Clinical trial
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
Name
DSC/08/2357/32
Description
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.
Trial arms
Trial start
2024-03-26
Estimated PCD
2026-07-01
Trial end
2026-07-01
Status
Recruiting
Phase
Early phase I
Treatment
Givinostat Hydrochloride
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
Arms:
Givinostat
Hydroxy Urea
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
Arms:
Hydroxyurea
Size
220
Primary endpoint
Proportion of patients achieving a response at Week 48.
week 25 - week 48
Eligibility criteria
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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 220, 'type': 'ESTIMATED'}}
Updated at
2024-05-07
1 organization
2 products
1 indication
Organization
ItalfarmacoProduct
GivinostatIndication
Polycythemia VeraProduct
Hydroxy Urea