DISC-3405 for Polycythemia Vera

Recruiting at 6 trial locations

Overseen By Disc Medicine Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Disc Medicine, Inc

Must be taking: Hydroxyurea, Interferon, Ruxolitinib

Must not be taking: Busulfan, Pipobroman, Phosphorus-32

Disqualifiers: Thrombosis, Bleeding, Renal dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called DISC-3405 for individuals with polycythemia vera (PV), a condition where the body produces too many red blood cells, causing fatigue and headaches. The study aims to assess the treatment's safety, effectiveness, and behavior in the body. Individuals with long-standing PV who require frequent blood draws (phlebotomies) to manage their condition might be suitable candidates. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

If you're on cytoreductive therapy like hydroxyurea, interferon, or ruxolitinib, you need to have been on a stable dose for at least 2 months before the study and should not need dose changes during the trial. If you're only using phlebotomy, you must have stopped other cytoreductive therapies 6 months before the trial.

Is there any evidence suggesting that DISC-3405 is likely to be safe for humans?

Research has shown that DISC-3405 has been tested primarily in healthy individuals. Early results from these studies suggest that DISC-3405 is generally safe and well-tolerated, with no serious side effects reported. This is promising for those considering joining the trial.

The treatment increases a protein called hepcidin, which helps control iron levels in the body. Animal tests have shown positive results. However, this trial will further assess the safety of DISC-3405 in people with polycythemia vera, a condition where the body produces too many red blood cells.

While the early data is encouraging, the current trial aims to determine the right dose and confirm safety for this specific condition. Participants should discuss potential risks with their healthcare providers before enrolling. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for polycythemia vera?

Unlike standard treatments for polycythemia vera, which often include phlebotomy, hydroxyurea, or interferon therapy, DISC-3405 offers a different approach. This investigational drug is exciting because it involves a within-participant dose escalation, allowing researchers to fine-tune the dosage for optimal effectiveness and minimal side effects. Additionally, DISC-3405 may target the disease more precisely, potentially offering better disease management compared to traditional options. Researchers are hopeful that this could lead to improved outcomes and quality of life for patients with polycythemia vera.

What evidence suggests that DISC-3405 might be an effective treatment for polycythemia vera?

Research has shown that DISC-3405 might help treat polycythemia vera, a condition characterized by excessive red blood cell production. Early results indicate that DISC-3405 can significantly reduce iron absorption, with a 94% decrease by Day 2 and 68% by Day 15, thereby lowering iron levels in the body. In early studies, DISC-3405 also increased the production of hepcidin, a hormone that regulates iron levels, and proved effective in disease models. These findings suggest that DISC-3405 has strong potential to manage polycythemia vera by controlling iron levels. ^{1 3 6 7 8}

Who Is on the Research Team?

Will Savage, MD PhD

Principal Investigator

Disc Medicine

Are You a Good Fit for This Trial?

This trial is for people with Polycythemia Vera (PV) who meet the 2022 WHO criteria for PV diagnosis. They should have specific blood count levels, a history of phlebotomies, and may be on stable PV treatments like hydroxyurea or ruxolitinib without dose changes expected during the study. Participants must not need cytoreductive therapy recently and should be in good enough health to perform daily activities.

Inclusion Criteria

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo within-participant dose escalation of DISC-3405 to assess safety, tolerability, and efficacy

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 365 days

What Are the Treatments Tested in This Trial?

Interventions

• DISC-3405

Trial Overview The trial tests DISC-3405's safety and effectiveness in treating PV at up to two different doses. It's an open-label study where everyone knows they're getting DISC-3405, and doctors will watch how it works over time while adjusting doses if needed.

How Is the Trial Designed?

Group I: Within-participant dose escalation Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Disc Medicine, Inc

Lead Sponsor

Trials

6

Recruited

580+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06985147

A Phase 2, Open-Label Study of DISC-3405 in Participants ... This open-label, multicenter, within-participant dose escalation study examining up to 2 dose levels of DISC-3405 will assess the safety, tolerability, ...

2. ir.discmedicine.com ir.discmedicine.com/news-releases/news-release-details/disc-medicine-presents-positive-clinical-data-updates-across

Disc Medicine Presents Positive Clinical Data Updates ... DISC-3405 resulted in an average 94% reduction in iron absorption at Day 2 and 68% at Day 15. These results confirm the mechanism of DISC-3405 ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1092/529328/Phase-1-Healthy-Volunteer-Study-of-DISC-3405-a

Phase 1 Healthy Volunteer Study of DISC-3405, a ... In preclinical studies, DISC-3405 significantly increased hepcidin production, suppressed iron levels, and demonstrated efficacy in disease ...

4. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)02136-6/fulltext

Single- and Multiple-Ascending Doses of DISC-3405, a ... In preclinical studies, DISC-3405 significantly increased hepcidin production, suppressed iron levels, and demonstrated efficacy in disease models of ...

5. firstwordpharma.com firstwordpharma.com/story/6515326

Disc Medicine Announces Presentation of Initial Data from ... We expect to share an initial readout for this trial, as well as for the Phase 1b trial of DISC-3405 in sickle cell disease, in 2026.”.

6. ir.discmedicine.com ir.discmedicine.com/news-releases/news-release-details/disc-medicine-initiates-phase-1-study-disc-3405-anti-tmprss6-mab

Disc Medicine Initiates a Phase 1 Study of DISC-3405 (anti ... Preclinical studies of DISC-3405 have demonstrated an increase in hepcidin production and suppression of serum iron levels in animal models of ...

7. duke-research.dukehealth.org duke-research.dukehealth.org/studies/pro00118054

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics ... We are doing this study to find the most effective, safe dose of an experimental drug called DISC-3405 (the study drug) in adults with polycythemia vera (PV).

8. thalassaemia.org.cy thalassaemia.org.cy/clinical-trial-updates/mwtx-003/

MWTX-003 – TIF DISC-3405, an anti-TMPRSS6 antibody, is designed to increase the production of hepcidin to therapeutically reduce iron.