XLH is a rare, genetic disorder that is serious, chronically debilitating and represents an unmet medical need. This genetic deficiency is estimated to occur in about 1:20,000 live births (Burnett et al. 1964), (Imel et al. 2005). XLH is the most common inherited form of rickets and the most common inherited defect in renal tubular phosphate transport. XLH is transmitted as an X-linked dominant disorder (Dixon et al. 1998). MedDRA version: 20.0 Level: LLT Classification code 10016206 Term: Fami
Conditions
Interventions
Trade Name: CRYSVITA
Product Name: recombinant human igG1
Product Code: KRN23
Pharmaceutical Form: Solution for injection
INN or Proposed INN: BUROSUMAB
Current Sponsor code: KRN23
Other descriptive
Sponsors
Kyowa Kirin Pharmaceutical Development Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Criteria for Inclusion: 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: Main Criteria for Exclusion: 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. Nutritional rickets and/or osteopenia to include exclusion of patients with metabolic bone disease of other origin than XLH at Screening and/or Baseline.
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 64 weeks of exposure.;Secondary Objective: Secondary Objectives: • To characterize the effect of burosumab on serum phosphate, 1,25-dihydroxyvitamin D (1,25[OH] 2 D), and other pharmacodynamic (PD) markers of phosphate homeostasis in pediatric subjects with XLH starting treatment below 12 months 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. Exploratory Objectives: • To evaluate presence and appearance of bone and skeletal XLH related abnormalities in pediatric subjects starting treatment below 12 months of age. • To evaluate anthropometric and motor development in pediatric subjects with XLH. • To characterize the immunogenicity of burosumab following administration to pediatric subjects with XLH.;Primary end point(s): Primary Endpoints: • 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 64). ;Timepoint(s) of evaluation of this end point: Even evaluation times to week 64/ followup week 70 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from Baseline over time (Week 20, 32, 40, 48, 56 and 64) in: • serum phosphate, • 1,25(OH) 2 D. Burosumab serum concentrations and PK parameters, including CL/F, V/F, AUC, C max and other parameters, as appropriate, following SC administration. Spot urine collection was added for measurement of calcium, creatinine, calcium/creatinine ratio, phosphate and ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) at baseline, week 2, week 6, week 20, week 48 and week 64. Change from Baseline over time and at Week 40 and 64 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 40 and 64. • Change from Baseline or from time of appearance in rickets severity assessed by total RSS at Week 40 and 64. • 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 40 and 64. • Change from Baseline in recumbent length at Week 40 and Week 64 in cm, height-for-age z- scores, and percentiles.;Timepoint(s) of evaluation of this end point: Change from Baseline over time (Week 20, 32, 40, 48, 56 and 64) in: • serum phosphate, • 1,25(OH) 2 D. Change from Baseline over time and at Week 40 and 64 in serum ALP. • Change from Baseline or from time of appearance in radiographic appearance of rickets severity as assessed by the RGI-C Spot urine -baseline, week 2, week 6, week 20, week 48 and week 64. scoring system at Week 40 and 64. • Change from Baseline or from time of appearance in rickets severity assessed by total RSS at Week 40 and 64. • Change from Baseline in lower extremity skeletal abnormalities, as determined by the RGI-C long leg score at Week 40 and 64. • Change from Baseline in recumbent length at Week 40 and Week 64 in cm, height-for-age z- scores, and p | — |
Countries
Austria, France, Germany, Italy, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Icon Clinical Research Ltd
Outcome results
None listed