Rusfertide for Polycythemia Vera

(THRIVE Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Protagonist Therapeutics, Inc.

Must be taking: Rusfertide

Disqualifiers: Pregnancy, Hypersensitivity, Progressive disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 0-2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term safety and effectiveness of rusfertide for individuals with polycythemia vera, a condition characterized by excessive red blood cell production. It targets those who have used rusfertide for at least a year in a previous study. Participants must have completed that earlier study and be prepared to continue the treatment. The trial aims to assess rusfertide's effectiveness over an extended period and confirm its safety. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to the potential availability of an effective treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use other investigational treatments during the study or within 28 days after the last rusfertide dose.

Is there any evidence suggesting that rusfertide is likely to be safe for humans?

Research has shown that rusfertide is generally well-tolerated by people with polycythemia vera, a blood disorder. One study found that rusfertide significantly reduced the need for blood draws and helped control red blood cell levels, suggesting it can effectively manage symptoms with few side effects.

Patients in earlier studies responded well to rusfertide without major safety concerns. The current trial is in an advanced stage, indicating strong evidence of the treatment's safety for humans. However, researchers continue to monitor for any side effects, as with any treatment. ^{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 involve phlebotomy or medication like hydroxyurea to reduce blood thickness, rusfertide offers a novel approach by directly targeting the hormone that regulates red blood cell production. Researchers are excited about rusfertide because it acts on hepcidin, a key regulator of iron, which is essential for red blood cell production. This mechanism can potentially control blood cell counts more precisely and reduce the need for frequent blood removal or chemotherapy, offering patients a more tailored and less invasive treatment option.

What evidence suggests that rusfertide might be an effective treatment for polycythemia vera?

Research has shown that rusfertide holds promise for treating polycythemia vera, a condition characterized by excessive red blood cell production. In one study, about 77% of patients taking rusfertide improved, compared to only about 33% in the placebo group. This indicates that rusfertide significantly helped control blood levels. Another study found that rusfertide quickly lowered the percentage of red blood cells to safer levels. It also reduced the need for blood removal treatments and improved patients' quality of life. Overall, these results suggest rusfertide effectively manages polycythemia vera. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with Polycythemia Vera who have already been treated with rusfertide for at least 12 months in a previous Phase 2 or Phase 3 study. Participants must understand the study, be willing to follow its rules, and give written consent.

Inclusion Criteria

I completed a year of rusfertide treatment and finished the final visit of a prior study.

I understand the study, can follow its requirements, and agree to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue treatment with rusfertide to assess long-term safety and efficacy

0-2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Open-label rusfertide

Trial Overview The trial is testing the long-term safety and effectiveness of an open-label drug called rusfertide in patients with Polycythemia Vera. It's an extension for those who've completed prior rusfertide studies.

How Is the Trial Designed?

Group I: Open-label rusfertide Experimental Treatment 1 Intervention

Open-label rusfertide

Who Is Running the Clinical Trial?

Protagonist Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

960+

Published Research Related to This Trial

Eltrombopag's bioavailability is significantly reduced (by 59% for AUC and 65% for Cmax) when taken with a high-fat, high-calcium breakfast compared to a fasted state, indicating that food can greatly affect its absorption.

In contrast, low-calcium meals do not significantly alter eltrombopag's bioavailability, but taking it with an antacid containing aluminum and magnesium can decrease its systemic exposure by approximately 70%. Overall, eltrombopag was well tolerated with mild to moderate side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: two single-dose, open-label, randomized-sequence, crossover studies. Williams, DD., Peng, B., Bailey, CK., et al.[2016]

In a study of 45 ATG-naïve patients with aplastic anemia, 62% achieved a hematologic response after 6 months of treatment with thrombopoietin receptor agonists (TPO-RAs), demonstrating their efficacy in this patient group.

Eltrombopag, a type of TPO-RA, was effective even in elderly patients with severe aplastic anemia who were ineligible for anti-thymocyte globulin (ATG) treatment, suggesting it is a viable alternative for those with age-related or health-related treatment restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of treatment with thrombopoietin receptor agonists in anti-thymocyte globulin-naïve patients with aplastic anemia: an observational retrospective analysis in a single institution. Iino, M., Jinguji, A., Sato, T., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA3

Results from VERIFY, a phase 3, double-blind, placebo ... During Wks 20-32, significantly more pts in the rusfertide group (76.9%) achieved a clinical response vs PBO (32.9%) (p<0.0001). The mean (SE) ...

2. takeda.com takeda.com/newsroom/newsreleases/2025/positive-topline-results-from-verify-study/

Rusfertide Demonstrates Promising Results in Phase 3 ... Protagonist and Takeda announce positive topline results from Phase 3 VERIFY study of rusfertide in patients with polycythemia Vera.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4559/533943/Final-Results-from-the-Phase-2-Revive-Study

Final Results from the Phase 2 Revive Study Investigating the ... Rusfertide consistently maintained Hct <45%, including in patients receiving therapy for ≥3 years. Platelets increased following initiation of ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212625006228

Rusfertide rapidly decreases hematocrit in patients with ... Highlights · In PV patients with Hct >48%, rusfertide rapidly and robustly decreased Hct to <45% · Rusfertide improved Hct regardless of the type ...

5. onclive.com onclive.com/view/dr-kuykendall-on-quality-of-life-outcomes-with-rusfertide-in-polycythemia-vera

Dr Kuykendall on Quality of Life Outcomes With Rusfertide ... Therefore, rusfertide has demonstrated the ability to control hematocrit, decrease the necessity for phlebotomy, and improve the QOL in patients ...

6. takedaoncology.com takedaoncology.com/news/news-releases/positive-topline-results-from-verify-study/

Rusfertide Demonstrates Promising Results in Phase 3 ... Protagonist and Takeda announce positive topline results from Phase 3 VERIFY study of rusfertide in patients with polycythemia vera.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06033586?intr=Rusfertide%20&rank=2

Study to Evaluate the Long-term Safety of Rusfertide (PTG ... The goal of this clinical trial is to assess long-term safety and efficacy of rusfertide in subjects with polycythemia vera. Subjects who complete dosing with ...

8. takeda.com takeda.com/newsroom/newsreleases/2025/polycythemia-vera-rusfertide-study/

Rusfertides Phase 3 Trial for Polycythemia Vera at ASCO ... Rusfertide Phase 3 study at ASCO 2025 shows reduced phlebotomy and improved hematocrit control in patients with PV.