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    Summary
    EudraCT Number:2018-001983-49
    Sponsor's Protocol Code Number:UX023-CL205
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-10-10
    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
    H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
    Expand All   Collapse All
    A. Protocol Information
    A.2EudraCT number2018-001983-49
    A.3Full title of the trial
    An Open-Label, Phase 2 Study to Assess the Safety, Pharmacodynamics, and Efficacy of KRN23 in Children from 1 to 4 Years Old with X-linked Hypophosphatemia (XLH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess the efficacy and safety of KRN23 in children from 1 to 4 years old with X-linked Hypophosphatemia (XLH)
    A.4.1Sponsor's protocol code numberUX023-CL205
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02750618
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/007/2018
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUltragenyx Pharmaceutical Inc
    B.1.3.4CountryUnited States
    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 supportUltragenyx Pharmaceutical Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUltragenyx Pharmaceutical Inc
    B.5.2Functional name of contact pointClinical Operation
    B.5.3 Address:
    B.5.3.1Street Address60 Leveroni Court, Suite 200
    B.5.3.2Town/ cityNovato
    B.5.3.3Post code94949
    B.5.3.4CountryUnited States
    B.5.4Telephone number1415475-6521
    B.5.6E-mailRVakil@ultragenyx.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 CRYSVITA 10 mg solution for injection CRYSVITA 20 mg solution for injection CRYSVITA 30 mg solution for injection
    D.2.1.1.2Name of the Marketing Authorisation holderKyowa Kirin Holdings B.V.
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1351
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    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 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 Yes
    D.3.11.13.1Other medicinal product typeFully Human Monoclonal Antibody
    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 disorder of hypophosphatemia, renal phosphate wasting, and the most common inheritable form of rickets. In XLH patients, excess circulating fibroblast growth factor (FGF23) impair phosphate reabsorption in the kidney. Chronic low serum phosphorus levels lead to defective bone mineralization and, consequently, to rickets in children and osteomalacia in adults, the two major pathologic outcomes of the hypophosphatemia.
    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
    The primary objectives of the study are to:
    • Establish the safety profile of KRN23 for the treatment of XLH in children between 1 and 4 years old
    • Determine the pharmacodynamic (PD) effects of KRN23 treatment on serum phosphorus and other PD markers that reflect the status of phosphate homeostasis in children between 1 and 4 years old with XLH
    E.2.2Secondary objectives of the trial
    Additional study objectives are to assess the following in children between 1 and 4 years old with XLH
    • Effects of KRN23 on rickets
    • Effects of KRN23 on growth and lower extremity deformity
    • KRN23 drug concentration levels (PK)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Individuals eligible to participate in this study must meet all of the following criteria:
    1) Male or female, aged ≥1 year and < 5 years
    2) PHEX mutation or variant of uncertain significance in either the patient or in a directly related family member with appropriate X-linked inheritance 3) Biochemical findings associated with XLH including:
    a. Serum phosphorus < 3.0 mg/dL (0.97 mmol/L)*
    b. Serum creatinine within age-adjusted normal range*
    4) Radiographic evidence of rickets; at least 5 subjects will be required to have a rickets severity score (RSS) at the knee of at least 1.5 points as determined by central read
    5) Willing to provide access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history
    6) Provide written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
    7) 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
    * Criteria to be determined based on fasting (min. 4 hours) values collected at Baseline
    E.4Principal exclusion criteria
    Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
    1) Unwilling to stop treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analog (e.g. calcitriol, alfacalcidol) during the screening period and for the duration of the study
    2) Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale:
    0 = Normal
    1 = Faint hyperechogenic rim around the medullary pyramids
    2 = More intense echogenic rim with echoes faintly filling the entire pyramid
    3 = Uniformly intense echoes throughout the pyramid
    4 = Stone formation: solitary focus of echoes at the tip of the pyramid
    3) Planned or recommended orthopedic surgery including staples, 8-plates or osteotomy, within the clinical trial period
    4) Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits*
    5) Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study
    6) Presence of a concurrent disease or condition that would interfere with study participation or affect safety
    7) History of recurrent infection or predisposition to infection, or of known immunodeficiency
    8) Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments
    * Criteria to be determined based on fasting (min. 4 hours) values collected at Baseline
    E.5 End points
    E.5.1Primary end point(s)
    Safety:
    Safety will be evaluated by the incidence, frequency and severity of adverse events (AEs) and serious adverse events (SAEs), including clinically significant changes in laboratory test results from baseline to scheduled time points.
    General Safety Variables will include the following:
    • Vital signs and weight
    • Physical examinations
    • Glomerular filtration rate (GFR)
    • Chemistry, hematology, and urinalysis, including additional KRN23/XLH biochemical parameters of interest (serum calcium, intact parathyroid hormone [iPTH], 25-hydroxyvitamin D [25(OH)D], amylase, lipase, and creatinine; and urinary calcium and creatinine)
    • Anti-KRN23 antibody testing and dose-limiting toxicities
    • Concomitant medications
    • Electrocardiogram (ECG)
    Ectopic Mineralization Safety Assessments include:
    • Renal ultrasound

    Pharmacodynamics:
    The primary efficacy endpoint is the change from baseline over time in serum phosphorus. Additional pharmacodynamics assessments include:
    • Change from baseline over time in serum 1,25(OH)2D and urinary phosphorus
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week -6 to Baseline, Baseline, Week 1, every two weeks from Week 2 to 64
    E.5.2Secondary end point(s)
    • Change in rickets at Week 40 as assessed by the Radiograph Global Impression of Change (RGI C) global score
    • Change in rickets at Week 64 as assessed by RGI-C global score
    • Change from baseline in RSS total score at Weeks 40 and 64
    • Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score at Weeks 40 and 64
    • Change in recumbent length/standing height from baseline to post-treatment study time points in cm, height-for-age z-scores, and percentiles. Historical growth records may be used to evaluate change in growth velocity
    • Change and percent change from baseline over time in serum alkaline phosphatase (ALP)
    • Serum KRN23 concentrations at indicated study time points
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week -6 to Baseline, Baseline, Week 1, every two weeks from Week 2 to 64
    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 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.8.3 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 Yes
    E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
    United States
    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
    LVLS
    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 months6
    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: 13
    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: 3
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 10
    F.1.1.6Adolescents (12-17 years) No
    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 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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Recruitment including pediatric patients 1 to 4 years old.
    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 13
    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)
    All subjects completing study UX023-CL205 will be offered to enroll into a treatment extension study.
    G. Investigator Networks to be involved in the Trial
    H.4 Third Country in which the Trial was first authorised
    H.4.1Third Country in which the trial was first authorised: United States
    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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