MC# 21-13 - A Phase II Study of the Hepcidin Mimetic PTG-300 in Patients With Phlebotomy-Requiring Polycythemia Vera

  • Agent(s): PTG-300
  • Disease Type(s): Polycythemia Vera
  • Phase(s): II
  • Drug Classification(s): Other
  • Molecular Target(s): n/a

Mechanism of Action

PTG-300 mimics endogenous hepcidin, a protein primarily produced in hepatocytes, and increases hepcidin levels.  As hepcidin plays a key role in the homeostasis of systemic iron, PTG-300 may serve to normalize iron levels.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of PTG-300 can be given with an acceptable level of side effects
  • If PTG-300 can reduce the level of hematocrit in your blood
  • The effects of PTG-300 (good and bad)
  • The safety and effectiveness of PTG-300 for reducing the need for phlebotomies
  • How much of PTG-300 is absorbed into the blood and how fast it is removed
Inclusion Criteria
  1. Male and female subjects aged 18 years or older
  2. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of PV
  3. Hematocrit <45% before dosing
  4. Phlebotomy requiring defined as:
    a. Regularly spaced phlebotomies over at least 28 weeks prior to dosing.
    b. At least 3 phlebotomies during the 28 weeks prior to dosing.
    c. Last phlebotomy within approximately 12 weeks before Screening
  5. Records of all phlebotomies performed for at least 28 weeks (and preferably up to 52 weeks) before dosing
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
  7. Women of childbearing potential and men agree to use medically acceptable contraception (<1% annual failure rate) during the study and for 90 days after the last dose of study drug
  8. 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 AEs due to cytoreductive therapy
  9. 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 with no planned change in dose

Restart Inclusion Criteria

  1. Subject understands the study procedures, is willing and able to adhere to study requirements and agrees to participate in the study by giving written informed consent.
  2. Hematocrit <45% before restarting dosing
Exclusion Criteria
  1. Clinically meaningful laboratory abnormalities at Screening including, but not limited to:
    a. Absolute neutrophil count <1000/μL
    b. Platelet count <100,000/μL
    c. Estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m2
    d. Alanine aminotransferase (ALT) or aspartate aminotransferase
  2. Pregnant or lactating females
  3. Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 1 month of Screening
  4. Active or chronic bleeding within 4 weeks of Screening
  5. Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
  6. Infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 3 months of dosing; any infection requiring antimicrobial therapy within 4 weeks of dosing. Prophylactic antibodies are allowed.
  7. Any serious or unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the subject from properly providing informed consent or any condition which would jeopardize compliance with the study
  8. Known primary or secondary immunodeficiency
  9. Positive for hepatitis B or hepatitis C or known human immunodeficiency virus (HIV) infection
  10. Any surgical procedure requiring general anesthesia within 1 month prior to screening or planned elective surgery during the study
  11. History of invasive malignancies within the last 5 years, except localized cured prostate cancer, cervical cancer, and ductal carcinoma in situ (DCIS)
  12. Current or recent history of alcohol dependence or illicit drug use within 1 year prior to Screening.
  13. Subject is unable to give informed consent.
  14. Receipt of an investigational agent within 30 days of Screening.

Restart Exclusion Criteria

  1. Clinically meaningful laboratory abnormalities at restart including, but not limited to:
    1. Absolute neutrophil count <1000/μL
    2. latelet count <100,000/μL
    3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5 × upper limit of normal (ULN) or direct bilirubin >1.5 × ULN.
  2. Pregnant or lactating females.
  3. Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) during the dosing suspension period.
  4. Active or chronic bleeding within 4 weeks of restart.
  5. Infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection during dosing suspension period; any infection requiring antimicrobial therapy within 4 weeks of dosing. Prophylactic antibiotics are allowed.
  6. Any serious or unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the subject from properly providing informed consent or any condition which would jeopardize compliance with the study.
  7. Known primary or secondary immunodeficiency.
  8. Known positivity for hepatitis B or hepatitis C or human immunodeficiency virus (HIV) infection.
  9. Any surgical procedure requiring general anesthesia within 1 month prior to restarting or planned elective surgery during the study.
  10. History of invasive malignancies within the last 2 years, except non-melanoma skin cancer and localized cured prostate cancer, cervical cancer, and ductal carcinoma in situ (DCIS).
  11. Current or recent history of alcohol dependence or illicit drug use during the dosing suspension period.
  12. Subject is unable to give informed consent.
  13. Receipt of an investigational agent other than PTG-300 within 30 days prior to restarting.
  14. Initiated or increased the dose of interferon or ruxolitinib dose during the suspension period.
  15. Initiated or increased the dose of hydroxyurea for a reason other than to control erythropoiesis during the suspension period

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04057040

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Re: MC# 21-13