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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Polycythemia Vera
• Intervention / Treatment: Drug: Givinostat Hydrochloride; Drug: Hydroxy Urea

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Domenico Cieri; Phone Number: +39 02 6443 1; Email: patientadvocacy@italfarmacogroup.com

Study Locations

• United States
  • California
    • Redlands, California, United States, 92373
      • Recruiting
      • Emad Ibrahim, Md, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Italfarmaco

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 19, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Polycythemia Vera; Polycythemia; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Histone Deacetylase Inhibitors; Hydroxyurea; Givinostat hydrochloride
• Other Study ID Numbers: DSC/08/2357/32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No