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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02915705




Registration number
NCT02915705
Ethics application status
Date submitted
23/05/2016
Date registered
27/09/2016
Date last updated
29/08/2024

Titles & IDs
Public title
Efficacy and Safety of Burosumab Versus Oral Phosphate and Active Vitamin D Treatment in Pediatric Patients With XLH
Scientific 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)
Secondary ID [1] 0 0
UX023-CL301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
X-Linked Hypophosphatemia 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Other - burosumab
Treatment: Drugs - Oral Phosphate Supplement
Treatment: Drugs - active vitamin D

Experimental: Burosumab - Burosumab 0.8 mg/kg starting dose, administered Q2W by SC injection during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants continued to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.

Active comparator: Active Control - Multiple daily doses of oral phosphate and one or more daily doses of active vitamin D therapy, titrated and individualized by the investigator based on published recommendations during the Treatment Period (up to Week 64). During the Treatment Extension Period (Week 64 to Week 140), participants crossed over to receive a starting dose of SC burosumab 0.8 mg/kg Q2W. Participants in Japan and Korea did not enter the Treatment Extension Period.


Treatment: Other: burosumab
solution for subcutaneous (SC) injection

Treatment: Drugs: Oral Phosphate Supplement
oral tablet; oral solution; oral powder

Treatment: Drugs: active vitamin D
tablet, oral solution

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Radiographic Global Impression of Change (RGI-C) Global Score at Week 40
Timepoint [1] 0 0
Week 40
Secondary outcome [1] 0 0
Percentage of Participants With a Mean RGI-C Global Score = +2.0 (Responders) at Week 40
Timepoint [1] 0 0
Week 40
Secondary outcome [2] 0 0
Percentage of Participants With a Mean RGI-C Global Score = +2.0 (Responders) at Week 64
Timepoint [2] 0 0
Week 64
Secondary outcome [3] 0 0
RGI-C Global Score at Week 64
Timepoint [3] 0 0
Week 64
Secondary outcome [4] 0 0
Change From Baseline in RSS Total Score at Week 40
Timepoint [4] 0 0
Baseline, Week 40
Secondary outcome [5] 0 0
Change From Baseline in RSS Total Score at Week 64
Timepoint [5] 0 0
Baseline, Week 64
Secondary outcome [6] 0 0
RGI-C Long Leg Score at Week 40
Timepoint [6] 0 0
Week 40
Secondary outcome [7] 0 0
RGI-C Long Leg Score at Week 64
Timepoint [7] 0 0
Week 64
Secondary outcome [8] 0 0
Change From Baseline in Height-For-Age Z-Scores to Week 40
Timepoint [8] 0 0
Baseline, Week 40
Secondary outcome [9] 0 0
Change From Baseline in Height-For-Age Z-Scores to Week 64
Timepoint [9] 0 0
Baseline, Week 64
Secondary outcome [10] 0 0
Change in Growth Velocity Z Score From Baseline to Week 40
Timepoint [10] 0 0
Baseline, Week 40
Secondary outcome [11] 0 0
Change in Growth Velocity Z Score From Baseline to Week 64
Timepoint [11] 0 0
Baseline, Week 64
Secondary outcome [12] 0 0
Change From Baseline Over Time in Serum Phosphorus Concentration, up to Week 64
Timepoint [12] 0 0
Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64
Secondary outcome [13] 0 0
Change From Baseline Over Time in Serum Phosphorus Concentration, Weeks 66-112
Timepoint [13] 0 0
Baseline, Weeks 66, 68, 76, 88, 100, 112
Secondary outcome [14] 0 0
Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 64
Timepoint [14] 0 0
Baseline, Weeks 1, 4, 8, 16, 24, 32, 40, 52, 64
Secondary outcome [15] 0 0
Change From Baseline in Mean Post-Baseline Serum Phosphorus Level to Week 140 (During Treatment With Burosumab)
Timepoint [15] 0 0
Burosumab arm: Baseline, Week 1, 4, 8, 16, 24, 32, 40, 52, 64, 66, 68, 76, 88, 100, 112, 124, 140; Active Control arm: Baseline, Week 68, 76, 88, 100, 112, 124, 140
Secondary outcome [16] 0 0
Percentage of Participants Reaching the Normal Range of Serum Phosphorus Concentration (3.2 - 6.1 mg/dL)
Timepoint [16] 0 0
Burosumab arm: Baseline, up to Week 140; Active Control arm: Baseline, Week 68 up to Week 140
Secondary outcome [17] 0 0
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, up to Week 64
Timepoint [17] 0 0
Baseline, Weeks 1, 2, 4, 8, 12, 16, 24, 32, 33, 40, 52, 64
Secondary outcome [18] 0 0
Change From Baseline Over Time in 1,25-Dihydroxyvitamin D, Weeks 68 to 112
Timepoint [18] 0 0
Baseline, Weeks 68, 76, 88, 100, 112
Secondary outcome [19] 0 0
Change From Baseline Over Time in TmP/GFR, up to Week 64
Timepoint [19] 0 0
Baseline, Weeks 4, 8, 16, 24, 32, 40, 52, 64
Secondary outcome [20] 0 0
Change From Baseline Over Time in TmP/GFR, Week 68 to 112
Timepoint [20] 0 0
Baseline, Weeks 68, 76, 88, 112
Secondary outcome [21] 0 0
Change From Baseline Over Time in Serum ALP, up to Week 64
Timepoint [21] 0 0
Baseline, Weeks 16, 24, 40, 52, 64
Secondary outcome [22] 0 0
Change From Baseline Over Time in Serum ALP, Week 68 to 112
Timepoint [22] 0 0
Baseline, Weeks 68, 76, 88, 100, 112
Secondary outcome [23] 0 0
Percent Change From Baseline Over Time in Serum ALP, up to Week 112
Timepoint [23] 0 0
Baseline, Weeks 16, 24, 40, 52, 64, 68, 76, 88, 100, 112
Secondary outcome [24] 0 0
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants = 5 Years of Age at the Screening Visit) at Week 40
Timepoint [24] 0 0
Baseline, Week 40
Secondary outcome [25] 0 0
Change From Baseline in the PROMIS Pediatric Pain Interference, Physical Function Mobility and Fatigue Domain Scores (For Participants = 5 Years of Age at the Screening Visit) at Week 64
Timepoint [25] 0 0
Baseline, Week 64
Secondary outcome [26] 0 0
Change From Baseline in the FPS-R (For Participants = 5 Years of Age at the Screening Visit) at Week 40
Timepoint [26] 0 0
Baseline, Week 40
Secondary outcome [27] 0 0
Change From Baseline in the FPS-R (For Participants = 5 Years of Age at the Screening Visit) at Week 64
Timepoint [27] 0 0
Baseline, Week 64
Secondary outcome [28] 0 0
Change From Baseline in the 6MWT Total Distance at Week 40
Timepoint [28] 0 0
Baseline, Week 40
Secondary outcome [29] 0 0
Change From Baseline in the 6MWT Total Distance at Week 64
Timepoint [29] 0 0
Baseline, Week 64
Secondary outcome [30] 0 0
Percent of Predicted Normal in the 6MWT Total Distance at Week 40
Timepoint [30] 0 0
Baseline, Week 40
Secondary outcome [31] 0 0
Percent of Predicted Normal in the 6MWT Total Distance at Week 64
Timepoint [31] 0 0
Baseline, Week 64

Eligibility
Key inclusion criteria
1. Male or female, aged 1 to =12 years with radiographic evidence of rickets as determined by central readers
2. Phosphate-regulating endopeptidase homolog, X-linked (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 below the age-adjusted upper limit of normal
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) 7 days prior to the Randomization 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. Female subjects of childbearing potential must be willing to use a highly effective method of contraception for the duration of the study plus 12 weeks after stopping the study drug. Sexually active male subjects with female partners of childbearing potential must consent to use a condom with spermicide or a highly effective method of contraception for the duration of the study plus 12 weeks after stopping the study drug
Minimum age
1 Year
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Tanner stage 4 or higher in any of the following: genitals, breast, or pubic hair, based on physical examination
2. Height percentile > 50th based on country-specific norms
3. Use of aluminum hydroxide antacids (eg, Maalox® and Mylanta®), systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to the Screening Visit
4. Current or prior use of leuprorelin (eg, 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 orthopedic surgery, including osteotomy or implantation or removal of staples, 8 plates, or any other hardware, within the first 40 weeks of the study
8. Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits
9. Evidence of hyperparathyroidism (parathyroid hormone [PTH] levels 2.5X upper limit of normal [ULN])
10. Use of medication to suppress PTH (eg, 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. OR, in Japan, use of any investigational product or investigational medical device within 4 months prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Japan
State/province [7] 0 0
Kanagawa
Country [8] 0 0
Japan
State/province [8] 0 0
Okayama
Country [9] 0 0
Japan
State/province [9] 0 0
Osaka
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Sweden
State/province [11] 0 0
Stockholm
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Birmingham
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kyowa Kirin, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Kyowa Kirin Co., Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Ultragenyx Pharmaceutical Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.