Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera

Inclusion Criteria:

• Patients must have been diagnosed with PV according to the 2016 WHO criteria within 3 years before randomization

• Patients must have JAK2V617F-positive disease

• Patients with PV must meet the definition of HR for thrombosis (i.e., HR) atscreening as follows:

• Age ≥ 60 years, and/or

• Prior thrombosis.

• Patients must be in need of treatment at screening, defined by the presence of atleast one of the following:

• HCT ≥ 45% or HCT < 45% with at least 1 phlebotomy performed in the 3 monthsbefore screening, or

• WBC count > 10 × 109/L, or

• PLT count > 400 × 109/L.

• Patients must have normalized HCT (i.e., HCT < 45%) at randomization

Exclusion Criteria:

• Patients pre-treated with HU with a documented history of resistance or intoleranceto HU defined by the original ELN criteria

• Patients with a QTcF value of > 450 msec for males and > 460 msec for females at theScreening visit (as the mean of 3 consecutive readings 5 minutes apart in the eventa first ECG demonstrates a prolonged QTcF interval); congenital or acquired historyof QTc prolongation or ventricular arrhythmias, at the Screening visit

• Splanchnic thrombosis and/or thrombosis of the cerebral venous sinuses and/orsplenectomy in the medical history

• Patients with clinically significant cardiovascular disease

• Patients with myocardial infarction, stroke or unstable angina within the 6 monthsprior to screening.

• Patients with inadequate liver or renal function at screening

• Uncontrolled hypertriglyceridemia at screening, i.e., triglycerides ˃ 1.5 × ULN

• Previous treatment with a JAK2 or HDAC inhibitor or 32-phosphorus (radioactiveisotope) therapy.

• Patients being treated concurrently with any investigational agent or priorparticipation in an interventional clinical study within the 30 days prior toscreening or within 5 half-lives of the investigational product, whichever islonger.

• Pregnant or nursing women