Hepcidin Mimetic for Polycythemia Vera

Recruiting at 16 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Protagonist Therapeutics, Inc.

Must be taking: Cytoreductive therapy

Disqualifiers: Bleeding, Myelofibrosis, Immunodeficiency, 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

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are on cytoreductive therapy with hydroxyurea, interferon, or ruxolitinib, you can continue as long as your dose is stable or decreasing for at least 8 weeks before starting the trial. If you are not on these therapies, you must have stopped any prior cytoreductive therapy at least 24 weeks before joining the trial.

What data supports the effectiveness of the drug PTG-300 for treating polycythemia vera?

Research shows that hepcidin mimetics, like PTG-300, can help control blood cell levels in polycythemia vera by limiting iron availability, which is crucial for red blood cell production. This approach has shown promise in reducing the need for phlebotomy (blood removal) and managing symptoms in patients. ^{1 2 3 4 5}

Is the hepcidin mimetic treatment generally safe for humans?

The hepcidin mimetic, rusfertide, is in late-stage clinical development for treating polycythemia vera, indicating it has undergone significant safety evaluations. Additionally, minihepcidins, similar hepcidin agonists, have shown potential as safe therapeutics in animal models for conditions like β-thalassemia and polycythemia vera, suggesting a favorable safety profile. ^{1 2 4 6 7}

How does the drug PTG-300 differ from other treatments for polycythemia vera?

PTG-300, also known as rusfertide, is unique because it is a hepcidin mimetic that helps control iron levels in the body, offering a noncytoreductive option to manage polycythemia vera without the need for regular blood removal (phlebotomy). This approach targets the hepcidin-ferroportin axis, which is different from traditional treatments that often focus on reducing blood cell production. ^{1 2 7 8 9}

What is the purpose of this trial?

This trial tests PTG-300, a new medication, in patients with polycythemia vera who need regular blood removal. PTG-300 aims to keep red blood cell levels in check, reducing the need for frequent blood removal.

Eligibility Criteria

Adults diagnosed with polycythemia vera, who've had regular phlebotomies for at least 28 weeks and are either on a stable or decreasing dose of cytoreductive therapy (like hydroxyurea, interferon, or ruxolitinib) for over 24 weeks. Those not on such therapies must have stopped them for at least 24 weeks prior.

Inclusion Criteria

You must meet ALL of the following inclusion criteria to be enrolled.

Records of all phlebotomies performed for at least 28 weeks (preferably up to 52 weeks) before dosing are available.

I've been on a stable or decreasing dose of specific blood cancer treatments for at least 8 weeks.

Exclusion Criteria

I have not had any active or chronic bleeding in the last 4 weeks.

I haven't had surgery under general anesthesia in the last month and don't plan any during the study.

I have been diagnosed with myelofibrosis following polycythemia vera.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

28 week dose finding phase to identify a dose that maintains hematocrit <45%

28 weeks

Randomized Withdrawal

12 week randomized withdrawal phase to confirm the response

12 weeks

Open-label Extension

Participants enter an up to 3 year open label extension to investigate long term safety

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PTG-300

Trial Overview The trial is testing PTG-300, a hepcidin mimetic against a placebo in patients requiring frequent blood withdrawals due to polycythemia vera. It includes an initial phase where everyone gets PTG-300 to find the best dose followed by a blind test where neither doctors nor patients know who's getting what.

Participant Groups

Group I: Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3) Experimental Treatment 2 Interventions

Group II: Dose finding PTG-300 (Part 1); PTG-300 (Part 2); Open label extension PTG-300 (Part 3) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Protagonist Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

960+

References

1. United States pubmed.ncbi.nlm.nih.gov

Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Emerging agents and regimens for polycythemia vera and essential thrombocythemia. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Tmprss6-ASO as a tool for the treatment of Polycythemia Vera mice. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Recent advances in prognostication and treatment of polycythemia vera. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Iron homeostasis governs erythroid phenotype in polycythemia vera. [2023]

7. Italy pubmed.ncbi.nlm.nih.gov

Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult β-thalassemia major. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Hepcidin in human iron disorders: therapeutic implications. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Modulation of hepcidin as therapy for primary and secondary iron overload disorders: preclinical models and approaches. [2021]