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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42732   clinical trials with a EudraCT protocol, of which   7035   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
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    Summary
    EudraCT Number:2014-001772-55
    Sponsor's Protocol Code Number:XM02-ONC-201
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-12-03
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2014-001772-55
    A.3Full title of the trial
    A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Efficacy, and Immunogenicity of Daily Subcutaneous Administration of 5 μg/kg tbo-filgrastim in Infants, Children and Adolescents with Solid Tumors without Bone Marrow Involvement
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study to assess the safety and effectiveness of tbo-filgrastim in infants,children and adolescents with solid tumors without bone marrow involvement
    A.4.1Sponsor's protocol code numberXM02-ONC-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02190721
    A.5.4Other Identifiers
    Name:IND Number:Number:103188
    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 SponsorTEVA Pharmaceutical Industries Ltd
    B.1.3.4CountryIsrael
    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 supportTeva Pharmaceutical Industries Ltd.
    B.4.2CountryIsrael
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerckle GmbH a member of the Ratiopharm Group, a subsidiary of Teva Pharmaceutical Industries Ltd.
    B.5.2Functional name of contact pointClinical Project Physician
    B.5.3 Address:
    B.5.3.1Street AddressGraf-Arco-Strasse 3
    B.5.3.2Town/ cityUlm
    B.5.3.3Post code89079
    B.5.3.4CountryGermany
    B.5.4Telephone number+49731402 3891
    B.5.5Fax number+49731402 7656
    B.5.6E-mailandreas.lammerich@ratiopharm.de
    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 Tevagrastim
    D.2.1.1.2Name of the Marketing Authorisation holderTeva GmbH
    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 nametbo-filgrastim (US) filgrastim (EU)
    D.3.2Product code XM02
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNfilgrastim
    D.3.9.1CAS number 121181-53-1
    D.3.9.2Current sponsor codeXM02
    D.3.9.4EV Substance CodeSUB07627MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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
    Chemotherapy induced Neutropenia
    E.1.1.1Medical condition in easily understood language
    Decrease in some types of white blood cells
    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 HLT
    E.1.2Classification code 10029355
    E.1.2Term Neutropenias
    E.1.2System Organ Class 100000004851
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to assess the safety and tolerability of 5 μg/kg tbo-filgrastim in the pediatric population with solid tumors without bone marrow involvement.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are to assess the pharmacokinetics using sparse
    sampling strategy, pharmacodynamics, efficacy, and immunogenicity of tbo-filgrastim in this patient population.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients may be included in the study only if they meet all of the following criteria:
    a. Male or female infants, children and adolescents aged 1 month to <16 years.
    b. Patients with solid tumors without bone marrow involvement (ie, non-myeloid neoplasms), who are scheduled to receive myelosuppressive CTX.
    c. Body weight ≥5 kg.
    d. Written informed consent provided by parent(s)/legal representative(s)
    e. Patients must have an initial diagnosis and histologic proof of their malignancy, recurrence of their disease, clear radiographic or biopsy evidence is required within 4 weeks prior to study entry.
    f. All enrolled subjects should have signed consent for a CTX regimen that is known to be myelotoxic, with counts expected to drop below the ANC of 0.5 × 109/L for at least 3 days. These regimens would include at least 1 of the following:
    Etoposide
    doxorubicin
    ifosfamide
    cyclophosphamide
    g. Patients must have an ANC >1 × 109/L and a platelet count >100 × 109/L at the start of CTX.
    h. Normal cardiac, renal, and hepatic function.
    i. All subjects must have a life expectancy of 12 weeks or more.
    j. Performance Status: Lansky performance score >60 (age 1 to <16 years).
    k. Adequate contraceptive use.
    E.4Principal exclusion criteria
    Patients will be excluded from participating in this study if they meet any of the following criteria:
    a. Bone marrow involvement.
    b. Active myelogenous leukemia or history of myelogenous leukemia.
    c. Previous treatment with colony-stimulating factors (G-CSF, granulocyte-macrophage
    colony-stimulating factor, Interleukin 11 [IL-11]) less than 6 weeks prior to study entry.
    d. Known hypersensitivity to any component of this product.
    e. History of congenital neutropenia or cyclic neutropenia.
    f. Any illness or condition that in the opinion of the investigator may affect the safety of the patient or the evaluation of any study endpoint.
    g. Pregnant or nursing female patients.
    h. Do not agree to use adequate contraceptive.
    i. Prior bone marrow or stem cell transplant, or prior radiation to ≥25% of bone marrow within the 4 weeks prior to the first tbo-filgrastim dose.
    j. Ongoing active infection or history of infectious disease within 2 weeks prior to the screening visit.
    k. Treatment with lithium at screening or planned during the study.
    l. Participation in an interventional clinical study within 30 days or 5 half-lives of the investigational product before enrollment, whichever is longer.
    E.5 End points
    E.5.1Primary end point(s)
    Safety Measures and Endpoints
    The safety of tbo-filgrastim will be assessed by evaluating the following:
    adverse event reports throughout the study clinical laboratory test results at screening and at the end-of-study visit vital signs measurements at screening, throughout the study treatment, and at the end-of-study visit
    Electrocardiography (ECG) findings at screening, pre-dose, and 4 and 6 hours after the first tbo-filgrastim administration, and at the end-of-study visit
    physical examination results at screening and at the end-of-study visit concomitant medication usage throughout the study local tolerability at the injection site at 1 hour (±30 min) after each study drug injection spleen sonography assessments at screening, on day 4 of tbo-filgrastim treatment, at the end-of-study visit, and if the patient reports left upper abdominal and/or shoulder tip pain.

    ADA assessment prior to the first tbo-filgrastim dministration, at the end-of-study visit, and at 30 days and 3 months after the last tbo-filgrastim study drug treatment in the first cycle.
    survival at 90 day follow-up.

    Pharmacokinetic Measures and Endpoints
    The pharmacokinetic measure for this study is serum concentration of tbo-filgrastim.
    Blood samples for pharmacokinetics will be obtained on study day 1 within 1 hour prior to tbofilgrastim
    administration (pre-dose) and at 2, 4, 6, 8, and 12 hours thereafter.

    Pharmacodynamic Measures and Endpoints
    Blood samples for ANC measurement will be obtained within 1 hour prior to tbo-filgrastim
    administration on study day 1 and on days 5, 6, 7, 10, 12, and 15 (optional if day 15 coincides with CTX-day 21).
    The pharmacodynamic measure for this study is ANC in blood (see Section 7.2.1).

    Efficacy Measures and Endpoint
    The efficacy measures for this study are axillary or external ear temperature and ANC in blood
    (see Section 8.1).

    The primary outcome variables and endpoints for this study are safety
    evaluations. Statistical Considerations: The overall sample size of 50 is considered sufficient to allow exploratory analysis.
    Data will be evaluated using statistical approaches for exploratory data analyses.
    No powered primary endpoints
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety at end of study visit and immunogenicity at day 30 and 90 of the follow up period, survival at day 90
    E.5.2Secondary end point(s)
    The secondary objectives are to assess the pharmacokinetics using sparse sampling strategy, pharmacodynamics, efficacy, and immunogenicity of tbo-filgastrim
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of study (D21, following cycle 1).
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    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
    Bulgaria
    Croatia
    Hungary
    Poland
    Romania
    Russian Federation
    Serbia
    Ukraine
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    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: 50
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 10
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 20
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 20
    F.1.2Adults (18-64 years) No
    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 of the lower age limit
    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 35
    F.4.2.2In the whole clinical trial 50
    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)
    Standard of Care
    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 Decision2015-01-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-18
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-04-03
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