RecruitingPhase 2NCT06985147

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)


Sponsor

Disc Medicine, Inc

Enrollment

60 participants

Start Date

Aug 12, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

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).


Eligibility

Min Age: 18 Years

Inclusion Criteria19

  • Aged 18 years or older at the time of signing the informed consent form (ICF).
  • Meet revised 2022 World Health Organization (WHO) criteria for the diagnosis of PV.
  • 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).
  • 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.
  • 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).
  • Participants treated with phlebotomy alone must have stopped cytoreductive therapy 6 months before Screening.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, or with medical monitor approval, ECOG 2.
  • 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:
  • Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom or diaphragm \[female partner\])
  • Intrauterine device in place for at least 3 months (female partner)
  • Surgically sterile hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm)
  • Confirmed successful vasectomy in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm)
  • 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:
  • Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm)
  • Intrauterine device in place for at least 3 months
  • Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm)
  • Negative pregnancy test (females of childbearing potential).
  • Able to understand the study aims, procedures, and requirements, and provide written informed consent.
  • Able to comply with all study procedures.

Exclusion Criteria16

  • Clinically significant laboratory abnormalities at Screening.
  • Participants who require phlebotomy at HCT levels <45%.
  • Clinically significant thrombosis (eg, deep vein thrombosis or splenic vein thrombosis) within 2 months prior to study treatment.
  • Clinically significant active or chronic bleeding, considered meaningful in consultation with the medical monitor, within 6 months prior to study treatment.
  • Significant renal dysfunction, evidenced by estimated glomerular filtration rate of <30 mL/min/1.73 m2 at the Screening visit, as assessed locally.
  • 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.
  • 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.
  • Received busulfan, pipobroman, or phosphorus-32 within 7 months prior to Screening.
  • Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
  • A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug.
  • History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
  • 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.
  • 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.
  • 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.
  • If female, pregnant or breastfeeding.
  • 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.

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Interventions

DRUGDISC-3405

DISC-3405 is administered subcutaneously.


Locations(14)

Mayo Clinic in Arizona

Phoenix, Arizona, United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

UCLA Health

Los Angeles, California, United States

Keck Medicine of USC - Cancer Clinic- Newport Beach

Newport Beach, California, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

Mayo Clinic in Minnesota

Rochester, Minnesota, United States

Siteman Cancer Center - Washington University St. Louis

St Louis, Missouri, United States

Atrium Health - Levine Cancer Center

Charlotte, North Carolina, United States

Duke University

Durham, North Carolina, United States

Atrium Health Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Washington - Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

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NCT06985147


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