Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE)

Phase 2

Active, not recruiting

• Conditions: Polycythemia Vera
• Interventions: Drug: PTG-300; Drug: Placebo

• Registration Number: NCT04057040
• Lead Sponsor: Protagonist Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2019-08-07
• Study First Submitted QC: 2019-08-13
• Study First Posted: 2019-08-14
• Study Start: 2019-10-01
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-14
• Last Update Posted: 2023-11-15
• Primary Completion: 2025-10-15
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose finding PTG-300 (Part 1); PTG-300 (Part 2); Open label extension PTG-300 (Part 3)	PTG-300	-
Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3)	PTG-300	-
Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3)	Placebo	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.	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%.
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.

Trial Locations

Locations (16)

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Karmanos Cancer Center; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic - Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Marin Cancer Care; 🇺🇸 Greenbrae, California, United States

University of Kansas; 🇺🇸 Westwood, Kansas, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Mount Sinai; 🇺🇸 New York, New York, United States

Cleveland Clinic - Taussig Cancer Center; 🇺🇸 Cleveland, Ohio, United States

Pontchartrain Cancer Care; 🇺🇸 Covington, Louisiana, United States

Mary Crowley Cancer Research Center; 🇺🇸 Dallas, Texas, United States

New York Presbyterian Hospital - Weill Cornell Medical Center; 🇺🇸 New York, New York, United States

Sahyadri Super Specialty Hospital; 🇮🇳 Pune, Maharashtra, India

All India Institute of Medical Sciences; 🇮🇳 Rishikesh, Uttarakhand, India

Stanford University; 🇺🇸 Palo Alto, California, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Center for Cancer and Blood Disorders; 🇺🇸 Bethesda, Maryland, United States