimentell: Phase 2: Expansion

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

DISC-0974 is administered subcutaneously.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Safety and Tolerability of DISC-0974 (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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)
Tidsramme: From Day 1 to the end of treatment on Day 169

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)
Tidsramme: From Day 1 to the end of treatment on Day 169

Assessed by physical examinations
From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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)
Tidsramme: From Day 1 to the end of treatment on Day 169

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)
Tidsramme: From Day 1 to the end of treatment on Day 169

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)
Tidsramme: From Day 1 to the end of treatment on Day 169

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)
Tidsramme: From Day 1 to the end of treatment on Day 169

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)
Tidsramme: From Day 1 to the end of treatment on Day 169

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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Incidence of clinically abnormal vital signs following repeated DISC-0974 SC doses in participants with myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) without excess blasts and anemia (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Incidence of clinically abnormal physical exam following repeated DISC-0974 SC doses in participants with myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) without excess blasts and anemia (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Incidence of clinically abnormal electrocardiograms (ECGs) following repeated DISC-0974 SC doses in participants with myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) without excess blasts and anemia (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Incidence of abnormal laboratory test results following repeated DISC-0974 SC doses in participants with myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) without excess blasts and anemia (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
PD markers of mechanism engagement, including exploratory cohorts assessed through serum iron levels (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
PD markers of mechanism engagement, including exploratory cohorts assessed through TSAT levels (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
PD markers of mechanism engagement, including exploratory cohorts assessed through Ferritin levels (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
PD markers of mechanism engagement, including exploratory cohorts assessed through Transferrin levels (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
PD markers of mechanism engagement, including exploratory cohorts assessed through Serum-hepcidin-25 levels (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Reticulocyte count (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Hemoglobin levels (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Reticulocyte Hemoglobin (CHr) (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Red Blood Cell Count (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Rate of RBC transfusions per participant month during the treatment period for each cohort (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
The number of units of RBC transfusions per participant month during the treatment period for each cohort (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Mean change in Hgb over 12-week treatment periods will be evaluated for all cohorts (nTD, TD low, and TD high) (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Maximum duration of RBC-transfusion-independent response for TD participants (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Proportion of participants that require dose escalation in each cohort (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Mean hemoglobin increase of ≥1.5 g/dL over any 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)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
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)
Tidsramme: From Day 1 to the end of treatment on Day 169
From Day 1 to the end of treatment on Day 169
Anemia response defined per IWG-MRT 2006 criteria (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169

Response in nTD participants is defined as ≥2.0 g/dL increase from baseline in Hgb levels. Response in TD participants requires absence of PRBC transfusions during any rolling 12-week period during the treatment period, capped by an Hgb level of ≥8.5 g/dL.
From Day 1 to the end of treatment on Day 169
Incidence of TEAEs following repeated DISC-0974 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)
Tidsramme: From Day 1 to the end of treatment on Day 169

Proportion of participants with treatment-emergent adverse events
From Day 1 to the end of treatment on Day 169
Pharmacokinetic data of DISC-0974 following repeated SC doses in participants with myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) without excess blasts and anemia (Phase 1b only)
Tidsramme: From Day 1 to the end of treatment on Day 169

Pharmacokinetic parameters include DISC-0974 pre-dose concentrations at different visits
From Day 1 to the end of treatment on Day 169
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 PRBC transfusions in each cohort (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169

Participants who are nTD and achieve a mean Hgb increase ≥1 g/dL from baseline over any rolling 12-week period in the absence of transfusion will be considered to have a minor response to treatment.
From Day 1 to the end of treatment on Day 169
Transfusion-dependent cohorts will be evaluated for proportion of participants who reduce their transfusion requirement by ≥50%, as compared to baseline, over any rolling 12-week period during treatment. (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169

Participants who are TD and achieve a reduction in transfusion requirement ≥50% as compared to baseline over any rolling 12-week period during treatment will be considered to have a minor response to treatment.
From Day 1 to the end of treatment on Day 169
Non-transfusion-dependent (nTD) cohort will be evaluated for anemia response (Phase 1b and 2)
Tidsramme: From Day 1 to the end of treatment on Day 169

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
From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

Assessed by treatment-emergent adverse events
From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

Assessed by physical examinations
From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

The urine testing will include a urinalysis
From Day 1 to the end of treatment on Day 169
Safety and tolerability of DISC-0974 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib therapy (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

Assessed by treatment-emergent adverse events
From Day 1 to the end of treatment on Day 169
Safety and tolerability of DISC-0974 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib therapy (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib therapy (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

Assessed by physical examinations
From Day 1 to the end of treatment on Day 169
Safety and tolerability of DISC-0974 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib therapy (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib therapy assessed through blood testing (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

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 following repeated SC doses in participants with MF receiving concomitant momelotinib or pacritinib therapy assessed through urine testing (Phase 2 only)
Tidsramme: From Day 1 to the end of treatment on Day 169

The urine testing will include a urinalysis
From Day 1 to the end of treatment on Day 169

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Cmax (Phase 1b, 2, and Exploratory Cohorts)
Tidsramme: From Day 1 to the end of treatment on Day 169

Maximum drug concentration (observed). Will be determined from blood PK sampling if appropriate data are available
From Day 1 to the end of treatment on Day 169
Tmax (Phase 1b, 2, and Exploratory Cohorts)
Tidsramme: From Day 1 to the end of treatment on Day 169

Observed time of the maximum drug concentration. Will be determined from blood PK sampling if appropriate data are available
From Day 1 to the end of treatment on Day 169
AUC (Phase 1b, 2, and Exploratory Cohorts)
Tidsramme: From Day 0 to 29 days after the first dose

Area under the drug concentration-time curve calculated using linear trapezoidal summation from time zero to 29 days following the first dose. Will be determined from blood PK sampling if appropriate data are available.
From Day 0 to 29 days after the first dose

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Disc Medicine, Inc

Etterforskere

  • Studieleder: Will Savage, MD PhD, Disc Medicine

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

6. juni 2022

Primær fullføring (Antatt)

1. mai 2027

Studiet fullført (Antatt)

1. juni 2027

Datoer for studieregistrering

Først innsendt

15. mars 2022

Først innsendt som oppfylte QC-kriteriene

1. april 2022

Først lagt ut (Faktiske)

11. april 2022

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

22. oktober 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. oktober 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • DISC-0974-102

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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