Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)

Sponsor
Protagonist Therapeutics, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04057040
Collaborator
(none)
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16
2
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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

Study Type:
Interventional
Anticipated Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention 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.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 (Participant, Investigator, Outcomes Assessor)
Masking Description:
Part 1 open label, Part 2 blinded, Part 3 open label
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of the Hepcidin Mimetic PTG-300 in Patients With Phlebotomy-Requiring Polycythemia Vera
Actual Study Start Date :
Oct 1, 2019
Anticipated Primary Completion Date :
Oct 15, 2025
Anticipated Study Completion Date :
Jan 1, 2026

Arms and Interventions

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: PTG-300
Active

Drug: Placebo
Placebo

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

  3. 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]

    "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%.

  4. 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]

    Time to "phlebotomy eligibility" from Week 29 to Week 41/End of Part 2.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Mayo Clinic - Mayo Clinic Hospital Phoenix Arizona United States 85054
2 Marin Cancer Care Greenbrae California United States 94904
3 Stanford University Palo Alto California United States 94304
4 Moffitt Cancer Center Tampa Florida United States 33612
5 University of Kansas Westwood Kansas United States 66205
6 Pontchartrain Cancer Care Covington Louisiana United States 70433
7 Center for Cancer and Blood Disorders Bethesda Maryland United States 20817
8 University of Michigan Ann Arbor Michigan United States 48109
9 Karmanos Cancer Center Detroit Michigan United States 48201
10 Mount Sinai New York New York United States 10029
11 New York Presbyterian Hospital - Weill Cornell Medical Center New York New York United States 10065
12 Cleveland Clinic - Taussig Cancer Center Cleveland Ohio United States 44106
13 Mary Crowley Cancer Research Center Dallas Texas United States 75230
14 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
15 Sahyadri Super Specialty Hospital Pune Maharashtra India 411004
16 All India Institute of Medical Sciences Rishikesh Uttarakhand India 249203

Sponsors and Collaborators

  • Protagonist Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Protagonist Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT04057040
Other Study ID Numbers:
  • PTG-300-04
First Posted:
Aug 14, 2019
Last Update Posted:
Apr 14, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Protagonist Therapeutics, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 14, 2022