A Randomized Phase II, Open-Label Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Polycythemia Vera (PV) or Essential Thrombocythemia (ET) Who Are Resistant or Intolerant to Hydroxyurea
- Has had a diagnosis of hydroxyurea resistant or intolerant polycythemia vera (PV) or
essential thrombocythemia (ET).
- Polycythemia vera or essential thrombocythemia defined according to the revised WHO
- Polycythemia vera resistance or intolerance to hydroxyurea is defined as polycythemia
vera patients on hydroxyurea with a hematocrit >45%, or phlebotomy twice in the last
6 months and at least once in the last 3 months.
- Essential thrombocythemia resistance or intolerance to hydroxurea is defined as
essential thrombocythemia patients on HU with platelet count >600 x 10x9/L.
Dose Expansion Phase (polycythemia vera) and 600 mg/day group (essential thrombocythemia):
- Has had a diagnosis of polycythemia vera and essential thrombocythemia according to
the revised WHO 2008 criteria.
- PV patients must be resistant or intolerant to hydroxyurea.
- ET patients must be resistant or intolerant to hydroxyurea.
- Provide written informed consent to participate.
- Less than 18 years of age.
- Participation in any study of an investigational agent (drug, biologic, device)
within 30 days prior to initiation of study drug, unless during non-treatment phase.
(Prior treatment with another JAK2 inhibitor is allowed.)
- Unwilling to comply with scheduled visits, treatment plans, laboratory assessments,
and other study-related procedures.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 or 4 at study
- Active malignancy other than polycythemia vera or essential thrombocythemia, except
adequately treated basal cell carcinoma and squamous cell carcinoma of the skin,
cervical carcinoma in situ, or other malignancies that have been stable and off
therapy for ≥5 years.
- Major surgery within 28 days or radiation within 3 months prior to initiation of
- Active acute infection requiring antibiotics.
- Known human immunodeficiency virus or acquired immunodeficiency syndrome-related
- Uncontrolled congestive heart failure (New York Heart Association Classification 3 or
4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral
artery bypass surgery, transient ischemic attack, or pulmonary embolism within 3
months prior to initiation of study drug.
- Any severe acute or chronic medical, neurological, or psychiatric condition or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration, may interfere with the informed consent process and/or
with compliance with the requirements of the study, or may interfere with
interpretation of study results and, in the Investigator's opinion, would make the
patient inappropriate for entry into this study.
- Inadequate organ function.
- Known active (acute or chronic) Hepatitis A, B, or C; and Hepatitis B and C carriers.
- Prior history of chronic liver disease (eg, chronic alcoholic liver disease,
autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis,
hemachromatosis, non-alcoholic steatohepatitis [NASH]).
- Concomitant treatment with or use of drugs or herbal agents known to be at least
moderate inhibitors or inducers cytochrome P450 3A4 (CYP3A4).
- Presence of any gastric or other disorder that would inhibit absorption of oral
- Known hypersensitivity to any excipients in the study drug formulation.
- Women of childbearing potential, unless using effective contraception while on study
- Men who partner with a woman of childbearing potential, unless they agree to use
effective contraception while on study drug.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.