efficacy and safety of burosumab versus oral phosphate and active vitamin d treatment in pediatric patients with xlh

Conditions: X-Linked Hypophosphatemia

Summary: the primary objective of this study is to evaluate the effect of krn23 (burosumab) therapy in improving rickets in children with xlh compared with active control (oral phosphate/active vitamin d).


Eligibility criteria:
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 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