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.

Tracking Information

• First Submitted Date: August 7, 2019
• First Posted Date: August 14, 2019
• Last Update Posted Date: November 15, 2023
• Actual Study Start Date: October 1, 2019
• Estimated Primary Completion Date: October 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2021)

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.

Original Primary Outcome Measures (submitted: August 13, 2019)

• Proportion of subjects with absence of phlebotomy eligibility [ Time Frame: Week 42 ]
  "Phlebotomy eligibility" is defined as a confirmed hematocrit >45% that was ≥3% higher than baseline level or a confirmed hematocrit >48%
• Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) [ Time Frame: 42 weeks ]
  The Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) is a validated tool for measurement of symptoms for patients. The MPN-SAF includes 14 disease related symptoms scored from 0 (absent) to 10 (worst imaginable) and is used to calculate a total symptom score (TSS; sum of 14 individual symptom scores).
• Number of Participants with Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 [ Time Frame: 101 weeks ]

Current Secondary Outcome Measures (submitted: September 21, 2021)

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

Original Secondary Outcome Measures (submitted: August 13, 2019)

• Change from baseline in serum iron [ Time Frame: 42 weeks ]
• Change from baseline in transferrin saturation (TSAT) [ Time Frame: 42 weeks ]
• Change from baseline in serum transferrin [ Time Frame: 42 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: Polycythemia Vera

Intervention

• Drug: PTG-300
  Active
• Drug: Placebo
  Placebo

Study Arms

• Experimental: Dose finding PTG-300 (Part 1); PTG-300 (Part 2); Open label extension PTG-300 (Part 3)
  Intervention: Drug: PTG-300
• Experimental: Dose finding PTG-300 (Part 1); Placebo (Part 2); Open label extension PTG-300 (Part 3)
  Interventions:

  • Drug: PTG-300
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 10, 2022): 80
• Original Estimated Enrollment (submitted: August 13, 2019): 30
• Estimated Study Completion Date: January 1, 2026
• Estimated Primary Completion Date: October 15, 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India, United States

Administrative Information

• NCT Number: NCT04057040
• Other Study ID Numbers: PTG-300-04
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Protagonist Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Protagonist Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Protagonist Therapeutics, Inc.
• Verification Date: November 2023