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    The EU Clinical Trials Register currently displays   41228   clinical trials with a EudraCT protocol, of which   6756   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2012-000845-11
    Sponsor's Protocol Code Number:TIRCON2012V1
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-03-30
    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 ConcernedGermany - BfArM
    A.2EudraCT number2012-000845-11
    A.3Full title of the trial
    A randomized, double-blind, placebo-controlled trial of deferiprone in patients with pantothenate kinase-associated neurodegeneration (PKAN)
    Eine randomisierte, doppelblinde, plazebokontrollierte Studie zur Untersuchung von Deferiprone bei Patienten mit Pantothenat-Kinase assoziierter Neurodegeneration (PKAN)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An international trial of deferiprone in patients with iron storage brain disorders
    Eine internationale Studie mit Deferiprone bei Patienten, die eine Erkrankung haben, welche durch Eisenablagerungen im Gehirn verursacht wird
    A.3.2Name or abbreviated title of the trial where available
    TIRCON
    A.4.1Sponsor's protocol code numberTIRCON2012V1
    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 SponsorApoPharma Inc.
    B.1.3.4CountryCanada
    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 supportEuropean Commission (Main monetary support)
    B.4.2CountryBelgium
    B.4.1Name of organisation providing supportApoPharma (Investigational Medicinal Products support)
    B.4.2CountryCanada
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationApoPharma Inc.
    B.5.2Functional name of contact pointJohn Connelly
    B.5.3 Address:
    B.5.3.1Street Address200 Barmac Drive
    B.5.3.2Town/ cityToronto, Ontario
    B.5.3.3Post codeM9L 2Z7
    B.5.3.4CountryCanada
    B.5.4Telephone number+14164017296
    B.5.5Fax number+14164013869
    B.5.6E-mailjconnell@apopharma.com
    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 No
    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 nameDeferiprone 80 mg/mL oral solution
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    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 INNDeferiprone
    D.3.9.1CAS number 30652-11-0
    D.3.9.2Current sponsor codeV03AC02
    D.3.9.3Other descriptive nameDeferiprone
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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 Yes
    D.3.11.13.1Other medicinal product typeIron chelating Agent
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboOral solution
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pantothenate kinase-associated neurodegeneration (PKAN)
    E.1.1.1Medical condition in easily understood language
    Neurodegeneration with brain iron accumulation
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To evaluate the change in severity of dystonia (BAD scale) in patients with PKAN treated with deferiprone for 18 months compared to placebo.
    - To evaluate the patient’s global impression of condition’s improvement in patients treated with deferiprone for 18 months compared to placebo (PGI-I).
    E.2.2Secondary objectives of the trial
    - To evaluate the effect of deferiprone compared to placebo on the change in globus pallidus iron levels (MRI) (subset of patients).
    - To evaluate the effect of deferiprone compared to placebo on motor symptoms (UPDRS);
    - To evaluate the effect of deferiprone compared to placebo on a measure of functional independence (WeeFIM or FIM);
    - To evaluate the effect of deferiprone compared to placebo on quality of life (PedsQL);
    - To evaluate the effect of deferiprone compared to placebo on the patient’s quality of sleep (PSQI);
    - To evaluate the pharmacokinetics of deferiprone and its 3-O-glucuronide metabolite (subset of patients);
    - To evaluate the safety and tolerability of deferiprone in patients with PKAN.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males and females 4 years of age and older at screening visit;
    2. Patients must have PKAN, confirmed by genetic testing;
    3. Patients having a BAD total score ≥ 3 at the screening visit;
    4. Patients who have Deep Brain Stimulation (DBS) systems or Baclofen pumps in place will be eligible for the study, but they must have had a stable setting for at least two months prior to the screening visit and every effort should be made to maintain the stable setting for the duration of the study:
    • Enrollment of non-DBS patients will be given priority, to maximize the proportion that can undergo imaging;
    5. Sexually active female patients of childbearing potential must have a negative pregnancy test result at Screening Visit (if applicable; In cases where the Investigator determines there is no reasonable risk of pregnancy because of significant incapacity, pregnancy testing will not be performed);
    6. Fertile sexually active males must use an effective method of contraception or must confirm partner’s use of effective contraception;
    7. Informed consent/assent obtained before any study-related activities are undertaken;
    8. Ability and willingness to adhere to the protocol including appointments and evaluation schedule
    E.4Principal exclusion criteria
    1. Evidence of iron deficiency defined by Fe:TIBC ratio<15%, or serum ferritin <12 ng/mL;
    2. Treatment with deferiprone in the past 12 months;
    3. Previous failure of treatment with deferiprone, or previous discontinuation of treatment with deferiprone due to adverse events;
    4. Evidence of abnormal liver or renal function (serum liver enzyme level(s) > 3 times upper limit of normal at screening) or clinically significant abnormal creatinine levels at screening visit;
    5. Disorders associated with neutropenia (ANC < 1.5 x 109/L) or thrombocytopenia (platelet count < 50 x 109/L) in the 12 months preceding the initiation of the study medication. Exception: for patients whose neutropenia was attributed by the treating physician to episodes of infection or to drugs associated with a decline in the neutrophil count and in whom the ANC has fully recovered at the screening visit;
    6. Pregnant or nursing females, females planning to become pregnant, and females of childbearing potential who are sexually active and are unwilling, or unable, to use an acceptable method of contraception
    according to local requirements;
    7. Initiation or discontinuation of treatment with baclofen, trihexyphenidyl, clonazepam, tizanidine within 30 days prior to baseline; treatment with botox within 60 days of baseline; and initiation or discontinuation of treatment with tetrabenazine within 90 days prior to baseline;
    8. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the baseline visit;
    9. Currently taking iron chelators;
    10. Patients who, in the opinion of the physician, represent a high medical or psychological risk;
    11. History of or active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements;
    12. Patients and patient’s legal representative (if applicable) with a mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation;
    13. Baclofen pump placement less than two months prior to the beginningof the study.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy Endpoints:
    Co-Primary:
    - Change in the Barry-Albright Dystonia Scale (BAD) total score from baseline to Month 18 in patients treated with deferiprone compared to placebo, as assessed by central blinded evaluation of video-tapes;
    - Patient’s Global Impression of Improvement (PGI-I) from baseline to Month 18 in patients treated with deferiprone compared to placebo.
    Study will be considered positive if both co-primary endpoints reach statistical significance.
    E.5.1.1Timepoint(s) of evaluation of this end point
    BAD: Baseline, 6m, 12m, 18m.
    PGI-I: 6m, 12m, 18m.
    E.5.2Secondary end point(s)
    Efficacy Endpoints:
    Secondary (deferiprone vs. placebo):
    1. Proportion of patients with improved or unchanged BAD scale total score between baseline and Month 18 (responder analysis).
    2. Change from baseline to Month 18 in BAD scale score per body region (eyes, mouth, neck, trunk, each upper and lower extremity), as assessed by central blinded evaluation of video-tapes
    3. Proportion of patients showing an improvement on PGI-I at the Month 18 visit (responder analysis);
    4. Change from baseline to Month 18 in globus pallidus iron levels as measured by MRI R2* (subset of patients).
    5. Change from baseline to Month 18 in UPDRS Parts I, II, III and VI scores, respectively;
    6. Change from baseline to Month 18 in global WeeFIM score (or FIM for patients > 18 years);
    7. Change from baseline to Month 18 in WeeFIM (or FIM for patients > 18 years) score per item;
    8. Change from baseline to Month 18 in quality of life (PedsQL);
    9. Change from baseline to Month 18 in quality of sleep (PSQI).

    Safety Endpoints:
    1. Frequency of Adverse Events (AEs);
    2. Frequency of Serious Adverse Events (SAEs);
    3. Discontinuation due to AEs;
    4. Hematology assessments;
    5. Blood clinical biochemistry assessments;
    6. ECG.

    Pharmacokinetic Endpoints:

    Steady state pharmacokinetics of deferiprone and its 3-O-glucuronide metabolite will be assessed in a subset of up to 24 patients over 12 hours. The following standard pharmacokinetic parameters will be derived from plasma concentrations of deferiprone:
    - Cmax
    - Tmax
    - Cmin
    - AUCSS
    - T½
    - Vd/F
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary endpoints: Baseline, and 2m, 3m, 6m, 9m, 12m, 15m, 18m and follow-up; except Brain MRI: Baseline and 18m.
    Safety endpoints
    - Physical examination: at Screening, 1.5m, 3m, 6m, 12m,18m and Follow-up.
    - Hematology: at Screening, weekly after dosing starts, 1.5m, 3m, 6m, 12m,18m and Follow-up.
    - Biochemistry: at Screening, 1.5m, 3m, 6m, 12m, 18m.
    - ECG: at Screening and 18m.
    - Adverse events and SAEs: at each study visits and by phone at weeks 1, 2, 3, 4, 5, 6 and 2m, 3m, 6m, 9m, 15m, 18m and Follow-up.
    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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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
    Germany
    Italy
    Poland
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    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
    Based on the total individual study duration of 18 months, the last patient will have their final study visit at month 34, followed by analysis and interpretation of the results.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months34
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months34
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 72
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 36
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 36
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 18
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children > 4 years
    Adults with legal representative
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 65
    F.4.2.2In the whole clinical trial 90
    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)
    If the preliminary evidence indicates that the medicine is safe and effective for the specified indication, after the end of the study deferiprone will be offered to patients (irrespective of whether they were in the deferiprone or in the placebo arm) until approval of the product for that indication or withdrawal of the drug for that indication occurs.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation TIRCON
    G.4.3.4Network Country Germany
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-07-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-05-02
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-10-21
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