A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Paediatric Patients from Birth to Less than 1 Year of Age with X-linked Hypophosphatemia (XLH)
BUR-CL207 is a multicenter, open-label, non-randomized Phase 1/2 study in pediatric patients with XLH initiating treatment with burosumab at \<12 months of age. The study includes a total treatment period of up to 48 weeks across 3 cohorts. Subjects will be enrolled in 2 age subgroups: (1) ≥6 months to \<12 months of age, and (2) \<6 months of age at initiation of burosumab treatment. Cohorts will aim to include 3 subjects per cohort depending on the starting dose of burosumab and relative response of patients to treatment as assessed by serum phosphate levels and by the treating physician (Investigator). Cohorts will commence in a staggered manner starting with Cohort 1, followed by Cohorts 2 and 3, which may start in parallel after an adequate observation period (4 weeks) in Cohort 1 and with approval from the Sponsor's Medical Monitor and the DSMB. The cohorts are defined as follows: * Cohort 1: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted lower limit of normal \[LLN\]), and age from ≥6 months to \<12 months of age at initiating treatment with burosumab with starting dose of 0.4 mg/kg. * Cohort 2: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted LLN), and age from ≥6 months to \<12 months of age at initiating treatment with burosumab with a starting dose of 0.8 mg/kg (upon Data Safety Monitoring Board \[DSMB\] confirmation). * Cohort 3: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted LLN), and \<6 months of age at initiating treatment with burosumab with a starting dose of 0.4 mg/kg (upon DSMB confirmation). Following enrollment of the first 3 or 4 subjects in Cohort 3, an interim population PK/PD evaluation may be performed to determine whether the starting dose for the cohort can be increased to 0.8 mg/kg.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Burosumab is a sterile clear colourless to slightly yellow and preservative free solution supplied in single use 5ml vials containing 1 mL of Burosumab at a concentration of 10mg/mL,20 mg/mL or 30mg/mL, administered by SC injections every 2 weeks.
Kepler Universitaetsklinikum GmbH
Linz, Austria
Centre de reference des maladies renales rares-Hospices Civils de Lyon-Hopital Femme Mere Enfant
Lyon, France
Hopital Kremlin APHP
Paris, France
Ospedale Pediatrico Bambino Gesù
To assess the safety and tolerability of Burosumab in paediatric subjects with X-linked Hypophosphatemia (XLH) starting treatment below 12 months of age
Incidence, frequency, and severity of adverse events (AEs) and serious AEs (SAEs), including clinically significant changes in laboratory, physical examinations, vital signs, ECGs and imaging assessments
Time frame: From Baseline to scheduled time points (measured throughout the study up to Week 48).
To characterize the pharmacokinetics (PK) of Burosumab following subcutaneous (SC) injection in paediatric subjects with XLH below 12 months of age.
Burosumab serum concentrations and PK parameters, including apparent clearance (CL/F), apparent volume of distribution (V/F), area under the serum concentration-time curve (AUC), maximum serum drug concentration (Cmax) and other parameters, as appropriate.
Time frame: Measured throughout the study up to Week 48
To characterize the effect of Burosumab on serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) in paediatric subjects with XLH starting treatment below 12 months of age
Changes in serum phosphate and 1,25-dihydroxyvitamin D (1,25\[OH\]2D)
Time frame: Change from Baseline at Week 20, 26, 32, 40 and 48
To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Change in serum alkaline phosphatase (ALP).
Time frame: Baseline and Week 48
To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Appearance in radiographic appearance of rickets severity as assessed by the Radiograph Global Impression of Change (RGI-C) scoring system.
Time frame: At week 48
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Rome, Italy
Hospital Virgen del Rocío
Seville, Spain
Karolinska University Hospital
Stockholm, Sweden
Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust
London, United Kingdom
Great Ormond Street Hospital
London, United Kingdom
Royal Manchester Children's Hospital
Manchester, United Kingdom
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
The appearance in rickets severity assessed by total Rickets Severity Score (RSS).
Time frame: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score.
Time frame: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Change in recumbent length in cm, height-for-age z-scores, and percentiles.
Time frame: At week 48