Study of DISC-0974 in Participants With Myelofibrosis and Anemia

Anemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05320198
• Other study ID #: DISC-0974-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 6, 2022
• Est. completion date: October 2024

Study information

• Verified date: February 2024
• Source: Disc Medicine, Inc
• Contact: Disc Medicine Clinical Trials
• Phone: (617) 674 9274
• Email: clinicaltrials[@]discmedicine.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Myelofibrosis
• Myelofibrosis; Anemia
• Polycythemia
• Polycythemia Vera
• Post-essential Thrombocythemia Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• DISC-0974
DISC-0974 is administered subcutaneously.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Sargon Research - Pennsylvania Cancer Specialists and Research Center	Gettysburg	Pennsylvania
United States	MD Anderson	Houston	Texas
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Washington University St.Louis	Saint Louis	Missouri
United States	University of Washington	Seattle	Washington
United States	Atrium Health Wake Forest Baptist	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Disc Medicine, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (Phase 1b only)		up to 225 days
Primary	Incidence of clinically abnormal vital signs (Phase 1b only)		up to 225 days
Primary	Incidence of clinically abnormal physical exam (Phase 1b only)		up to 225 days
Primary	Incidence of clinically abnormal electrocardiograms (Phase 1b only)		up to 225 days
Primary	Incidence of abnormal laboratory test results (Phase 1b only)		up to 225 days
Primary	Anemia response, defined per IWG-MRT criteria (Phase 2a only)		up to 225 days
Secondary	Anemia response defined per IWG-MRT criteria (Phase 1b only)		up to 225 days
Secondary	Change from baseline in concentration of iron laboratory parameters (Phase 1b and 2a)		up to 225 days
Secondary	Change from baseline in concentration of hematologic laboratory parameters (Phase 1b and 2a)		up to 225 days
Secondary	Rate of RBC transfusion per participant month during treatment period (Phase 1b and 2a)		up to 225 days
Secondary	Transfusion response defined per IWG-MRT criteria (Phase 1b and 2a)		up to 225 days
Secondary	Mean change in Hgb (Phase 1b and 2a)		up to 225 days
Secondary	Incidence of treatment-emergent adverse events (Phase 2a only)		up to 225 days
Secondary	Incidence of clinically abnormal vital signs (Phase 2a only)		up to 225 days
Secondary	Incidence of clinically abnormal physical exam (Phase 2a only)		up to 225 days
Secondary	Incidence of clinically abnormal electrocardiogram (Phase 2a only)		up to 225 days
Secondary	Incidence of abnormal laboratory test results (Phase 2a only)		up to 225 days
Secondary	Cmax-Maximum drug concentration measured in plasma (Phase 1b and 2a)		up to 225 days
Secondary	Tmax-Time of maximum drug concentration (Phase 1b and 2a)		up to 225 days
Secondary	AUC-Area under the drug concentration time curve (Phase 1b and 2a)		up to 225 days
Secondary	T½ - Elimination half life of the drug (Phase 1b and 2a)		up to 225 days
Secondary	CL/F-Apparent drug clearance (Phase 1b and 2a)		up to 225 days
Secondary	Vd/F-Apparent volume of distribution of the drug (Phase 1b and 2a)		up to 225 days