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Trial record 12 of 12 for:    KRN23

Efficacy and Safety of KRN23 Versus Oral Phosphate and Active Vitamin D Treatment in Pediatric Patients With X Linked Hypophosphatemia (XLH) (PIXLES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Ultragenyx Pharmaceutical Inc
Sponsor:
Collaborator:
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier:
NCT02915705
First received: May 23, 2016
Last updated: January 13, 2017
Last verified: January 2017
  Purpose
UX023-CL301 is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of KRN23 with active control (oral phosphate/active vitamin D therapy) in children with XLH (aged 1 to ≤12 years) who have radiographic evidence of rickets, open epiphyses, and have received oral phosphate/active vitamin D therapy for ≥ 6-12 consecutive months prior to screening. Approximately 60 subjects will be randomized 1:1 to receive open-label KRN23 administered by subcutaneous injection or oral phosphate and active vitamin D therapy for a total of 64 weeks.

Condition Intervention Phase
X-Linked Hypophosphatemia
Biological: KRN23
Drug: Oral Phosphate
Drug: Active Vitamin D
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Phase 3 Study to Assess the Efficacy and Safety of KRN23 Versus Oral Phosphate and Active Vitamin D Treatment in Pediatric Patients With X Linked Hypophosphatemia (XLH)

Resource links provided by NLM:


Further study details as provided by Ultragenyx Pharmaceutical Inc:

Primary Outcome Measures:
  • Improvement in rickets in children with XLH [ Time Frame: 40 weeks ]
    Change in rickets at Week 40 as assessed by the RGI-C global score compared between the KRN23 and active control groups


Secondary Outcome Measures:
  • Change in Serum Phosphorous [ Time Frame: 64 weeks ]
    Effect of KRN23 as compared with active control by change from baseline in serum phosphorous

  • Change in Serum 1,25(OH)D [ Time Frame: 64 weeks ]
    Effect of KRN23 as compared with active control by change from baseline in serum 1,25(OH)D

  • Walking ability using the Six Minute Walk Test (6MWT) [ Time Frame: 24, 40 and 64 weeks ]
    Change from baseline in total distance walked

  • Growth [ Time Frame: 24, 40 and 64 weeks ]
    Change from baseline in standing height

  • Patient/Parent reported pain, fatigue and physical function/mobility [ Time Frame: 24, 40 and 64 weeks ]
    Change from baseline using the Patient Reported Outcomes Measurement Information System (PROMIS)

  • Phamacokinetics throughout the dosing cycle [ Time Frame: 64 weeks ]
    Measure the concentration of KRN23

  • Incidence, frequency, and severity of AE's and SAE's [ Time Frame: 64 weeks ]
    Incidence compared against active control group


Estimated Enrollment: 60
Study Start Date: September 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: KRN23
Subjects randomized 1:1 to receive 0.8 mg/kg starting dose, administered every 2 weeks by subcutaneous injection.
Biological: KRN23
KRN23 is a recombinant human immunoglobulin G isotype 1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23).
Active Comparator: Active Control
Subjects randomized 1:1 to receive multiple daily doses of oral Phosphate and Active Vitamin D therapy, individualized for each subject at the Investigator's discretion.
Drug: Oral Phosphate Drug: Active Vitamin D

  Eligibility

Ages Eligible for Study:   1 Year to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged 1 to ≤12 years with radiographic evidence of rickets as determined by central read
  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: Serum phosphorus <3.0 mg/dL (0.97 mmol/L)
  4. Serum creatinine within age-adjusted normal range
  5. Serum 25(OH)D above the lower limit of normal (≥16 ng/mL) at the Screening Visit
  6. Have received both oral phosphate and active vitamin D therapy for ≥ 12 consecutive months (for children ≥3 years of age) or ≥ 6 consecutive months (for children <3 years of age) prior to the Screening Visit
  7. Willing to provide access to prior medical records for the collection of historical growth and radiographic data and disease history.
  8. Provide written or verbal assent (as appropriate for the subject and region) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
  9. 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.
  10. Females who have reached menarche must have a negative pregnancy test at Screening and undergo additional pregnancy testing during the study. If sexually active, male and female subjects must be willing to use highly effective method(s) of contraception for the duration of the study.

Exclusion Criteria:

  1. Tanner stage 4 or higher through physical examination
  2. Height percentile >50% based on country-specific norms
  3. Use of aluminum hydroxide antacids (e.g. Maalox® and Mylanta®), systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to the Screening Visit
  4. Current or prior use of leuprorelin (e.g., Lupron®, Viadur®, Eligard®), triptorelin (TRELSTAR®), goserelin (Zoladex®), or other drugs known to delay puberty
  5. Use of growth hormone therapy within 12 months before the Screening Visit
  6. Presence of nephrocalcinosis on renal ultrasound grade 4
  7. Planned or recommended orthopedic surgery, including staples, 8-plates or osteotomy, within the clinical trial period
  8. Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits
  9. Evidence of hyperparathyroidism (PTH levels 2.5X upper limit of normal [ULN])
  10. Use of medication to suppress PTH (e.g., cinacalcet, calcimimetics) within 2 months prior to the Screening Visit
  11. 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.
  12. Presence of a concurrent disease or condition that would interfere with study participation or affect safety
  13. History of recurrent infection or predisposition to infection, or of known immunodeficiency
  14. Use of a therapeutic monoclonal antibody within 90 days prior to the Screening Visit or history of allergic or anaphylactic reactions to any monoclonal antibody
  15. Presence or history of any hypersensitivity to KRN23 excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects.
  16. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02915705

Contacts
Contact: Kimberly Trant 415-483-8125 KTrant@ultragenyx.com

  Hide Study Locations
Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Vanessa Guzman    323-361-8633    vguzman@chla.usc.edu   
Principal Investigator: Pisit Pitkcheewanont         
UCSF Recruiting
San Francisco, California, United States, 94158
Contact: Melissa Fang    415-476-3557    melissa.fang@ucsf.edu   
Principal Investigator: Anthony Portale         
United States, Indiana
Indiana University School of Medicine Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Marian Hart    317-948-8346    marihart@iu.edu   
Principal Investigator: Erik Imel         
United States, Missouri
Shriners Hospital For Children Recruiting
St. Louis, Missouri, United States, 63131
Contact: Eric Cox    314-432-3600 ext 1110    ecox@shrinenet.org   
Principal Investigator: Michael Whyte         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232-9170
Contact: Margo Black    615-343-5846    margo.black@vanderbilt.edu   
Principal Investigator: Jill Simmons         
Australia, New South Wales
Sydney Children's Hospital Network Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Lynne Foxall    61 2 984 53147    LynneF@chw.edu.au   
Principal Investigator: Craig Munns         
Canada, Ontario
Children's Hospital of Eastern Ontario (CHEO) Research Institute Not yet recruiting
Ottowa, Ontario, Canada
Contact: Danielle Cram    613-737-7600 ext 4124    dcram@cheo.on.ca   
Principal Investigator: Leanne Ward, MD         
SickKids Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Holly Tschrihart    416-813-8407    holly.tschirhart@sickkids.ca   
Principal Investigator: Etienne Sochett         
Canada, Quebec
Shriners Hospital for Children - Canada Not yet recruiting
Montreal, Quebec, Canada, H4A 0A9
Contact: Michaela Durigova    514-282-7158    mdurigova@shriners.mcgill.ca   
Principal Investigator: Francis Glorieux         
Denmark
ODense University Hospital Not yet recruiting
Odense C, Denmark, 5000
Contact: Louise Ronning    +45 30493237    Louise.Ronning-Baek@rsyd.dk   
Principal Investigator: Henrik Christesen         
Germany
Children's Hospital University Cologne Not yet recruiting
Cologne, Germany, 50937
Contact: Monika Kron    +49 221 478 84747    monika.kron@uk-koeln.de   
Principal Investigator: Jorg Semler         
Universitaetsklinikum Magdeburg A. oe. R.-Otto-von-Guericke Universty Not yet recruiting
Magdeburg, Germany, 39120
Contact: Susan Empting    +49 221 478 84747    susann.empting@med.ovgu.de   
Principal Investigator: Klaus Mohnike         
Ireland
Children's University Hospital Not yet recruiting
Dublin, Ireland, 1
Contact: Aoife Carey    +353 1 892 1846    aoife.mcarey@cuh.ie   
Principal Investigator: Ciara McDonnell         
Italy
University of Florence Not yet recruiting
Florence, Italy, 50139
Contact: Caterina Fossi    +39 055 7946303    caterina.fossi@unifi.it   
Principal Investigator: Maria Luisa Brandi         
(IRCCS) - Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele) Not yet recruiting
Milan, Italy, 20132
Contact: Jesús Argente    +34 915035915    jesus.argente@fundacionendo.org   
Principal Investigator: Stefano Mora         
IRCCS Istituto Auxologico Italiano Not yet recruiting
Milan, Italy, 20145
Contact: Silvia Vai    +39 02 619112438    s.vai@auxologico.it   
Principal Investigator: Maria Luisa Bianchi         
U.O. Pediatria 1, AOUP Not yet recruiting
Pisa, Italy, 56126
Contact: Giampiero Baroncelli    +39 050 993 168    g.baroncelli@med.unipi.it   
Principal Investigator: Giampiero Baroncelli         
Japan
Aichi Chidren's Medical Center Not yet recruiting
Obu, Aichi, Japan, 474-8710
Contact: Ichi Tobo    81-562-43-0500    shoni-tiken@sk00106.achmc.pref.aichi.jp   
Principal Investigator: Takashi Hamajima         
Hyogo Prefectural Kobe Children's Hospital Recruiting
Kobe, Hyogo, Japan, 654-0047
Contact: Satoshi Kishimoto    81-78-360-1655    kishimoto.satoshi@e-smo.co.jp   
Principal Investigator: Katsumi Goji         
Kanagawa Children's Medical Center Recruiting
Yokohama, Kanagawa, Japan, 232-8555
Principal Investigator: Koji Muroya         
Osaka University Hospital Recruiting
Suita-shi, Osaka, Japan, 565-0871
Principal Investigator: Takuo Kubota         
Okayama Saiseikai General Hospital Recruiting
Okayama, Japan, 700-0013
Principal Investigator: Hiroyuki Tanaka         
Japan Community Healthcare Organization Osaka Hospital Recruiting
Osaka, Japan, 553-0003
Contact: Kunihiko Tanaka    81-6-6441-5451    chiken_soudan@okn.gr.jp   
Principal Investigator: Noriyuki Namba         
National Center for Child Health and Development Recruiting
Tokyo, Japan, 157-8535
Principal Investigator: Reiko Horikawa         
Korea, Republic of
Seoul National University Hospital Not yet recruiting
Seoul, Korea, Republic of, 03080
Contact: YuKyoung Yun    82-10-9168-0875    miso6060@naver.com   
Principal Investigator: Hae II Cheong         
Spain
Hospital Infantil Universitario Niño Jesús Not yet recruiting
Madrid, Spain, 28009
Contact: Silvia Martin    +34 606 968 517    smartinp@salud.madrid.org   
Principal Investigator: Gabriel Martos-Moreno         
Sweden
Karolinska Institutet and University Hospital Not yet recruiting
Stockholm, Sweden, 17176
Contact: Ola Nilsson    +46 8 5177 9710    ola.nilsson@ki.se   
Principal Investigator: Ola Nilsson         
United Kingdom
Birmingham Children's Hospital Not yet recruiting
Birmingham, United Kingdom, B4 6NH
Contact: Claire Smith    +44 121 333 9156    Claire.Harris@bch.nhs.uk   
Principal Investigator: Wolfgang Hogler         
Royal Manchester Children's Hospital - University of Manchester Not yet recruiting
Manchester, United Kingdom, M13 9WL
Contact: Rachel Cox         
Contact    +44 0161 701 1720    Rachel.Cox@cmft.nhs.uk   
Principal Investigator: Raja Padidela         
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Kyowa Hakko Kirin Co., Ltd
  More Information

Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02915705     History of Changes
Other Study ID Numbers: UX023-CL301 
Study First Received: May 23, 2016
Last Updated: January 13, 2017

Additional relevant MeSH terms:
Hypophosphatemia
Familial Hypophosphatemic Rickets
Phosphorus Metabolism Disorders
Metabolic Diseases
Rickets, Hypophosphatemic
Rickets
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Calcium Metabolism Disorders
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamins
Vitamin D
Ergocalciferols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on February 27, 2017