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

Phase 2

Not yet recruiting

• Conditions: Polycythemia Vera (PV)
• Interventions: Drug: DISC-3405

• Registration Number: NCT06985147
• Lead Sponsor: Disc Medicine, Inc

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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-07
• Study First Submitted QC: 2025-05-14
• Last Update Submitted: 2025-05-14
• Study First Posted: 2025-05-22
• Last Update Posted: 2025-05-22
• Study Start: 2025-06
• Primary Completion: 2027-02
• Study Completion: 2029-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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 prior to Day 1 of HCT <45% or HCT <48% if followed by a phlebotomy within 2 weeks prior to baseline, 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 study treatment or at least 5 phlebotomies in 52 weeks before study treatment. 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-alpha 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 and serum follicle-stimulating hormone >40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy or hysterectomy); OR agreeable to use of highly effective contraception (listed below) on Day 1 (or earlier) 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 of Screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
Area under the plasma concentration versus time curve (AUC) following the first dose	Up to 365 days
Proportion of participants achieving therapeutic response, defined as absence of phlebotomy eligibility, during the optimization period	Up to 365 days
Peak plasma concentration (Cmax) following the first dose	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 maintenance period	Up to 365 days
Proportion of participants with HCT values <45% throughout the study	Up to 365 days