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

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare in the efficacy and safety of givinostat to hydroxyurea in Jak2V617F-positive high risk polycythemia vera patients.

Official Title
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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

Conditions
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Polycythemia Vera

Intervention / Treatment
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* Drug: Givinostat Hydrochloride
* Drug: Hydroxy Urea


Participation Criteria
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Eligibility Criteria
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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) at 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Givinostat<br> | Drug: Givinostat Hydrochloride<br>* Oral. Starting dose of 50 mg BID with individualized dose titration ranging from 50 mg OD to 100 mg BID based on safety and efficacy<br>|
| Active Comparator: Hydroxyurea<br> | Drug: Hydroxy Urea<br>* Oral. Starting dose of 500 mg BID with individualized dose titration ranging from 500 mg OD to 1500 mg BID based on safety and efficacy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving a response at Week 48. | Response assessment based on: Hematocrit < 45% without phlebotomy in the prior 3 months, and White blood cell (WBC) count ≤ 10 × 109/L, and Platelet count ≤ 400 × 109/L, and Normal spleen size as measured by imaging (normal spleen size is defined as: a longitudinal diameter ≤ 12 cm for female and ≤ 13 cm for male) and During Part 2 (Week 25 to 48), absence of progressive disease, major hemorrhagic events and major thrombotic events. | week 25 - week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving a complete hematological response (CHR) at Week 48. | CHR based on: Hematocrit < 45% without phlebotomy in the prior 3 months, and White blood cell (WBC) count ≤ 10 × 109/L, and Platelet count ≤ 400 × 109/L | week 48 | 
| Time from randomization to the first observed CHR |  | Randomization - week 48 | 
| Proportion of patients with a normal spleen size at Week 48. |  | week 48 | 
| Safety and tolerability up to Week 48. |  | Randomization - week 48 |