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    The EU Clinical Trials Register currently displays   37700   clinical trials with a EudraCT protocol, of which   6177   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2018-000202-37
    Sponsor's Protocol Code Number:BUR02
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-04-30
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2018-000202-37
    A.3Full title of the trial
    A Phase 3b Open-label Study of the Anti-FGF23 Antibody,
    Burosumab (KRN23) in Adult Patients with X-linked
    Hypophosphatemia (XLH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3b Open-label Study of the Anti-FGF23 Antibody,
    Burosumab (KRN23) in Adult Patients with X-linked
    Hypophosphatemia (XLH)
    A.4.1Sponsor's protocol code numberBUR02
    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 SponsorKyowa Kirin Pharmaceutical Development Ltd
    B.1.3.4CountryUnited Kingdom
    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 supportKyowa Kirin Pharmaceutical Development Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIcon Clinical Research Ltd
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street Address100 Milton Park Ave
    B.5.3.2Town/ cityAbingdon
    B.5.3.3Post codeOX14 4RY
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number4407931653684
    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. name CRYSVITA
    D. of the Marketing Authorisation holderKyowa Kirin Ltd
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1351
    D.3 Description of the IMP
    D.3.1Product namerecombinant human igG1 monoclonal antibody to fibrolblast growth factor23 (FGF-23)
    D.3.2Product code KRN23
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubconjunctival use
    Subcutaneous use
    Intravascular use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBUROSUMAB
    D.3.9.2Current sponsor codeKRN23
    D.3.9.4EV Substance CodeSUB184986
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 30
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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
    XLH is a rare, genetic disorder that is serious, chronically debilitating and represents an
    unmet medical need. This genetic deficiency is estimated to occur in about 1:20,000 live
    births (Burnett et al. 1964), (Imel et al. 2005). XLH is the most common inherited form of
    rickets and the most common inherited defect in renal tubular phosphate transport. XLH is
    transmitted as an X-linked dominant disorder (Dixon et al. 1998).
    E.1.1.1Medical condition in easily understood language
    Inheritable form of rickets
    E.1.1.2Therapeutic area Body processes [G] - Bones and nerves physological processes [G11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10016206
    E.1.2Term Familial hypophosphataemic rickets
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To continue to evaluate the long-term efficacy and safety of burosumab as a treatment for adult
    patients with XLH and to provide continued treatment for subjects previously enrolled in
    UX023-CL303 and UX023-CL304 clinical trials.
    E.2.2Secondary objectives of the trial
    The objectives are to assess the efficacy and
    safety of burosumab administered via subcutaneous (SC) injections every 4 weeks and to allow
    subjects continued access to burosumab up until December 2019 or until commercially available, with
    no cost to the patient, in each individual country.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Subjects who provide written informed consent after the nature of the study has been
    explained, and prior to any research-related procedures.
    2) Subject who successfully completed Study UX023-CL303 or UX023-CL304. Subjects should have completed the study up to and including the final study visit.Subjects who were prematurely discontinued due to adverse events, Sponsor's decision or Investigator's decision will not be enrolled in this study. Subjects' enrolment is not dependent on any response to Primary or Secondary endpoints in studies UX023-CL303 or UX023CL304.or those which did not complete the studies for reasons other than serious adverse events or protocol deviations may be considered on a case by case basis.
    3) Willing to provide access to prior medical records for the collection of historical growth,
    biochemical and radiographic data, and disease history.
    4) Must, in the opinion of the investigator, be willing and able to complete all aspects of the
    study, adhere to the study visit schedule and comply with the assessments.
    5) Females of child-bearing potential must have a negative urine pregnancy test at Screening and
    be willing to have additional pregnancy tests during the study. Females considered not to be of
    child-bearing potential include those who have been in menopause for at least two years prior
    to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total
    hysterectomy or bilateral salpingo-oophorectomy. If sexually active, male and female subjects
    must be willing to use one highly effective method of contraception for the duration of the
    E.4Principal exclusion criteria
    1) Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted
    normal limits and deemed as clinically significant in the opinion of the investigator.
    2) Presence of a concurrent disease or condition that would interfere with study participation
    or affect safety in the opinion of the investigator or Sponsor.
    3) Use of any investigational product other than burosumab or investigational medical device
    within 30 days prior to Screening, or requirement for any investigational agent prior to
    completion of all scheduled study assessments.
    4) Subjects with major protocol deviations in Study UX023-CL303 or UX023-CL304 which
    in the view of the investigator places the subject at high risk of poor treatment compliance or of not completing the study. Or higher than a grade 3 treatment related hypersensitivity reaction or burosumab related hypersensitivity reaction reported as a SAE will be excluded.
    E.5 End points
    E.5.1Primary end point(s)
    Primary efficacy objective: Establish the effect of burosumab treatment on maintaining serum
    phosphorous levels to within normal range in adults with XLH.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Until December 2021or reimbursed commercially available product is supplied
    E.5.2Secondary end point(s)
    Key secondary objectives: Evaluate the effect of burosumab treatment in adults with XLH on:
    o Pre-existing (identified during UX023-CL303 or UX023-CL304) pseudofracture
    healing and enthesopathy
    o Patient impression of their improvement (compared to baseline in this study and
    previous UGX023 study)
    o Walking ability as measured by Six Minute Walk Test (6MWT)
    o Mobility as measured by Timed Up and Go (TUG) test completion time
    o Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Brief
    Pain Inventory (BPI) and Brief Fatigue Inventory (BFI)
    o Pharmacodynamic:
     Serum phosphorus
     Serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D)
     Urinary phosphorus
    hosphate reabsorption: ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR).
    Carboxy-terminal cross-linked telopeptide of type I collagen (CTx), procollagen type 1 N-propeptide (P1NP), bone alkaline phosphatase and alkaline phosphatase
    Safety Objectives:
    Establish the long-term safety and tolerability profile of burosumab in the treatment of
    adults with XLH including adverse events (AEs), ectopic mineralization risk, cardiovascular effects and immunogenicity profile.
    Assess impact of burosumab on pre- and post-prandial serum
    concentrations of phosphorus and calcium in a subset of study subjects.
    E.5.2.1Timepoint(s) of evaluation of this end point
    not applicable
    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 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. 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 No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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 years3
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months10
    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 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.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 40
    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)
    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 Decision2018-09-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-13
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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