Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2013-003583-31
    Sponsor's Protocol Code Number:CINC424B2401
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-02-25
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2013-003583-31
    A.3Full title of the trial
    Randomized, open label, multicenter phase IIIb study evaluating the efficacy and safety of ruxolitinib versus best available therapy in patients with polycythemia vera who are hydroxyurea resistant or intolerant (Response 2)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Ruxolitinib efficacy and safety in patients with HU resistant or intolerant polycythemia vera vs best available therapy
    A.3.2Name or abbreviated title of the trial where available
    Response 2
    A.4.1Sponsor's protocol code numberCINC424B2401
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNovartis Pharma Services AG
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Jakavi
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRuxolitinib
    D.3.2Product code INC424
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRuxolitinib
    D.3.9.1CAS number 1092939-17-7
    D.3.9.2Current sponsor codeINC424
    D.3.9.3Other descriptive nameRUXOLITINIB PHOSPHATE
    D.3.9.4EV Substance CodeSUB32897
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Polycythemia vera resistant or intolerant to hydroxyurea
    E.1.1.1Medical condition in easily understood language
    Polycythemia vera
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10036061
    E.1.2Term Polycythemia vera
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    efficacy of ruxolitinib to BAT as assessed by Hct control at Week 28
    E.2.2Secondary objectives of the trial
    Key
    1. efficacy of RUX to BAT assessed by complete hematological remission at W28
    Other
    2. efficacy of RUX to BAT assessed by durable Hct control at W52 and W80
    3. efficacy of RUX to BAT assessed by durable complete hematological remission at W52 & W80
    4. assess phlebotomies over time
    5. change in Hct
    6. assess spleen length
    7. ECOG status change
    8. efficacy of RUX to BAT assessed by partial remission based on ELN+IWG-MRT criteria at W28
    9. efficacy of RUX to BAT assessed by durable partial remission based on ELN+IWG-MRT criteria at W52 & W80
    10. efficacy of BAT pts after crossover
    11. efficacy of RUX pts measured by durable Hct control at W104, 156, 208, 260
    12. efficacy of RUX pts measured by durable complete hematological remission at W104, 156, 208, 260
    13. efficacy of RUX pts by partial remission based on ELN+IWG-MRT criteria at W104, 156, 208, 260
    14. transformation-free survival
    15. OS
    16. changes in PRO
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Confirmed diagnosis of PV according to the 2008 World Health Organization criteria
    2. Non-palpable spleen at Screening and Baseline
    3. Phlebotomy dependent, Resistant to or intolerant of hydroxyurea
    4. ECOG performance status of 0, 1 or 2.

    Other inclusion criteria as defined by protocol may apply
    E.4Principal exclusion criteria
    - Inadequate liver or renal function
    - Significant bacterial, fungal, parasitic, or viral infection requiring treatment
    - Active malignancy within the past 5 years, excluding specific skin cancers
    - Previously received treatment with a JAK inhibitor
    - Being treated with any investigational agent
    - Women who are pregnant or nursing.

    Other exclusion criteria as defined by protocol may apply.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of patients achieving Hct control at Week 28 as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8.
    Phlebotomy eligibility will be defined by:
    • Confirmed Hct > 45% that is at least 3 percentage points higher than the Hct obtained at Baseline
    Or
    • Confirmed Hct > 48%.
    The confirmation will occur 2 to 14 days subsequent to the initial observation.
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 28
    E.5.2Secondary end point(s)
    Key secondary:
    Proportion of patients achieving a complete hematological remission at Week 28 as defined by:
    • Hct control at Week 28 defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
    • WBC < 10 x109/L at Week 28, and
    • Platelets ≤ 400 x 109/L at Week 28

    Other secondary:
    1. Proportion of patients achieving a Hct control at Week 52 as defined by:
    • the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8
    In the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm. Endpoint for Week 80 is defined, similarly.
    2. Proportion of patients achieving a complete hematological remission at Week 52 as defined by:
    • Hct control at Week 52 as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, with no more than one phlebotomy eligibility occurring post randomization and prior to week 8, and
    • WBC < 10 x109/L at Week 52, and
    • Platelets ≤ 400 x 109/L at Week 52, and
    In the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm. Endpoint for Week 80 is defined, similarly.
    3. Number of phlebotomies from Baseline up to Week 28
    4. Change from Baseline in Hct at each visit
    5. Summary of spleen length by visit
    6. Change in ECOG status from baseline to Week 28.
    7. Proportion of patients achieving a partial remission at Week 28, based on the ELN and IWG-MRT criteria, as defined by:
    • MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 28 and
    • Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
    • WBC < 10 x109/L at Week 28, and
    • Platelets ≤ 400 x 109/L at Week 28, and
    • No palpable spleen at Week 28, and
    • No hemorrhagic or thrombotic events, and
    No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria).
    8. Proportion of patients who achieved partial remission at Week 52, based on the ELN and IWG-MRT criteria, as defined by:
    • MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 52, and
    • Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
    • WBC < 10 x109/L at Week 52, and
    • Platelets ≤ 400 x 109/L at Week 52, and
    • No palpable spleen at Week 52, and
    • No hemorrhagic or thrombotic events, and
    • No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria), and
    In the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm. Endpoint for Week 80 is defined, similarly.
    9. Change from Baseline (last assessment before crossover) in Hct at each scheduled visit after crossover in patients randomized to BAT who cross over to RUX
    10. Proportion of patients achieving a Hct control at Week 104 as defined by:
    • The absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104 and
    • with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8
    Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.
    11. Proportion of patients achieving a complete hematological remission at Week 104 as defined by:
    • Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
    • WBC < 10 x109/L at Week 104, and
    • Platelets ≤ 400 x 109/L at Week 104
    Endpoint for Week 156, Week 208 and Week 260 are defined, similarly
    12. Proportion of patients who achieved partial remission at Week 104, based on the ELN and IWG-MRT criteria, as defined by:
    • MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 104, and
    • Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
    • WBC < 10 x109/L at Week 104, and
    • Platelets ≤ 400 x 109/L at Week 104, and
    • No palpable spleen at Week 104, and
    • No hemorrhagic or thrombotic events, and
    • No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria), and
    Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.

    Other secondary endpoints may apply.
    E.5.2.1Timepoint(s) of evaluation of this end point
    For key secondary,
    1. week 28

    For other secondary:
    1. week 52
    2. week 52
    3. week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment
    4. week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment
    5. week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment
    6. week 28
    7. week 28
    8. week 52
    9. +4, +8, +12, +16, +20, +24 weeks after crossover
    10. week 104
    11. week 104
    12. week 104
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    document medical resource utilization (MRU)
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Best available therapy (BAT)
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA45
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    Canada
    France
    Germany
    Hungary
    India
    Israel
    Italy
    Korea, Republic of
    Spain
    Switzerland
    Turkey
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study will occur 5 years and 30 days from the date when the
    last patient was randomized.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 105
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 25
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 95
    F.4.2.2In the whole clinical trial 130
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Following the last visit, patients who are still receiving ruxolitinib and having benefit in the opinion of the investigator may continue to receive ruxolitinib. Patients will be transitioned to a local supply of ruxolitinib, off study, which will be reimbursed by Novartis where necessary. If local supply is not available to a patient at that time, s/he may be able to receive ruxolitinib under a separate protocol if approved by the country regulatory authority.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-04-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-03-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-04-07
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Apr 23 22:39:56 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA