Myelofibrosis; AnemiaPhase 1/2NCT05320198
Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia
A Phase 1/2 study testing DISC-0974 in people with Myelofibrosis; Anemia and Anemia, run by Disc Medicine, Inc at 35 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis; Anemia, Anemia, Myelofibrosis
- What is being tested?
- DISC-0974
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 35 sitesin 2 countries
- Study dates
- 6 Jun 2022to Jun 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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:
- 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
- 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 <75% (local lab acceptable) at or within 2 weeks of Screening.
- 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.
- Serum ferritin ≥50 µg/L at Screening.
- 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.
- 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 <3.0x upper limit of normal (ULN) at Screening.
- 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.
- 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:
- Stable hormonal contraceptive (≥3 months; female partner)
- Intrauterine device in place for at least 3 months (female partner)
- Surgically sterile hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner)
- Confirmed successful vasectomy
- 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:
- Stable hormonal contraceptive (≥3 months)
- Intrauterine device in place for at least 3 months
- Tubal ligation or single male partner with vasectomy
- Negative urine pregnancy test (females of childbearing potential) at Screening (Days 28 to 2).
- Able to understand the study aims, procedures, and requirements, and provide written informed consent.
- 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:
- Age 18 years or older at the time of signing the ICF.
- 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.
- Washout of at least 28 days is required for prior anemia/neutropenia-directed therapies, including:
- Androgens
- EPO-stimulating agents
- Luspatercept
- Sotatercept (ACE-011)
- Imetelstat
- Granulocyte colony-stimulating factor (G CSF) OR granulocyte-macrophage CSF (GM CSF).
- 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.
- Anemia:
- 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
- Medical history of ≤24 units of PRBC for MDS and anemia
- ECOG performance score ≤2
- Infusion of hematopoietic stem cell transplant not anticipated within 8 months after Screening
- TSAT <75% (local lab acceptable) at or within 2 weeks of Screening
- Liver iron concentration by MRI <7 mg/g dry weight within 3 months of eligibility confirmation by central review
- Serum ferritin ≥50 μg/L at Screening
- Platelet count ≥25,000/μL and <1,000,000/μL, and total WBC count <50,000/μL at Screening or otherwise approved by Sponsor.
- eGFR ≥30 mL/min/1.73 m2 by the CKD-EPI formula
- AST and ALT <3x ULN at Screening
- Direct bilirubin <2x ULN at Screening. Higher levels are acceptable if these can be attributed by the Investigator to ineffective erythropoiesis.
- 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:
- Stable hormonal contraceptive (≥3 months; female partner)
- Intrauterine device in place for at least 3 months (female partner)
- Surgically sterile hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner)
- Confirmed successful vasectomy
- 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:
- Stable hormonal contraceptive (≥3 months)
- Intrauterine device in place for at least 3 months
- Tubal ligation or single male partner with vasectomy
- Negative urine pregnancy test (females of childbearing potential) at Screening (Days 28 to 2).
- Able to understand the study aims, procedures, and requirements, and provide written informed consent.
- Able to comply with all study procedures.
Who cannot join
- 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
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- 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
- 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 <35%
- 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)
- Treatment History, Participants with MF and Anemia
- Iron chelation therapy in the 28 days prior to Screening
- Change in anticoagulant therapy regimen within 8 weeks prior to Screening
- Laboratory Exclusions, Participants with MF and Anemia
- 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
- Miscellaneous, Participants with MF and Anemia
- 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
- 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
- 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%
- Current treatment with hypomethylating agent or other acute myeloid leukemia (AML)-like combination chemotherapy or planned use within 6 months after Screening
- Prior treatment with >3 anemia-directed therapies (unless otherwise approved by Sponsor) including:
- Luspatercept
- Sotatercept (ACE-011)
- EPO-stimulating agent
- Imetelstat
- 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
- Malignancy within the past 3 years, other than MDS or MDS/MPN without excess blasts. 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 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 6 months prior to Screening
- Known allergic reaction to any study drug excipient
- A history of antidrug antibody formation
- Inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or known to have left ventricular ejection fraction <35%
- Active hepatitis B or C, or HIV with detectable viral load
- 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
- Iron chelation therapy in the 28 days prior to Screening
- Change in anticoagulant therapy regimen within 8 weeks prior to Screening
- Laboratory Exclusions, Participants with MDS and Anemia
- Positive direct antiglobulin test in conjunction with a reactive RBC eluate at Screening
- Miscellaneous, Participants with MDS and Anemia
- 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
Trial locations and contacts
35 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
35 sites in 2 countries
United States31 sites, 29 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Linda Kemp, 734-232-4312, lfarhat@med.umich.edu
Moshe Talpaz, MD
- Recruiting
Emory Winship Cancer Institute
Atlanta, Georgia, 30322
Karin Chappelle, karin.chappelle@emory.edu
Danielle Oliver, danielle.oliver@emory.edu
- Recruiting
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Jasmine Cousins, 3037244741, jasmine.cousins@cuanschutz.edu
Brandon McMahon, MD
- Terminated
Gabrail Cancer Center Research
Canton, Ohio, 44718
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Sharon Sanders, 216 448-4478, sanders2@ccf.org
Sunny Dickerson, dickers3@ccf.org
- Recruiting
The Ohio State University
Columbus, Ohio, 43201
Tyler Srail, 6143660233, tyler.srail@osumc.edu
Kristen Browning, 6143660233, kristen.browning@osumc.edu
- Recruiting
City of Hope - Duarte
Duarte, California, 91010
Samantha Humpal, shumpal@coh.org
Shama Hussain, shhussain@coh.org
- Recruiting
START New Jersey
East Brunswick, New Jersey, 08816
Nimisha Pant, Nimisha.Pant@startresearch.com
Bruno Fang, MD
- Withdrawn
Sargon Research - Pennsylvania Cancer Specialists and Research Center
Gettysburg, Pennsylvania, 17325
- Recruiting
Banner MD Anderson
Gilbert, Arizona, 85234
Stephanie Kimmel, 4802565463, stephanie.kimmel@bannerhealth.org
Mark Faber, DO
- Recruiting
MD Anderson
Houston, Texas, 77030
Kurt Schreoder, 346 725 5139, kdschroe@mdanderson.org
Prithviraj Bose, MD
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
Erin Jacobsen, 319-467-5829, erin-frimml@uiowa.edu
Meredith Schaffner, DO
- Recruiting
City of Hope - Lennar
Irvine, California, 92618
Grace Bae, gbae@coh.org
Dina Hassan, dhassan@coh.org
- Recruiting
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Latesha Jones, 904 953 4564, jones.latesha@mayo.edu
James Foran, MD
- Recruiting
UCLA
Los Angeles, California, 90095
Bruce Habtemariam, 3107940242, bhabtemariam@mednet.ucla.edu
Marisa Koda, 3107940242, mkoda@mednet.ucla.edu
- Recruiting
Taylor Cancer Research Center
Maumee, Ohio, 43537
Nadine Nemunaitis, 567-402-4501, NNEMUNAITIS@TCRCPT.ORG
Jennifer Martinez, JMARTINEZ@TCRCPT.ORG
- Recruiting
Sylvester Cancer Center - U Miami
Miami, Florida, 33136
Israel Zagales, israelz@med.miami.edu
Jennifer Posada, jxp2320@med.miami.edu
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Kristin Komnick, 414-805-5276, kkomnick@mcw.edu
Laura Michaelis, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Samantha Mcfadden, 612-360-1081, macfads@mskcc.org
Naa-Akomaah Yeboah, 612-360-1081, yeboahn1@mskcc.org
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
MPD Research Team at Mount Sinai, 212-241-3417, ResearchMPD@mssm.edu
Gabriela Bello, gabriela.bello@mssm.edu
- Recruiting
Montefiore
New York, New York, 10467
Joty Rashid, 7189206310, jorashid@montefiore.org
Olivia Orellano, 718-920-6310, oorellano@montefiore.org
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Greenwood, 267-854-6712, thomas.greenwood@pennmedicine.upenn.edu
Elizabeth Hexner, MD
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Keshara Bandara, bandara@ohsu.edu
Ronan Swords, MD, PhD
- Recruiting
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Chandra Hutchens, hutchens.chandra@mayo.edu
Naseema Gangat, MBBS
- Recruiting
Northwest Oncology
Rolling Meadows, Illinois, 60008
Nowsheen Azeemuddin, nowsheena@northwestoncology.com
Bruce Bank, MD
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Raisa Syed, raisa.syed@ucsf.edu
Eli Vasen, eli.vasen@ucsf.edu
- Recruiting
University of Washington
Seattle, Washington, 98109
Cassidy McCarthy, 206 602 1172, cmcca140@fredhutch.org
Anna Halpern, MD
- Recruiting
Washington University St.Louis
St Louis, Missouri, 63110
Nicole Gaudin, nrgaudin@wustl.edu
Amy Zhou, MD
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Paul Ciero, paul.ciero@moffitt.org
Andrew Kuykendall, MD
- Recruiting
Baylor Scott & White
Temple, Texas, 76508
Lorie Fares, 254-724-1291, lorie.fares@bswhealth.org
Mary Watson, 254-724-1291, maryfrances.watson@bswhealth.org
- Recruiting
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
Libyadda Mosley, limosley@wakehealth.edu
Anne Wofford, MD
Australia4 sites, 4 recruiting
- Recruiting
Linear Clinical Research
Nedlands, 6009
Vanessa Pang, vpang@linear.org.au
Carla Bertone, cbertone@linear.org.au
- Recruiting
Western Health
Saint Albans, 3021
Maria Hadfield, 61383959168, maria.hafield@wh.org.au
Angela Baugh, 61383959168, angela.baugh@wh.org.au
- Recruiting
St. Vincent's Hospital
Sydney, 2010
Joshua Neish, 61403987403, joshua.neish@svha.org.au
Alyssa Pantalone, alyssa.pantalone@svha.org.au
- Recruiting
Perth Blood Institute
West Perth, 6005
Jarod Horobin, 61892005300, jarod@pbi.org.au
Ross Baker, MBBS, BMedSc, FRACP, FACP
About this study
Official 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
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
- Myelofibrosis; Anemia, Anemia, Myelofibrosis, Myelofibrosis Due to and Following Polycythemia Vera, Primary Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis
- Being tested
- DISC-0974
- Keywords
- Myeloproliferative Neoplasm, Myeloproliferative Disorders
- Medical subject headings
- Primary Myelofibrosis, Anemia, Myelodysplastic Syndromes, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DISC-0974Drug
DISC-0974 is administered subcutaneously.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b: Dose Escalation | Experimental | In the Phase 1b (dose-escalation) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks. Receives: 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. Receives: Drug: DISC-0974 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of DISC-0974 (Phase 1b only)
Assessed by treatment-emergent adverse events
Measured: 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)
Measured: From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 1b only)
Assessed by physical examinations
Measured: 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)
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Proportion of participants with treatment-emergent adverse events
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Pharmacokinetic parameters include DISC-0974 pre-dose concentrations at different visits
Measured: 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)
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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Reticulocyte count (Phase 1b and 2)
Measured: From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Hemoglobin levels (Phase 1b and 2)
Measured: From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Reticulocyte Hemoglobin (CHr) (Phase 1b and 2)
Measured: From Day 1 to the end of treatment on Day 169
Hematologic Parameters assessed through Red Blood Cell Count (Phase 1b and 2)
Measured: 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)
Measured: 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)
Measured: 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)
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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
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
Measured: From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 2 only)
Assessed by treatment-emergent adverse events
Measured: From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 2 only)
Assessed by vital signs through blood pressure (mmHg), heart rate (bpm), respiration rate (breaths/min), and temperature (°C)
Measured: From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 2 only)
Assessed by physical examinations
Measured: From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 (Phase 2 only)
Assessed by electrocardiogram (ECG) parameters: heart rate, PR interval, QRS duration, QRS axis, QT interval, and QTcF interval)
Measured: From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 assessed through blood testing (Phase 2 only)
The blood testing will include a hematology panel, blood chemistry panel, serology/virology panel, biomarker assessments, PK assessments, and Anti-Drug Antibodies
Measured: From Day 1 to the end of treatment on Day 169
Safety and Tolerability of DISC-0974 assessed through urine testing (Phase 2 only)
The urine testing will include a urinalysis
Measured: 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)
Assessed by treatment-emergent adverse events
Measured: 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)
Assessed by vital signs through blood pressure (mmHg), heart rate (bpm), respiration rate (breaths/min), and temperature (°C)
Measured: 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)
Assessed by physical examinations
Measured: 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)
Assessed by electrocardiogram (ECG) parameters: heart rate, PR interval, QRS duration, QRS axis, QT interval, and QTcF interval)
Measured: 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)
The blood testing will include a hematology panel, blood chemistry panel, serology/virology panel, biomarker assessments, PK assessments, and Anti-Drug Antibodies
Measured: 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)
The urine testing will include a urinalysis
Measured: From Day 1 to the end of treatment on Day 169
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2022
- Study start6 Jun 2022
- Primary completionMay 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelofibrosis; AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Disc Medicine, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Will Savage, MD PhD, Study director, Disc Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05320198
- Sponsor's protocol ID
- DISC-0974-102
- Status last verified
- Jun 2026
- First submitted
- 15 Mar 2022
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No