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    Summary
    EudraCT Number:2008-002898-12
    Sponsor's Protocol Code Number:CZOL446K2418
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-12-10
    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 ConcernedUK - MHRA
    A.2EudraCT number2008-002898-12
    A.3Full title of the trial
    An open label, Aclasta, re-treatment of relapsed patients with Paget´s disease of bone who participated in the CZOL446K2304 and CZOL446K2305 Core Registration studies
    A.3.2Name or abbreviated title of the trial where available
    NA
    A.4.1Sponsor's protocol code numberCZOL446K2418
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    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 support
    B.4.2Country
    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 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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 118072938
    D.3.9.2Current sponsor codeZOL446
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5 to mg
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Paget´s disease of the bone
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10033363
    E.1.2Term Paget's disease of bone
    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 efficacy objective is to show that patients with Paget´s disease of bone who had responded to zoledronic acid and later experienced a relapse can successfully have their total serum alkaline phosphatase (SAP) normalized within 6 months after a single 5 mg re-treatment dose of Aclasta. This objective will be demonstrated if at least 60 % of patients have their total SAP normalized within 6 months.
    E.2.2Secondary objectives of the trial
    - Determine the relative change in SAP levels at 3 months and 6 months following re-treatment with Aclasta - Collect information pertaining to the diagnosis of relapse used by practicing physicians that will define and support re-treatment guidelines for Paget´s disease of bone in patients who have previously responded to zoledronic acid treatment - Determine the adverse event profile of patients who receive a re-treatment dose of Aclasta. A safety objective will be demonstrated if the incidence of transient post-dose symptoms (PDS) is reduced by 20% relative to the incidence in the core study
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Patients must give written informed consent to participate in the study - Male or female patients who were randomized to receive zoledronic acid in the CZOL446K2304 (previously referred to as CZOL446H2304) or CZOL446K2305 (previously referred to as CZOL446H2305) pivotal studies and met the definition of responder at the 6 month post-dose visit - Confirmed relapse of Paget´s disease of the bone based on investigator´s assessment through one or more of the following: SAP that is above the ULN, bone scan consistent with relapse of Paget´s disease of bone, and/or worsening of clinical symptoms (e.g., bone pain or compression symptoms)
    E.4Principal exclusion criteria
    - A patient treated with Aclasta, who relapsed during the EOP and was treated with anti-resorptive bisphosphonate or calcitonin therapy within the past 12 months - Hypersensitivity to any drug within the class of bisphosphonates - Patients with a new diagnosis or active treatment for malignancy (other than basal cell or squamous cell skin cancer) less than or equal to 12 months prior to study entry - Patients with suspected or proven metastases at time of re-treatment - Patients who are unlikely to be able to complete the study or comply with the visit schedule and required assessments due to cancer, non-skeletal metastases or paraneoplastic syndrome or their ongoing/planned treatments - Specific exceptions to the cancer exclusion (within 12 months prior to re-treatment). Patients may be included if: Basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy have been removed, ductal Carcinoma in-situ (DCIS) has been surgically removed, carcinoma in-situ (CIS) of the uterine cervix has been surgically removed - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive urine test - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent - Reliable contraception should be maintained throughout the study and for 60 days after study drug discontinuation - Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels >40 mIU/ml and estradiol <20 pg/ml or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks prior to visit 2. In the case of oophorectomy alone, classification of a woman as post-menopausal would occur when her reproductive status has been confirmed by follow up hormone level assessment - Any disease or therapy which will interfere with the procedures or data collection of this trial - Patients with active (symptomatic or asymptomatic) iritis, uveitis or episcleritis - Calculated creatinine clearance <35 ml/min at screening visit - Serum calcium level <2.07 mmol/L - Active primary hyperparathyroidism, hyperthyroidism, hypoparathyroidism or hypothyroidism No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy objective is to show that patients with Paget´s disease of bone who had responded to zoledronic acid and later experienced a relapse can successfully have their total serum alkaline phosphatase (SAP) normalized within 6 months after a singe 5 mg re-treatment dose of Aclasta. This objective will be demonstrated if at least 60% of patients have their total SAP normalized within 6 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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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.1.3Elderly (>=65 years) Yes
    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 state13
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 30
    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 Decision2008-08-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-10-13
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-04-15
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