This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of DISC-0974 in Participants With Myelofibrosis and Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05320198
Recruitment Status : Recruiting
First Posted : April 11, 2022
Last Update Posted : February 22, 2024
Sponsor:
Information provided by (Responsible Party):
Disc Medicine, Inc

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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 and anemia.

Condition or disease Intervention/treatment Phase
Myelofibrosis; Anemia Anemia Myelofibrosis Myelofibrosis Due to and Following Polycythemia Vera Primary Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Drug: DISC-0974 Phase 1 Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DISC-0974 in Participants With Myelofibrosis and Anemia
Actual Study Start Date : June 6, 2022
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Phase 1b: Dose Escalation
In the Phase 1b (dose-escalation) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks.
 Drug: DISC-0974
DISC-0974 is administered subcutaneously.
Experimental: Phase 2a: Expansion
In the Phase 2a (expansion) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks.
 Drug: DISC-0974
DISC-0974 is administered subcutaneously.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (Phase 1b only) [ Time Frame: up to 225 days ]
  2. Incidence of clinically abnormal vital signs (Phase 1b only) [ Time Frame: up to 225 days ]
  3. Incidence of clinically abnormal physical exam (Phase 1b only) [ Time Frame: up to 225 days ]
  4. Incidence of clinically abnormal electrocardiograms (Phase 1b only) [ Time Frame: up to 225 days ]
  5. Incidence of abnormal laboratory test results (Phase 1b only) [ Time Frame: up to 225 days ]
  6. Anemia response, defined per IWG-MRT criteria (Phase 2a only) [ Time Frame: up to 225 days ]

Secondary Outcome Measures :
  1. Anemia response defined per IWG-MRT criteria (Phase 1b only) [ Time Frame: up to 225 days ]
  2. Change from baseline in concentration of iron laboratory parameters (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  3. Change from baseline in concentration of hematologic laboratory parameters (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  4. Rate of RBC transfusion per participant month during treatment period (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  5. Transfusion response defined per IWG-MRT criteria (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  6. Mean change in Hgb (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  7. Incidence of treatment-emergent adverse events (Phase 2a only) [ Time Frame: up to 225 days ]
  8. Incidence of clinically abnormal vital signs (Phase 2a only) [ Time Frame: up to 225 days ]
  9. Incidence of clinically abnormal physical exam (Phase 2a only) [ Time Frame: up to 225 days ]
  10. Incidence of clinically abnormal electrocardiogram (Phase 2a only) [ Time Frame: up to 225 days ]
  11. Incidence of abnormal laboratory test results (Phase 2a only) [ Time Frame: up to 225 days ]
  12. Cmax-Maximum drug concentration measured in plasma (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  13. Tmax-Time of maximum drug concentration (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  14. AUC-Area under the drug concentration time curve (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  15. T½ - Elimination half life of the drug (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  16. CL/F-Apparent drug clearance (Phase 1b and 2a) [ Time Frame: up to 225 days ]
  17. Vd/F-Apparent volume of distribution of the drug (Phase 1b and 2a) [ Time Frame: up to 225 days ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 years or older at the time of signing the informed consent (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.
  3. Washout of at least 28 days prior to Screening of the following treatments: androgens, erythropoietin, cladribine, immunomodulators (lenalidomide, thalidomide), interferon alpha-2a or any other MF-directed therapy. 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.
  4. Anemia: For Phase 1b: Hemoglobin (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 packed RBCs (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 2a: 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.
  5. Stable dose of JAK inhibitor (except momelotinib) and/or hydroxyurea, or, if taking any other treatment for MF, stable for at least 28 days prior to Screening. Momelotinib use requires 12 weeks of stable dosing prior to Screening. If subject discontinues JAK inhibitor (including momelotinib) and/or hydroxyurea prior to Screening, a 28-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. Transferrin saturation <75% (local lab acceptable).
  9. Liver iron concentration by MRI < 7 mg/g dry weight within 3 months of eligibility confirmation.
  10. Serum ferritin ≥ 30 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/1.73m2 by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula.
  13. Aspartate aminotransferase (AST) and alanine transaminase (ALT) < 3.0 x 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.

Exclusion Criteria:

Medical History:

  1. Hereditary hemochromatosis
  2. Hemoglobinopathy or intrinsic RBC defect associated with anemia
  3. Total splenectomy
  4. Hematopoietic cell transplant within the past 10 years
  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
    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 6 months prior to Screening
  11. Known allergic reaction to any study drug excipient, or anaphylaxis to any food or drug
  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. Active 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:

  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:

  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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05320198


Contacts
Layout table for location contacts
Contact: Disc Medicine Clinical Trials (617) 674 9274 clinicaltrials@discmedicine.com

Locations
Layout table for location information
United States, Florida
Mayo Clinic Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Tiffany Brown    904-953-4564    brown.tiffany@mayo.edu   
Principal Investigator: James Foran, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Linda Kemp    734-232-4312    lfarhat@med.umich.edu   
Principal Investigator: Moshe Talpaz, MD         
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Ashya Burgress       Burgess.Ashya@mayo.edu   
Principal Investigator: Naseema Gangat, MBBS         
United States, Missouri
Washington University St.Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Nicole Gaudin       nrgaudin@wustl.edu   
Principal Investigator: Amy Zhou, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Jack Martin    612-360-1081    martj19@mskcc.org   
Contact: Michelle Gianvito    612-360-1081    gianvitm@mskcc.org   
Principal Investigator: Prioty Islam, MD, MSc         
United States, North Carolina
Atrium Health Wake Forest Baptist Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Libyadda Mosley       limosley@wakehealth.edu   
Principal Investigator: Anne Wofford, MD         
United States, Ohio
Gabrail Cancer Center Research Active, not recruiting
Canton, Ohio, United States, 44718
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Joe Lucchese    216-448-4478    lucchej2@ccf.org   
Principal Investigator: Aaron Gerds, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Colin Hammons       hammonsc@ohsu.edu   
Contact: Keshara Bandara       bandara@ohsu.edu   
Principal Investigator: Ronan Swords, MD, PhD         
United States, Pennsylvania
Sargon Research - Pennsylvania Cancer Specialists and Research Center Withdrawn
Gettysburg, Pennsylvania, United States, 17325
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Thomas Greenwood    267-854-6712    thomas.greenwood@pennmedicine.upenn.edu   
Principal Investigator: Elizabeth Hexner, MD         
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Romany Gergis    346-725-5139    rgergis@mdanderson.org   
Principal Investigator: Prithviraj Bose, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Kayla Pankey    206-602-1172    kpankey@seattlecca.org   
Principal Investigator: Anna Halpern, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Kristin Komnick    414-805-5276    kkomnick@mcw.edu   
Principal Investigator: Laura Michaelis, MD         
Sponsors and Collaborators
Disc Medicine, Inc
Investigators
Layout table for investigator information
Study Director: Will Savage, MD PhD Disc Medicine
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Disc Medicine, Inc
ClinicalTrials.gov Identifier: NCT05320198    
Other Study ID Numbers: DISC-0974-102
First Posted: April 11, 2022    Key Record Dates
Last Update Posted: February 22, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Disc Medicine, Inc:
Myeloproliferative Neoplasm
Myeloproliferative Disorders
Additional relevant MeSH terms:
Layout table for MeSH terms
Polycythemia Vera
Anemia
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Hematologic Diseases
Myeloproliferative Disorders
 Bone Marrow Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders