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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 May 2017 by Ultragenyx Pharmaceutical Inc
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc Identifier:
First received: May 23, 2016
Last updated: May 2, 2017
Last verified: May 2017
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: No masking
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


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

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 identifier: NCT02915705

Contact: Patient Advocacy

  Hide Study Locations
United States, California
Children's Hospital Los Angeles Active, not recruiting
Los Angeles, California, United States, 90027
UCSF Active, not recruiting
San Francisco, California, United States, 94158
United States, Indiana
Indiana University School of Medicine Active, not recruiting
Indianapolis, Indiana, United States, 46202
United States, Missouri
Shriners Hospital For Children Active, not recruiting
Saint Louis, Missouri, United States, 63131
United States, Tennessee
Vanderbilt University Medical Center Active, not recruiting
Nashville, Tennessee, United States, 37232-9170
Australia, New South Wales
Sydney Children's Hospital Network Active, not recruiting
Westmead, New South Wales, Australia, 2145
Canada, Ontario
Children's Hospital of Eastern Ontario (CHEO) Research Institute Active, not recruiting
Ottowa, Ontario, Canada
SickKids Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Holly Tschrihart    416-813-8407   
Principal Investigator: Etienne Sochett         
Canada, Quebec
Shriners Hospital for Children - Canada Active, not recruiting
Montreal, Quebec, Canada, H4A 0A9
ODense University Hospital Not yet recruiting
Odense C, Denmark, 5000
Contact: Louise Ronning    +45 30493237   
Principal Investigator: Henrik Christesen         
Children's Hospital University Cologne Not yet recruiting
Cologne, Germany, 50937
Contact: Monika Kron    +49 221 478 84747   
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   
Principal Investigator: Klaus Mohnike         
Children's University Hospital Not yet recruiting
Dublin, Ireland, 1
Contact: Aoife Carey    +353 1 892 1846   
Principal Investigator: Ciara McDonnell         
University of Florence Not yet recruiting
Florence, Italy, 50139
Contact: Caterina Fossi    +39 055 7946303   
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   
Principal Investigator: Stefano Mora         
IRCCS Istituto Auxologico Italiano Not yet recruiting
Milan, Italy, 20145
Contact: Silvia Vai    +39 02 619112438   
Principal Investigator: Maria Luisa Bianchi         
U.O. Pediatria 1, AOUP Not yet recruiting
Pisa, Italy, 56126
Contact: Giampiero Baroncelli    +39 050 993 168   
Principal Investigator: Giampiero Baroncelli         
Aichi Chidren's Medical Center Not yet recruiting
Obu, Aichi, Japan, 474-8710
Contact: Ichi Tobo    81-562-43-0500   
Principal Investigator: Takashi Hamajima         
Hyogo Prefectural Kobe Children's Hospital Active, not recruiting
Kobe, Hyogo, Japan, 654-0047
Kanagawa Children's Medical Center Active, not recruiting
Yokohama, Kanagawa, Japan, 232-8555
Osaka University Hospital Active, not recruiting
Suita-shi, Osaka, Japan, 565-0871
Okayama Saiseikai General Hospital Active, not recruiting
Okayama, Japan, 700-0013
Japan Community Healthcare Organization Osaka Hospital Active, not recruiting
Osaka, Japan, 553-0003
National Center for Child Health and Development Active, not recruiting
Tokyo, Japan, 157-8535
Korea, Republic of
Seoul National University Hospital Active, not recruiting
Seoul, Korea, Republic of, 03080
Hospital Infantil Universitario Niño Jesús Not yet recruiting
Madrid, Spain, 28009
Contact: Silvia Martin    +34 606 968 517   
Principal Investigator: Gabriel Martos-Moreno         
Karolinska Institutet and University Hospital Active, not recruiting
Stockholm, Sweden, 17176
United Kingdom
Birmingham Children's Hospital Active, not recruiting
Birmingham, United Kingdom, B4 6NH
Royal Manchester Children's Hospital - University of Manchester Not yet recruiting
Manchester, United Kingdom, M13 9WL
Contact: Rachel Cox         
Contact    +44 0161 701 1720   
Principal Investigator: Raja Padidela         
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Kyowa Hakko Kirin Co., Ltd
  More Information

Responsible Party: Ultragenyx Pharmaceutical Inc Identifier: NCT02915705     History of Changes
Other Study ID Numbers: UX023-CL301
Study First Received: May 23, 2016
Last Updated: May 2, 2017

Additional relevant MeSH terms:
Familial Hypophosphatemic Rickets
Rickets, Hypophosphatemic
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
Metabolic Diseases
Phosphorus Metabolism Disorders
Vitamin D Deficiency
Deficiency Diseases
Nutrition Disorders
Vitamin D
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents processed this record on May 24, 2017