Polycythemia VeraPhase 2NCT04057040
Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)
A Phase 2 study testing PTG-300 in people with Polycythemia Vera, run by Protagonist Therapeutics, Inc. at 16 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera
- What is being tested?
- PTG-300
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 16 sitesin 2 countries
- Study dates
- 1 Oct 2019to 17 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria: All subjects must meet ALL of the following inclusion criteria to be enrolled.
- 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.
Main Exclusion Criteria: Subjects must meet NONE of the following exclusion criteria to be enrolled:
- 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.
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
United States14 sites
University of Michigan
Ann Arbor, Michigan, 48109
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Cleveland Clinic - Taussig Cancer Center
Cleveland, Ohio, 44106
Pontchartrain Cancer Care
Covington, Louisiana, 70433
Mary Crowley Cancer Research Center
Dallas, Texas, 75230
Karmanos Cancer Center
Detroit, Michigan, 48201
Marin Cancer Care
Greenbrae, California, 94904
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mount Sinai
New York, New York, 10029
New York Presbyterian Hospital - Weill Cornell Medical Center
New York, New York, 10065
Stanford University
Palo Alto, California, 94304
Mayo Clinic - Mayo Clinic Hospital
Phoenix, Arizona, 85054
Moffitt Cancer Center
Tampa, Florida, 33612
University of Kansas
Westwood, Kansas, 66205
India2 sites
Sahyadri Super Specialty Hospital
Pune, Maharashtra, 411004
All India Institute of Medical Sciences
Rishikesh, Uttarakhand, 249203
About this study
Official title: 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.
Read the 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.
- Conditions
- Polycythemia Vera
- Being tested
- PTG-300, Placebo
- Keywords
- polycythemia vera
- Medical subject headings
- Polycythemia Vera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTG-300Drug
Active
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Dose finding PTG-300 (Part 1); PTG-300 (Part 2); Open label extension PTG-300 (Part 3) | Experimental | Not described Receives: Drug: PTG-300 |
| Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3) | Experimental | Not described Receives: Drug: PTG-300; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 weeks
Change in rate of phlebotomy events between Week 1 through Week 29 (inclusive; 28 weeks) compared to each subject's historical rate.
Measured: 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%.
Measured: 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.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2019
- Study start1 Oct 2019
- Primary completion14 Feb 2023
- Study completion17 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Polycythemia VeraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Protagonist Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04057040
- Sponsor's protocol ID
- PTG-300-04
- Status last verified
- Aug 2025
- First submitted
- 7 Aug 2019
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 38381675
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of the Hepcidin Mimetic PTG-300 in Patients With Phlebotomy-Requiring Polycythemia Vera
- ClinicalTrials.gov ID
- NCT04057040
- Acronym / sponsor ID
- PTG-300-04
- Conditions
- Polycythemia Vera
- Keywords
- polycythemia vera
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Protagonist Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 14 Feb 2023 (actual)
- Study completion
- 17 Jun 2024 (actual)
- First posted
- 14 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTG-300Active | Drug | 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) |
| PlaceboPlacebo | Drug | Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3) |
Primary outcome
Proportion of responders during the blinded randomized withdrawal period (Week 29 to Week 41).
Time frame: 12 weeks
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.
4 secondary outcomes
Change in rate of phlebotomy events between Week 17 through Week 29 (inclusive; 12 weeks) compared to each subject's historical rate.
Time frame: 12 weeks
Change in rate of phlebotomy events between Week 1 through Week 29 (inclusive; 28 weeks) compared to each subject's historical rate.
Time frame: 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.
Time frame: 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 frame: 12 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Derived from this study: PubMed 38381675Kremyanskaya 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PTG-300 in people with Polycythemia Vera, run by Protagonist Therapeutics, Inc. at 16 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of responders during the blinded randomized withdrawal period (Week 29 to Week 41). (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04057040, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.