A Phase 3 Study of Rusfertide in Patients With Polycythemia Vera (VERIFY)

• ClinicalTrials.gov Identifier: NCT05210790
• Recruitment Status: Recruiting
• First Posted: January 27, 2022
• Last Update Posted: March 5, 2024
• Sponsor: Protagonist Therapeutics, Inc.
• Information provided by (Responsible Party): Protagonist Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 14, 2022
• First Posted Date: January 27, 2022
• Last Update Posted Date: March 5, 2024
• Actual Study Start Date: April 1, 2022
• Estimated Primary Completion Date: February 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2022)

Proportion of subjects achieving a response who receive rusfertide compared to placebo. [ Time Frame: Week 20 through Week 32 ]

Response is defined as absence of phlebotomy eligibility.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 14, 2022)

• Comparison of mean number of phlebotomies between rusfertide and placebo. [ Time Frame: Week 0 to Week 32 ]
• Proportion of subjects with HCT values <45% for rusfertide and placebo. [ Time Frame: Week 0 to Week 32 ]
• Comparison mean change from baseline in total fatigue score based on PROMIS Short Form between rusfertide and placebo. [ Time Frame: Week 32 ]
• Comparison of mean change from baseline in total MFSAF total score. [ Time Frame: Week 32 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 3 Study of Rusfertide in Patients With Polycythemia Vera
• Official Title: A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300) in Patients With Polycythemia Vera
• Brief Summary: The study is designed to evaluate the safety and efficacy of rusfertide in subjects with polycythemia vera (PV) in maintaining hematocrit control and in improving symptoms of PV.
• Detailed Description: Phase 3 study in approximately 250 subjects previously diagnosed with polycythemia vera (PV) who require phlebotomy on a routine basis. There is a 32-week period during which rusfertide or placebo will be added-on to each subject's ongoing therapy for polycythemia vera which may include phlebotomy only or phlebotomy plus stable doses of either of hydroxyurea, interferon and/or ruxolitinib. All subjects who successfully complete the double blind 32-week portion of the study will receive rusfertide for 124 weeks. Approximately 6 and 12 months after their last dose of rusfertide, subjects will have a post-study contact (e.g. by phone) for safety.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, Double-blind (Part 1a):

Subjects will be randomized in a blinded fashion to 32 weeks of rusfertide or placebo added-on to each subject's ongoing treatment for polycythemia vera.

Open-label (Part 1b + Part 2):

Open-label treatment phase during which all subjects who complete Part 1a successfully will receive rusfertide for 124 weeks.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Polycythemia Vera

Intervention

• Drug: Placebo
  Placebo
• Drug: Rusfertide
  Experimental drug

Study Arms

• Experimental: Rusfertide
  Rusfertide (32 Weeks) - Rusfertide (124 Weeks Open-label)
  Intervention: Drug: Rusfertide
• Experimental: Placebo
  Placebo (32 Weeks) - Rusfertide (124 Weeks Open-label)
  Interventions:

  • Drug: Placebo
  • Drug: Rusfertide

• Publications *: Pemmaraju N, Kuykendall A, Kremyanskaya M, Ginzburg Y, Ritchie E, Gotlib J, Gerds A, Palmer J, Valone F, O'Connor P, Modi N, Gupta S, Hoffman R, Verstovsek S. MPN-469 Rusfertide (PTG-300) Treatment Interruption Reverses Hematological Gains and Upon Reinitiation, Restoration of Clinical Benefit Observed in Patients With Polycythemia Vera. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S338-S339. doi: 10.1016/S2152-2650(22)01462-8.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2022): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: February 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. There are additional inclusion criteria.

• Male and female subjects aged 18 (or the country specific minimum age of consent >18) years or older.
• Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera.
• At least 3 phlebotomies due to inadequate hematocrit control in 6 months before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization.

• CBC values immediately prior to randomization:

  1. Hematocrit <45%,
  2. WBC 4000/μL to 20,000/μL (inclusive), and
  3. Platelets 100,000/μL to 1,000,000/μL (inclusive)
• Subjects receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen.
• Subjects treated with phlebotomy alone at randomization must have stopped cytoreductive therapy 2 to 6 months before screening.

Main Exclusion Criteria: Subjects must meet NONE of the following exclusion criteria to be enrolled. There are additional exclusion criteria.

• Clinically meaningful laboratory abnormalities at Screening.
• Subjects who require phlebotomy at hematocrit levels lower than 45%.
• Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 2 months prior to randomization.
• Active or chronic bleeding within 2 months prior to randomization.
• History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer.
• Subjects with in situ or stage 1 squamous cell carcinoma of the skin, in situ or stage 1 basal cell carcinoma of the skin, or in situ melanoma of the skin identified during screen unless the cancer is adequately treated before randomization.
• Received Busulfan, Pipobroman or 32Phosphorus within 7 months prior to screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Director; 1-888-899-1543; ptgxclintrials@ptgx-inc.com

• Listed Location Countries: Australia, Austria, Belgium, Canada, Chile, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Mexico, Netherlands, Poland, Portugal, Spain, Turkey, United Kingdom, United States
• Removed Location Countries: China

Administrative Information

• NCT Number: NCT05210790
• Other Study ID Numbers: PTG-300-11
• 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: March 2024