Randomized, Open-label, Multicenter Phase 3 Study to Assess the Efficacy and Safety of GIVinostat Versus Hydroxyurea IN JAK2V617F-positive High-risk Polycythemia Vera Patients: the GIV-IN PV TRIAL

Core Treatment - Inclusion Criteria: * Patients must have been diagnosed with PV according to the 2016 WHO criteria before randomization * Patients must have JAK2V617F-positive disease * Patients with PV must meet the definition of HR for thrombosis (i.e., HR) within 3 years before screening as follows: * Age ≥ 60 years, and/or * Prior thrombosis. * Patients must be in need of treatment at screening, defined by the presence of at least one of the following: * HCT ≥ 45% or HCT \< 45% with at least 1 phlebotomy performed in the 3 months before screening, or * WBC count \> 10 × 109/L, or * PLT count \> 400 × 109/L. * Patients must have normalized HCT (i.e., HCT \< 45%) at randomization Extended Treatment - Inclusion Criteria * Patients must have completed the Week 48 visit of the DSC/08/2357/32 core treatment phase and: 1. if the patient received givinostat, a complete hematological response (CHR) at Week 48 shall be achieved 2. if the patient received HU, did not achieve a CHR (see above for the definition) at Week 48 Core Treatment phase - Exclusion Criteria * Patients pre-treated with HU with a documented history of resistance or intolerance to HU defined by the original ELN criteria * Patients with a QTcF value of \> 450 msec for males and \> 460 msec for females at the Screening visit (as the mean of 3 consecutive readings 5 minutes apart in the event a first ECG demonstrates a prolonged QTcF interval); congenital or acquired history of QTc prolongation or ventricular arrhythmias, at the Screening visit * Splanchnic thrombosis and/or thrombosis of the cerebral venous sinuses and/or splenectomy in the medical history * Patients with clinically significant cardiovascular disease * Patients with myocardial infarction, stroke or unstable angina within the 6 months prior 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 (radioactive isotope) therapy. * Patients being treated concurrently with any investigational agent or prior participation in an interventional clinical study within the 30 days prior to screening or within 5 half-lives of the investigational product, whichever is longer. * Pregnant or nursing women Extended treatment phase - Exclusion criteria * For patients randomized to givinostat in the core treatment phase - Patients with a QTcF value at Week 48 of \> 500 msec * For patients randomized to HU in the core treatment phase: * PLT count ≤ 150 × 109/L at Week 48 * ANC \< 1.2 × 109/L at Week 48 * Uncontrolled hypertriglyceridemia at Week 48 * Patients with a QTcF value at Week 48 of \> 450 msec for males and \> 460 msec for female