Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)

NCT04057040 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: PTG-300-04
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 16

Brief Summary

This is a Phase 2 study with an open-label dose escalation phase followed by a blinded withdrawal phase and an open label extension. The study is designed to monitor the PTG-300 safety profile and to obtain preliminary evidence of efficacy of PTG-300 for the treatment of phlebotomy-requiring polycythemia vera.

Conditions

Polycythemia Vera

Keywords

polycythemia vera

Outcome Measures

Primary Outcomes (1)

• Proportion of responders during the blinded randomized withdrawal period (Week 29 to Week 41).

  A subject will be considered a responder during the blinded randomized withdrawal phase if hematocrit control is maintained without phlebotomy eligibility. "Phlebotomy eligibility" is defined as any one of the following criteria being met: * hematocrit ≥45% that was ≥3% higher than Week 29 pre-randomization hematocrit value, or * hematocrit \>48%, or * an increase of ≥5% in hematocrit compared to Week 29 pre-randomization hematocrit value.

  12 weeks

Secondary Outcomes (4)

• Change in rate of phlebotomy events between Week 17 through Week 29 (inclusive; 12 weeks) compared to each subject's historical rate.

  12 weeks

• Change in rate of phlebotomy events between Week 1 through Week 29 (inclusive; 28 weeks) compared to each subject's historical rate.

  28 weeks

• Proportion of subjects achieving a response at Week 29, with response defined as having achieved the absence of "phlebotomy eligibility" during the efficacy evaluation phase beginning at Week 17 and continuing to Week 29.

  12 Weeks

• Proportion of subjects with reduction in the rate of phlebotomy events beginning at the Week 17 visit and continuing to Week 29 (12 weeks) compared to each subject's historical rate.

  12 Weeks

Study Arms (2)

Dose finding PTG-300 (Part 1); PTG-300 (Part 2); Open label extension PTG-300 (Part 3)

EXPERIMENTAL

Drug: PTG-300

Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3)

EXPERIMENTAL

Drug: PTG-300; Drug: Placebo

Interventions

PTG-300 DRUG

Active

Dose finding PTG-300 (Part 1); PTG-300 (Part 2); Open label extension PTG-300 (Part 3); Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3)

Placebo DRUG

Placebo

Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3)

Eligibility Criteria

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

You may qualify if:

• Male and female subjects aged 18 years or older.
• Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera.
• Records of all phlebotomies performed for at least 28 weeks (preferably up to 52 weeks) before dosing are available.
• Subjects who are not receiving cytoreductive therapy must have been discontinued from any prior cytoreductive therapy for at least 24 weeks before screening and have recovered from any adverse events due to cytoreductive therapy.
• Subjects receiving cytoreductive therapy with hydroxyurea, interferon, or ruxolitinib must have received cytoreductive therapy for at least 24 weeks and be on a stable dose or have a decreasing dose (Medical Monitor approval required) for at least 8 weeks before dosing and with no planned change in dose.

You may not qualify if:

• Active or chronic bleeding within 4 weeks of screening.
• Meets the criteria for post-PCV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT).
• Known primary or secondary immunodeficiency.
• Any surgical procedure requiring general anesthesia within 1 month prior to screening or planned elective surgery during the study.

Sponsors & Collaborators

• Protagonist Therapeutics, Inc.: lead

Study Sites (16)

Mayo Clinic - Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Kansas

Westwood, Kansas, 66205, United States

Location

Pontchartrain Cancer Care

Covington, Louisiana, 70433, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

New York Presbyterian Hospital - Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Cleveland Clinic - Taussig Cancer Center

Cleveland, Ohio, 44106, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Sahyadri Super Specialty Hospital

Pune, Maharashtra, 411004, India

Location

All India Institute of Medical Sciences

Rishikesh, Uttarakhand, 249203, India

Location

Related Publications (1)

• Kremyanskaya M, Kuykendall AT, Pemmaraju N, Ritchie EK, Gotlib J, Gerds A, Palmer J, Pettit K, Nath UK, Yacoub A, Molina A, Saks SR, Modi NB, Valone FH, Khanna S, Gupta S, Verstovsek S, Ginzburg YZ, Hoffman R; REVIVE Trial Investigators. Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera. N Engl J Med. 2024 Feb 22;390(8):723-735. doi: 10.1056/NEJMoa2308809.

  PMID: 38381675 DERIVED

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 open label, Part 2 blinded, Part 3 open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1: 28 week open-label dose escalation phase in which each subject's dose of PTG-300 is titrated to achieve a hematocrit \<45%. Part 2: 12-week blinded randomized withdrawal phase. Subjects are randomized 1:1 to continue PTG-300 or to receive placebo. Part 3: Up to 3 year open label extension.

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 14, 2019
• Study Start: October 1, 2019
• Primary Completion: February 14, 2023
• Study Completion: June 17, 2024
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

US (14); IN (2)