Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)

• ClinicalTrials.gov Identifier: NCT04057040
• Recruitment Status: Active, not recruiting
• First Posted: August 14, 2019
• Last Update Posted: November 15, 2023
• Sponsor: Protagonist Therapeutics, Inc.
• Information provided by (Responsible Party): Protagonist Therapeutics, Inc.

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
Polycythemia Vera	Drug: PTG-300; Drug: Placebo	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 (Clinical Trial)
• Estimated 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.

• 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: October 1, 2019
• Estimated Primary Completion Date: October 15, 2025
• Estimated Study Completion Date: January 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). [ 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.

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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 12 Weeks ]
   Time to "phlebotomy eligibility" from Week 29 to Week 41/End of Part 2.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic - Mayo Clinic Hospital

Phoenix, Arizona, United States, 85054

United States, California

Marin Cancer Care

Greenbrae, California, United States, 94904

Stanford University

Palo Alto, California, United States, 94304

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Kansas

University of Kansas

Westwood, Kansas, United States, 66205

United States, Louisiana

Pontchartrain Cancer Care

Covington, Louisiana, United States, 70433

United States, Maryland

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States, 20817

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Karmanos Cancer Center

Detroit, Michigan, United States, 48201

United States, New York

Mount Sinai

New York, New York, United States, 10029

New York Presbyterian Hospital - Weill Cornell Medical Center

New York, New York, United States, 10065

United States, Ohio

Cleveland Clinic - Taussig Cancer Center

Cleveland, Ohio, United States, 44106

United States, Texas

Mary Crowley Cancer Research Center

Dallas, Texas, United States, 75230

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

India

Sahyadri Super Specialty Hospital

Pune, Maharashtra, India, 411004

All India Institute of Medical Sciences

Rishikesh, Uttarakhand, India, 249203

Sponsors and Collaborators

Protagonist Therapeutics, Inc.

More Information

• Responsible Party: Protagonist Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04057040
• Other Study ID Numbers: PTG-300-04
• First Posted: August 14, 2019
• Last Update Posted: November 15, 2023
• Last Verified: November 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Protagonist Therapeutics, Inc.:

polycythemia vera

Additional relevant MeSH terms:

Polycythemia Vera; Polycythemia; Hematologic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Myeloproliferative Disorders