A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV)

A Phase 2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of DISC-3405 in Participants With Polycythemia Vera (PV)

This open-label, multicenter, within-participant dose escalation study examining up to 2 dose levels of DISC-3405 will assess the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of DISC-3405 in participants with polycythemia vera (PV).

Study Overview

• Status: Recruiting
• Conditions: Polycythemia Vera (PV)
• Intervention / Treatment: Drug: DISC-3405

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Disc Medicine Clinical Trials; Phone Number: (617) 674 9274; Email: clinicaltrials@discmedicine.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic in Arizona
      • Principal Investigator: Jeanne Palmer, M.D.
      • Contact: Eden Knight; Phone Number: 480-342-2000; Email: knight.eden@mayo.edu
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
      • Contact: Christine Duran; Phone Number: 323-865-3000; Email: duran_c@med.usc.edu
      • Contact: Jenny Kim; Phone Number: 323-865-3000; Email: jenny.kim3@med.usc.edu
      • Principal Investigator: Caitlin O'Neill
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Health
      • Principal Investigator: Gary Schiller, M.D.
      • Contact: Bruck Habtemariam; Phone Number: 310-825-5513; Email: bhabtemariam@mednet.ucla.edu
      • Contact: Carla Petro; Phone Number: 310-825-5513; Email: cPetro@mednet.ucla.edu
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Keck Medicine of USC - Cancer Clinic- Newport Beach
      • Principal Investigator: Caitlin O'Neill
      • Contact: Kristy, Massopust; Phone Number: 323-865-3000; Email: massopust_k@med.usc.edu
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida
      • Principal Investigator: Candido Rivera, M.D.
      • Contact: Jordan Oberhaus; Phone Number: 904-953-6523; Email: oberhaus.jordan@mayo.edu
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Minnesota
      • Principal Investigator: Naseema Gangat, M.B.B.S.
      • Contact: Chandra Hutchens; Phone Number: 507-266-4994; Email: hutchens.chandra@mayo.edu
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Siteman Cancer Center - Washington University St. Louis
      • Contact: Nicole Gaudin; Phone Number: 314-362-8814; Email: nrgaudin@wustl.edu
      • Principal Investigator: Stephen Oh
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Atrium Health - Levine Cancer Center
      • Contact: Ashley Franklin; Phone Number: 980-442-4363; Email: Ashley.Franklin@advocatehealth.org
      • Principal Investigator: Anne Wofford
      • Sub-Investigator: Michael Grunwald
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University
      • Contact: Erin Murphy; Phone Number: 919-684-8964; Email: erin.murphy@duke.edu
      • Contact: Caitlyn Campbell; Phone Number: 919-684-8964; Email: caitlyn.campbell@duke.edu
      • Principal Investigator: Lindsay Rein, MD
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Atrium Health Wake Forest Baptist Medical Center
      • Principal Investigator: Anne Wofford
      • Contact: Chelsea Torbush; Phone Number: 336-716-3684; Email: Chelsea.Torbush@Advocatehealth.org
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Aaron Gerds, MD
      • Contact: Alexandrea Thomas; Phone Number: 216-636-1926; Email: thomasa106@ccf.org
      • Contact: Bren Chua; Email: CHUAR@ccf.org
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
      • Contact: Kristen Browning; Phone Number: 540-588-3327; Email: Kristen.Browning@osumc.edu
      • Principal Investigator: Jennifer E Vaughn, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Principal Investigator: Joseph Shatzel
      • Contact: Rachel Mahoney; Phone Number: 513-824-9004; Email: mahoneyr@ohsu.edu
      • Contact: Grace Cheng; Phone Number: 513-824-9004; Email: chengg@ohsu.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Naveen Pemmaraju, M.D.
      • Contact: Nichole Ard; Phone Number: 713-792-4956; Email: NArd@mdanderson.org
      • Contact: Rhona Pinsoy; Phone Number: 713-792-4956; Email: mbpinsoy@mdanderson.org
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington - Fred Hutchinson Cancer Research Center
      • Principal Investigator: Anna Halpern
      • Contact: Cassidy McCarthy; Phone Number: 206-606-6854; Email: cmcca140@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 years or older at the time of signing the informed consent form (ICF).
2. Meet revised 2022 World Health Organization (WHO) criteria for the diagnosis of PV.
3. Complete blood count values at Screening of HCT <45% or HCT <48% if followed by a phlebotomy within 2 weeks, white blood cells 4000/μL to 20,000/μL (inclusive), and platelets 100,000/μL to 1,000,000/μL (inclusive).
4. At least 3 phlebotomies in 26 weeks before Screening or at least 5 phlebotomies in 52 weeks before Screening. At least 1 phlebotomy must be within the 12 weeks prior to Screening.
5. Participants receiving cytoreductive therapy must have been taking for at least 6 months and be on a stable PV therapy regimen for at least 2 months for hydroxyurea, interferon or ruxolitinib with no anticipated need for dose adjustments during the study, or have decreasing dose (with medical monitor approval).
6. Participants treated with phlebotomy alone must have stopped cytoreductive therapy 6 months before Screening.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, or with medical monitor approval, ECOG 2.

8. If male with female sexual partner(s) of childbearing potential, agrees to use one of the following acceptable methods of contraception during the study and for at least 120 days after the last study drug dose:

   1. Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom or diaphragm [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) in conjunction with a barrier method (eg, condom [male or female] or diaphragm)
   4. Confirmed successful vasectomy in conjunction with a barrier method (eg, condom [male or female] or diaphragm)

9. If female, then EITHER postmenopausal, defined as at least 12 months of natural, spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone >40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy with or without hysterectomy); surgically sterile, OR agreeable to use of highly effective contraception (listed below) on Day 1 (or earlier) and for at least 120 days after the last dose of study drug:

   1. Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom [male or female] or diaphragm)
   2. Intrauterine device in place for at least 3 months
   3. Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom [male or female] or diaphragm)
10. Negative pregnancy test (females of childbearing potential).
11. Able to understand the study aims, procedures, and requirements, and provide written informed consent.
12. Able to comply with all study procedures.

Exclusion Criteria:

1. Clinically significant laboratory abnormalities at Screening.
2. Participants who require phlebotomy at HCT levels <45%.
3. Clinically significant thrombosis (eg, deep vein thrombosis or splenic vein thrombosis) within 2 months prior to study treatment.
4. Clinically significant active or chronic bleeding, considered meaningful in consultation with the medical monitor, within 6 months prior to study treatment.
5. Significant renal dysfunction, evidenced by estimated glomerular filtration rate of <30 mL/min/1.73 m2 at the Screening visit, as assessed locally.
6. History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer, or other malignancies deemed acceptable by the Sponsor.
7. Participants with in situ or stage 1 squamous cell carcinoma of the skin, in situ or stage 1 basal cell carcinoma of the skin, or in situ melanoma of the skin identified during Screening unless the cancer is adequately treated before study entry.
8. Received busulfan, pipobroman, or phosphorus-32 within 7 months prior to Screening.
9. Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
10. A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug.
11. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
12. Active human immunodeficiency virus (HIV), hepatitis B or C. A positive hepatitis or HIV result should be discussed between the Investigator and Sponsor prior to enrollment.
13. 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.
14. Condition or concomitant medication that would confound the ability to interpret clinical data, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months.
15. If female, pregnant or breastfeeding.
16. Participation in any other clinical protocol or investigational study that involves administration of experimental therapy and/or therapeutic devices within 30 days (or 5 half-lives for drugs, whichever is longer) of Screening. Previous use of other hepcidin inducing agents that may impact TMPRSS6 expression are not allowed. Previous use of hepcidin mimetics may be allowed in discussion with the Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Within-participant dose escalation; This is an open-label, multicenter, within-participant dose escalation study examining up to 2 dose levels of DISC-3405.	Drug: DISC-3405; DISC-3405 is administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE	Proportion of participants with treatment-emergent adverse events	Up to 365 days
Incidence of clinically abnormal vital signs	Proportion of participants with changes in vital signs	Up to 365 days
Incidence of clinically abnormal physical exam	Proportion of participants with changes in physical examinations	Up to 365 days
Incidence of clinically abnormal electrocardiograms	Proportion of participants with changes in electrocardiograms (ECGs)	Up to 365 days
Incidence of abnormal laboratory test results	Proportion of participants with changes in clinical laboratory results	Up to 365 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants achieving therapeutic response, defined as absence of phlebotomy eligibility, during the maintenance period	Up to 365 days
Number of phlebotomies during the maintenance and optimization periods	Up to 365 days
Proportion of participants achieving therapeutic response, defined as absence of phlebotomy eligibility, during the optimization period	Up to 365 days
Proportion of participants with HCT values <45% throughout the study	Up to 365 days
Area under the plasma concentration versus time curve (AUC) following the first dose	Up to 365 days
Peak plasma concentration (Cmax) following the first dose	Up to 365 days
Elimination half-life (t½el) following the first dose	Up to 365 days
Apparent clearance (CL/F) following the first dose	Up to 365 days
Maximum concentration at steady state (Cmax_ss) after repeating doses	Up to 365 days
Pre-dose trough concentration (Ctrough) after repeating doses	Up to 365 days
Change from baseline for HCT	Up to 365 days
Change from baseline for serum hepcidin-25	Up to 365 days
Change from baseline for serum iron	Up to 365 days
Apparent volume of distribution (Vd/F)	Up to 365 days

Collaborators and Investigators

• Sponsor: Disc Medicine, Inc
• Investigators: Study Director: Will Savage, MD PhD, Disc Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: May 7, 2025
• First Submitted That Met QC Criteria: May 14, 2025
• First Posted (Actual): May 22, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Hemic and Lymphatic Diseases; Polycythemia Vera
• Other Study ID Numbers: DISC-3405-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No