Clinical trial NCT04057040: Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)
Official title: A Phase 2 Study of the Hepcidin Mimetic PTG-300 in Patients With Phlebotomy-Requiring Polycythemia Vera
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Polycythemia Vera
Keywords: polycythemia vera
Lead sponsor: Protagonist Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of responders during the blinded randomized withdrawal period (Week 29 to Week 41).
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in rate of phlebotomy events between Week 17 through Week 29 (inclusive; 12 weeks) compared to each subject's historical rate.
timeFrame: 12 weeks
measure: Change in rate of phlebotomy events between Week 1 through Week 29 (inclusive; 28 weeks) compared to each subject's historical rate.
timeFrame: 28 weeks
measure: 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.
timeFrame: 12 Weeks
measure: 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.
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Mayo Clinic Hospital
state: Arizona
city: Greenbrae
country: United States
facility: Marin Cancer Care
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Westwood
country: United States
facility: University of Kansas
state: Kansas
city: Covington
country: United States
facility: Pontchartrain Cancer Care
state: Louisiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Center
state: Ohio
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Pune
country: India
facility: Sahyadri Super Specialty Hospital
state: Maharashtra
city: Rishikesh
country: India
facility: All India Institute of Medical Sciences
state: Uttarakhand
Study officials:
References: