Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)

A Phase 2 Study of the Hepcidin Mimetic PTG-300 in Patients With Phlebotomy-Requiring Polycythemia Vera

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.

Study Overview

• Status: Completed
• Conditions: Polycythemia Vera
• Intervention / Treatment: Drug: Placebo; Drug: PTG-300

Detailed Description

Phase 2 study in approximately sixty subjects previously diagnosed with Polycythemia Vera who require phlebotomy on a routine basis. There is a 28 week dose finding phase to identify a dose that maintains hematocrit <45%. Subjects who successfully complete the dose finding phase will be entered into a 12 week randomized withdrawal phase to confirm the response. Subsequently patients will enter into an up to 3 year open label extension to investigate long term safety.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Specialty Hospital
  • Uttarakhand
    • Rishikesh, Uttarakhand, India, 249203
      • All India Institute of Medical Sciences
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Mayo Clinic Hospital
  • California
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Pontchartrain Cancer Care
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital - Weill Cornell Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic - Taussig Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria: All subjects must meet ALL of the following inclusion criteria to be enrolled.

1. Male and female subjects aged 18 years or older.
2. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera.
3. Records of all phlebotomies performed for at least 28 weeks (preferably up to 52 weeks) before dosing are available.
4. 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.
5. 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.

Main Exclusion Criteria: Subjects must meet NONE of the following exclusion criteria to be enrolled:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose finding PTG-300 (Part 1); PTG-300 (Part 2); Open label extension PTG-300 (Part 3)	Drug: PTG-300; Active
Experimental: Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3)	Drug: Placebo; Placebo; Drug: PTG-300; Active

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	"Phlebotomy eligibility" in Part 1 is defined as a hematocrit ≥45% that was ≥3% higher than baseline level (defined as Part 1 pre-dose Day 1) or a hematocrit >48%.	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.	Time to "phlebotomy eligibility" from Week 29 to Week 41/End of Part 2.	12 Weeks

Collaborators and Investigators

• Sponsor: Protagonist Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): February 14, 2023
• Study Completion (Actual): June 17, 2024

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: polycythemia vera
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: PTG-300-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No