search
Back to results

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

Primary Purpose

Polycythemia Vera

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Givinostat Hydrochloride
Hydroxy Urea
Sponsored by
Italfarmaco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycythemia Vera

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Givinostat

    Hydroxyurea

    Arm Description

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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
    Time from randomization to the first observed CHR
    Proportion of patients with a normal spleen size at Week 48.
    Safety and tolerability up to Week 48.

    Full Information

    First Posted
    October 10, 2023
    Last Updated
    October 19, 2023
    Sponsor
    Italfarmaco
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT06093672
    Brief Title
    Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera
    Acronym
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 2023 (Anticipated)
    Primary Completion Date
    July 2026 (Anticipated)
    Study Completion Date
    July 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Italfarmaco

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No

    5. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Polycythemia Vera

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    220 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Givinostat
    Arm Type
    Experimental
    Arm Title
    Hydroxyurea
    Arm Type
    Active Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Givinostat Hydrochloride
    Intervention Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Hydroxy Urea
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    Proportion of patients achieving a response at Week 48.
    Description
    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.
    Time Frame
    week 25 - week 48
    Secondary Outcome Measure Information:
    Title
    Proportion of patients achieving a complete hematological response (CHR) at Week 48.
    Description
    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 Frame
    week 48
    Title
    Time from randomization to the first observed CHR
    Time Frame
    Randomization - week 48
    Title
    Proportion of patients with a normal spleen size at Week 48.
    Time Frame
    week 48
    Title
    Safety and tolerability up to Week 48.
    Time Frame
    Randomization - week 48

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs