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    Summary
    EudraCT Number:2010-020399-41
    Sponsor's Protocol Code Number:CZOL446H2337E1
    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:2017-09-05
    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 number2010-020399-41
    A.3Full title of the trial
    A 1-year, multicenter, open-label extension to CZOL446H2337 to evaluate safety and efficacy of zoledronic acid twice yearly in osteoporotic children treated with glucocorticoids
    A CZOL446H2337 vizsgálat egyéves, multicentrikus, nyílt-elrendezésű, kiterjesztett vizsgálata az évente kétszer alkalmazott zoledronsav biztonságosságának és hatásosságának értékelésére glükokortikoidokkal kezelt, osteoporosisban szenvedő gyermekeknél
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A one year extension study to CZOL446H2337, multi-center, to evaluate safety and efficacy of zoledronic acid given to all patients every six months in children with weakened bone treated with steroids
    A zoledronsav 12 hónapos megfigyeléses vizsgálata osteoporosisban szenvedő gyermekeknél és serdülőknél
    A.4.1Sponsor's protocol code numberCZOL446H2337E1
    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 organisationNovartis Pharma AG
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressForum 1, Novartis Campus
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4056
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number +41 61 32 41111
    B.5.5Fax number +41 61 32 48001
    B.5.6E-mailclinicaltrial.enquiries@novartis.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 Yes
    D.2.1.1.1Trade name Aclasta®
    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 nameAclasta®
    D.3.2Product code ZOL446
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNZOLEDRONIC ACID
    D.3.9.1CAS number 118072-93-8
    D.3.9.2Current sponsor codeZOL446
    D.3.9.4EV Substance CodeSUB00176MIG
    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
    Treatment of osteoporosis in a paediatric population (aged 5 to 19 years old) treated with systemic glucocorticoids (i.v. or oral)
    E.1.1.1Medical condition in easily understood language
    Disease of bones that leads to an increase risk of fracture
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10031282
    E.1.2Term Osteoporosis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate that zoledronic acid given long-term, over an additional 12 months from the Core study (CZOL446H2337), is safe for the treatment of osteoporotic children treated with glucocorticoids.
    E.2.2Secondary objectives of the trial
    To evaluate
    Group 1
    •change from baseline1(Core study) in LS areal BMD Z-score, LS and total body BMC at Month 18 & 24
    • the change from baseline1 in serum P1NP, NTX, BSAP and TRAP-5b at Month 18 & 24
    •change from baseline1 in pain using FPS-R at Month 15, 18, 21 & 24
    •change from baseline1 in bone age & 2nd metacarpal cortical width at month 24
    Group 2:
    •change from baseline2 (Extension study) in LS areal BMD Z-score, LS and total body BMC at Month 6 & 12
    •change from baseline2 in serum P1NP, NTX, BSAP and TRAP-5b) at Month 6 & 12
    •change from baseline2 in pain using FPS-R at Month 3, 6, 9 & 12
    •change from baseline2 in bone age and 2nd metacarpal cortical width at month 12
    Both groups:
    •proportion of patients with new clinical vertebral fractures and new morphometric vertebral fracture during 12 month period.
    To demonstrate zoledronic acid is safe for treatment of osteoporotic children treated with glucocorticoids
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Signed consent/assent to study participation.
    Group 1:
    •Children and adolescents, male or female, between 6 to 19 years of age who met the inclusion criteria for entry into the Core study and who took at least one dose of study drug in and have completed Visit 8 of the CZOL446H2337 Core study.
    • Patient must be enrolled into the extension at visit 9 up to 10 months after at Visit 5 of the Core study.
    • Patients who followed the regimen of calcium and vitamin D intake as required in the Core study
    Group 2 :
    • Children and adolescents, male or female, between 5 to 17 years of age who met the inclusion criteria for entry into the Core study but were not enrolled because of clinically significant back pain from vertebral fracture and the preexisting clinical care at Investigator’s site is to treat this type of patient with a bisphosphonate.
    • Confirmed diagnosis of non-malignant conditions (including but not limited to rheumatic conditions, Inflammatory Bowel Disease, Duchenne Muscular Dystrophy, nephrotic syndrome), treated with systemic glucocorticoids (i.v. or oral)
    within the 12 months preceding enrollment in the study (any duration)
    • Lumbar Spine-BMD Z-score of - 0.5 or worse confirmed by the central imaging
    • Evidence of at least 1 vertebral compression fracture (at least Genant Grade 1 vertebral compression or radiographic signs of vertebral compression*) seen on X-ray within 1 month of or at screening visit confirmed by central reading.
    *Radiographic signs of vertebral compression fracture include loss of endplate parallelism, vertebral buckling and endplate interruption.
    E.4Principal exclusion criteria
    • Patients who demonstrated a major protocol violation in the core study (Group 1 only)
    • Prior use of bisphosphonates (Group 2 only) or sodium fluoride (doses for osteoporosis not for dental hygiene)
    • Vitamin D deficiency (serum 25-hydroxy vitamin D concentration of <20 ng/ml or <50 nmol/L) at Visit 8 (Group 1) or Visit 8A (Group 2)
    • Hypocalcaemia and hypophosphatemia: any value (age-matched) below the normal range at Visit 8 (Group 1) or Visit 8A (Group 2)
    • Renal impairment defined as an estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 based on the Schwartz formula at Visit 8 (Group 1) or Visit 8A (Group 2). Serum creatinine above the normal range at Visit 9 (Group 1) or an increase between Visit 8A and Visit 9 greater than 0.5 mg/dL (44.2 μmol/L) for Group 2.
    •Female patients of child bearing potential are eligible only if they are not pregnant/non-lactating. Females of child bearing potential must be practicing a medically acceptable form of birth control for greater than 2 months prior to screening visit and consent to pregnancy tests during the study.
    E.5 End points
    E.5.1Primary end point(s)
    Safety assessments will consist of:
    • monitoring and recording of all adverse events and serious adverse events,
    • the performance of physical examinations including oral examinations for exposed bone.
    • the regular laboratory monitoring of hematology, blood chemistry and urinalysis, regular measurement of vital signs, and
    • renal function (serum creatinine & GFR).
    E.5.1.1Timepoint(s) of evaluation of this end point
    • Monitoring and recording of all adverse events and serious adverse events:
    At each visit during the study
    • Physical examination including oral examination:
    At visits 9, 12 and Visit 15
    • Vital signs:
    Blood pressure and pulse rate: Visits 8 (Group 1 only), 8A (Group 2 only), Visits 9, 12 and 15
    • Sitting and standing height and weight measurements: Visits 8 (Group 1 only), 8A (Group 2 only), Visits 9, 12 and 15
    • Laboratory evaluations:
    Central laboratory test (hematology, biochemistry and urinalysis): Visits 8A (Group 2 only), Visits 9, 12 and 15.
    Additional lab test for renal monitoring: Visits 9, 10, 12, 13 and 15.
    E.5.2Secondary end point(s)
    The efficacy variables will be measured using the following techniques:
    • vertebral morphometric fractures
    • clinical fractures
    • DXA measurements
    • bone marker analysis
    • height measurements
    • bone age and metacarpal cortical width assessment
    • pain assessment
    E.5.2.1Timepoint(s) of evaluation of this end point
    •Vertebral morphometric fractures:
    At final visit of Core study (Group1) or Visit 8A (Group2) and Visit 15
    •Clinical fractures:
    At final visit of the Core study (Group 1) or Visit 8A (Group2) and at each Visits
    •DXA measurements:
    At final visit of Core study (Group 1) or Visit 8A (for Group 2), Visit 9 and 15.
    •Bone marker Analysis:
    At final visit of Core study (Group 1) or Visit 9 (Group 2), Visit 12 and 15
    •Height measurements:
    At final visit of Core study (Group 1) or Visit 8A/or 9 (Group 2), Visit 12 and 15
    •Bone age and metacarpal carpal cortical width assessment:
    At final visit of Core study (Group 1) or Visit 8A (Group 2) and Visit 15.
    •Pain Assessment:
    At final visit of Core study (Group 1) and Visit 9, 11, 12, 14 and 15.
    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 No
    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 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 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.8.3 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 EEA10
    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
    Canada
    Germany
    Hungary
    Italy
    Poland
    Russian Federation
    South Africa
    Turkey
    United Kingdom
    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
    Last Visit of the Last Subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months12
    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: 100
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 40
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 57
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 3
    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
    Minors under the age of 18 years old
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 100
    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)
    The investigator must provide follow-up medical care or refer for appropriate ongoing care for all patients who have ended participation in the trial, to ensure that adequate consideration is given to the protection of the patient’s interests.
    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 Decision2017-10-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-10-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-02-27
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