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

Polycythemia Vera Clinical Trial

— GIV-IN PV  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06093672
• Other study ID #: DSC/08/2357/32
• Status: Recruiting
• Phase: Phase 3
• Start date: March 26, 2024
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: Italfarmaco
• Contact: Domenico Cieri
• Phone: +39 02 6443 1
• Email: patientadvocacy[@]italfarmacogroup.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Emad Ibrahim, MD, Inc	Redlands	California
United States	University of Utah - Huntsman Cancer Institute - PPDS	Salt Lake City	Utah
United States	VA Puget Sound Health Care System - NAVREF - PPDS	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Italfarmaco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Time from randomization to the first observed CHR		Randomization - week 48
Secondary	Proportion of patients with a normal spleen size at Week 48.		week 48
Secondary	Safety and tolerability up to Week 48.		Randomization - week 48