X-linked Hypophosphatemia (XLH) MedDRA version: 20.0 Level: LLT Classification code 10016206 Term: Familial hypophosphataemic rickets System Organ Class: 100000004850
Conditions
Interventions
Trade Name: CRYSVITA
Product Name: burosumab
Product Code: KRN23
Pharmaceutical Form: Solution for injection
INN or Proposed INN: BUROSUMAB
Current Sponsor code: KRN23
Other descriptive name: FGF23
Co
Sponsors
Kyowa Kirin Pharmaceutical Development Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female pediatric subjects, aged =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The pediatric subject’s legally authorized representative is unwilling or unable to stop the subject’s treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analogue (e.g. calcitriol, alfacalcidol) for at least 1 week before planned treatment start and for the duration of the study. 2. Preterm pediatric patients (defined as born before 37 weeks of pregnancy) with a chronological age of <6 months. Enrolment of preterm pediatric patients with a chronological age =6 months must be confirmed by the Study Medical Monitor before study entry. 3. Impairment of renal function measured as serum creatinine above the age-adjusted normal range and estimated GFR (calculated using the Bedside Schwartz equation) below the age-adjusted normal range. 4. Presence of nephrocalcinosis on renal ultrasound 5. Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits. 6. Presence of a concurrent disease or condition that would interfere with study participation or affect subject safety. 7. Predisposition to infection or known immunodeficiency. 8. Severe dermatological conditions over the available injection sites. 9. 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. 10. Metabolic bone disease, nutritional rickets and/or osteopenia of other origin than XLH at screening and/or baseline 11. Serum Levels of 25-hydroxyvitamin D (25(OH)D) below the LLN that are clinically significant in the opinion of the investigator 12 Evidence of hyperthyroidism not associated with XLH as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of burosumab in pediatric subjects with X-linked Hypophosphatemia (XLH) starting treatment below 12 months of age with up to 48 weeks of exposure.;Secondary Objective: • To characterize the effect of burosumab on serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) in pediatric subjects with XLH starting treatment below 12 month of age. • To characterize the pharmacokinetics (PK) of burosumab following subcutaneous (SC) injection in pediatric subjects with XLH below 12 months of age. • To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities. ;Primary end point(s): Incidence, frequency, and severity of AEs and SAEs, including clinically significant changes in laboratory and imaging assessments, from Baseline to scheduled time points (measured throughout the study up to Week 48). ;Timepoint(s) of evaluation of this end point: Baseline to Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacodynamic (PD) Change from Baseline over time (Week 20, 32, 40 and 48) in: • serum phosphate, • 1,25(OH) 2 D. Pharmacokinetic (PK) Burosumab serum concentrations and PK parameters, including CL/F, V/F, AUC, C max and other parameters, as appropriate, following SC administration. Efficacy • Change from Baseline over time and at Week 48 in serum ALP. • Change from Baseline or from time of appearance in radiographic appearance of rickets severity as assessed by the RGI-C scoring system at Week 48. • Change from Baseline or from time of appearance in rickets severity assessed by total RSS at Week 48. • Change from Baseline in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score at Week 48. • Change from Baseline in recumbent length at Week 48 in cm, height-for-age z-scores, and percentiles.;Timepoint(s) of evaluation of this end point: PD Baseline and Weeks 20, 26, 32, 40 and 48. PK Screening, Baseline and Weeks 2, 4, 6, 8, 12, 13, 16, 20, 26, 32, 40, 48 and follow-up/end of study visit Week 56. Efficacy Baseline (or from time of appearance) to Week 48. | — |
Countries
Austria, France, Germany, Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Group
Kyowa Kirin Pharmaceutical Development Ltd.
Outcome results
None listed