GIV-IN PV: Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera

Sponsor

Italfarmaco (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06093672

Collaborator

(none)

220

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Polycythemia Vera	Drug: Givinostat Hydrochloride Drug: Hydroxy Urea	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

220 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Givinostat	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
Active Comparator: Hydroxyurea	Drug: 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

Arm

Intervention/Treatment

Experimental: Givinostat

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

Active Comparator: Hydroxyurea

Drug: 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

Outcome Measures

Primary Outcome Measures

Proportion of patients achieving a response at Week 48. [week 25 - 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.

Secondary Outcome Measures

Proportion of patients achieving a complete hematological response (CHR) at Week 48. [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
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Italfarmaco

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Italfarmaco

ClinicalTrials.gov Identifier:

NCT06093672

Other Study ID Numbers:

DSC/08/2357/32

First Posted:

Oct 23, 2023

Last Update Posted:

Oct 23, 2023

Last Verified:

Oct 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Polycythemia Vera

Polycythemia

Hydroxyurea

Givinostat hydrochloride

Study Results

No Results Posted as of Oct 23, 2023