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   43851   clinical trials with a EudraCT protocol, of which   7283   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:2008-001252-52
    Sponsor's Protocol Code Number:CZOL446H2337
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2012-03-02
    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
    H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
    Expand All   Collapse All
    A. Protocol Information
    A.2EudraCT number2008-001252-52
    A.3Full title of the trial
    A multicenter, randomized, double-blind, placebo controlled efficacy and safety trial of intravenous (i.v.)
    zoledronic acid, twice yearly compared to placebo in osteoporotic children treated with glucocorticoids for
    chronic inflammatory conditions.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Assessment of the efficacy and safety of Aclasta in pediatric patients (5-17 years of age) in the treatment of osteoporosis following glucocorticoid intended to treat chronic inflammatory conditions
    A.4.1Sponsor's protocol code numberCZOL446H2337
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT00799266
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/151/2010
    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 Arzneimittel GmbH
    B.5.2Functional name of contact pointH. Gebbing
    B.5.3 Address:
    B.5.3.1Street AddressRoonstrasse 25
    B.5.3.2Town/ cityNurnberg
    B.5.3.3Post code90429
    B.5.3.4CountryGermany
    B.5.4Telephone number0049911 273 12 721
    B.5.5Fax number0049911 273 15 721
    B.5.6E-mailheintz.gebbing@novartis.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    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.3.9.3Other descriptive nameAclasta
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    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 (aged 5 to 17 years old) population treated with glucocorticoids (i.v. or oral) for chronic inflammatory conditions (including rheumatic conditions or inflammatory bowel disease)
    E.1.1.1Medical condition in easily understood language
    Disease of bones that leads to an increased 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 14.1
    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
    Primary Efficacy objective:
    - Demonstrate that zoledronic acid administered every 6 months 0.05 mg/kg (max 5 mg) demonstrates superiority
    relative to placebo for the change in lumbar spine (LS) areal bone mineral density (BMD) Z-score at Month 12
    relative to baseline.
    Safety objective:
    - Demonstrate that zoledronic acid is safe for the treatment of osteoporotic children treated with glucocorticoids
    for chronic inflammatory conditions through the monitoring of relevant clinical and laboratory safety parameters
    E.2.2Secondary objectives of the trial
    - Evaluate between-treatment differences for the change in LS areal BMD Z-score at Month 6 relative to baseline
    - Evaluate between-treatment differences for the change from baseline in LS and total body BMC at 6 and 12
    months
    - Evaluate between-treatment differences for the change in serum P1NP, NTX, BSAP & TRAP-5b at Months 6
    and 12 relative to baseline
    - Evaluate between-treatment differences for the proportion of patients with new vertebral fractures at Month 12
    relative to baseline
    - Evaluate between-treatment differences for change in vertebral morphometry at Month 12 relative to baseline
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Children, male or female, between 5 and 17 years of age at visit 1 of the study
    - Confirmed diagnosis of a chronic inflammatory condition, including rheumatic conditions or inflammatory bowel disease (IBD)
    - Treatment with systemic glucorticoids (i.v. or oral) within the 12 months preceding enrollment in the sudy (any duration)
    - Lumbar Spine areal BMD Z-score of -1.0 or worse and evidence of at least 1 vertebral compression fracture (at least Genant Grade 1 vertebral compression or radiographic signs of vertebral compression) confirmed by central reading
    - Ability to obtain informed consent/assent

    Amendment:
    - Evidence of at least 1 vertebral compression fracture of Genant Grade 1 or higher or
    radiographic signs of vertebral fracture)within 1 month from Screening visit, confirmed by central reading.
    Radiographic signs of fracture
    include loss of endplate parallelism, vertebral buckling and endplate interruption.

    AND/OR
    1 or more, low-trauma, lower extremity long-bone fracture which occurred sometime within the 2 years PRECEDING, OR following the diagnosis of the underlying disease (rheumatologic condition/IBD), confirmed by central reading.

    AND/ OR
    2 or more, low-trauma, upper extremity long-bone fractures which occurred
    sometime within the 2 years PRECEDING, OR following the diagnosis of the
    underlying disease (rheumatologic condition/IBD), confirmed by central reading.
    E.4Principal exclusion criteria
    - Any prior use of osteoporosis or bone-modifying therapy, such as bisphosphonates, sodium flouride, calcitonin, calcitriol, SERMs (Selective Estrogen-Receptor Modulators), LHRH agonists, Growth Hormone (GH) or medroxyprogesterone
    - Patients who have received testosterone or estrogen therapy may only be included in the trial if these therpies were given as part of physiological replacement in the setting of documented hormonal deficiencies
    - Any prior history of malignancy
    - Any medical condition that might interfere with the evaluation of LS BMD, such as severe scoliosis or spinal fusion. Patients with less than 3 evaluable vertebrae by DXA evaluation on the region of interest (ROI) L1-L4, as confirmed by the central imaging laboratory, will not be considered eligiblefor this study
    - Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at screening
    - Vitamin D deficiency (serum 25-hydroxy vitamin D concentrations of <16 ng/ml or <40 nmol/L) at screening
    - Renal impairment defined as an estimated glomerular filtration rate (GFR)<35 ml/min/1.73 m2 at screening based on the Schwartz formula
    - A serum creatinine increase between Visit 1 and Visit 2 greater than 0.5 mg/dL (44.2 μmol/L)
    - History of hyperparathyroidism or hyperthyroidism within 1 year of screening
    - History of hypothyroidism unless on a stable treatment regimen for > 6 months, with at least one documented normal TSH and FT4 levels during this 6 month period
    - History of sarcoidosis
    - Diagnosis of cative uveitis (symptomatic or asymptomatic) at the time of enrollment of the study
    - Female patients of child bearing potential are eligible only if they are: (1) not pregnant/non-lactating; (2) are sexually abstinent or are surgically sterile and (3) if sexually active, must be practicing a medically acceptable form of birth control for greater than 2 months prior to screenng visit. Females of childbearing potential who are sexually active must agree to continue to practice their birth control during the trial and at least 1 year after completing the trial and must consent to a pregnancy test prior to every dose administration
    - History of primary bone disease (osteogenesis imperfecta, iodopathic juvenile osteoporosis, rickets/
    osteomalacia)
    - Non-ambulatory patients who require wheelchair assistance for mobility
    - History of Kawasaki's disease or Henoch-Schonlein Purpura
    E.5 End points
    E.5.1Primary end point(s)
    The primary objective of the study is to demonstrate that zoledronic acid administered every 6 months 0.05 mg/kg (max 5 mg) demonstrates superiority relative to placebo for the change in lumbar spine (LS) areal bone mineral density (BMD) Z-score at Month 12 relative to baseline.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months
    E.5.2Secondary end point(s)
    - Evaluate between-treatment differences for the change in LS areal BMD Z-score at Month 6 relative to baseline
    - Evaluate between-treatment differences for the change from baseline in LS and total body BMC at 6 and 12 months
    - Evaluate between-treatment differences for the change in serum P1NP, NTX, BSAP & TRAP-5b at Months 6 and 12 relative to baseline
    - Evaluate between-treatment differences for the proportion of patients with new vertebral fractures at Month 12 relative to baseline
    - Evaluate between-treatment differences for change in vertebral morphometry at Month 12 relative to baseline
    E.5.2.1Timepoint(s) of evaluation of this end point
    12 months
    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 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 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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 Will this trial be conducted at a single site globally? No
    E.8.4 Will this trial be conducted at multiple sites globally? Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
    Australia
    Canada
    New Zealand
    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 Patient Last Visit (LPLV)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days4
    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: 92
    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: 42
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 50
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 92
    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)
    Open label treatment with Aclasta will be offered to patients who agree to participate in a one year extension study but otherwise further treatment will be determined by the treating physician.
    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 Covance IVRS (Project Manager)
    G.4.3.4Network Country United States
    H.4 Third Country in which the Trial was first authorised
    H.4.1Third Country in which the trial was first authorised: Canada
    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-Fri Apr 19 22:09:02 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA