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

NCT06985147 | Recruiting Phase 2 FDA Drug

• 1 other identifier: DISC-3405-201
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 14

Brief 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).

Conditions

Polycythemia Vera (PV)

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (14)

• 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

Study Arms (1)

Within-participant dose escalation

EXPERIMENTAL

This is an open-label, multicenter, within-participant dose escalation study examining up to 2 dose levels of DISC-3405.

Drug: DISC-3405

Interventions

DISC-3405 DRUG

DISC-3405 is administered subcutaneously.

Within-participant dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Disc Medicine, Inc: lead

Study Sites (14)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

UCLA Health

Los Angeles, California, 90095, United States

RECRUITING

Keck Medicine of USC - Cancer Clinic- Newport Beach

Newport Beach, California, 92663, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic in Minnesota

Rochester, Minnesota, 55905, United States

RECRUITING

Siteman Cancer Center - Washington University St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Atrium Health - Levine Cancer Center

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

RECRUITING

Atrium Health Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Washington - Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Polycythemia Vera

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Study Officials

• Will Savage, MD PhD

  Disc Medicine

  STUDY DIRECTOR

Central Study Contacts

Disc Medicine Clinical Trials

CONTACT

(617) 674 9274; clinicaltrials@discmedicine.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to 3 cohorts of participants are planned: * Cohort A will include 20 participants. The first 4 participants enrolled will be administered a starting dose level of Dose A DISC-3405 subcutaneous which will be followed by within-participant dose escalation. Following Safety Review Committee review of the data, an additional 16 participants will be enrolled and administered a starting dose level of Dose B DISC-3405 subcutaneous. * Cohort B will enroll up to 20 participants administered a dose level of Dose B DISC-3405 subcutaneous once every 4 weeks. * Cohort C is optional and will enroll up to 20 participants administered a dose level up to that previously studied of DISC-3405 subcutaneous once every 4 weeks.

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 22, 2025
• Study Start: August 12, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2029
• Last Updated: March 4, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)