BUR-CL207 : An Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Pediatric Patients from Birth to Less than 1 Year of Age with XLH

• Background: X-linked hypophosphatemia (XLH) is caused by mutations in PHEX which increases serum Fibroblast Growth Factor 23 (FGF23) concentrations leading to phosphate wast-ing and osteomalacia. Burosumab is a recombinant fully human IgG1 monoclonal antibody which selectively inhibits the activity of FGF23. In clinical trials burosumab demonstrated significant clinical improvements in radiological rickets severity, growth, and biochemistry among XLH children aged 1-12 years compared to those continuing on conventional therapy (Imel 2019). Buro-sumab is licensed by the European Medicines Agency for manage-ment of XLH in children >1 year. Early initiation of treatment in XLH improves height (Makitie 2003) and effective and sustained treatment improves dental and musculoskeletal outcomes. Study BUR-CL207 has been designed to evaluate the safety, tolerability, pharmacology and efficacy of burosumab in pediatric patients <12 months.Methods: This study is enrolling and will include approxi-mately 20 XLH infants (<12 months old) with a confirmed PHEXmutation. Baseline fasted serum phosphate below the age-adjusted normal range is required for inclusion. Infants receiving conven-tional therapy will discontinue medications >1 week before com-mencing burosumab treatment and for the duration of study. This study comprises three cohorts with a total treatment period of up to 48 weeks. Subjects will be enrolled into a cohort dependent on their age. Cohorts 1 and 2 for subjects aged: ≥6 months to <12 months, and cohort 3 for subjects <6 months. Burosumab starting doses of 0.4 mg/kg (Cohorts 1 and 3) and 0.8 mg/kg (Cohort 2), administered every two weeks, will be studied in each subgroup in a staggered manner with up to 3 subjects per cohort (final num-ber per cohort will depend on age of eligible patients as enrolled). Burosumab dose adjustments will be determined by serum phos-phate levels. A Data Safety Monitoring Board will review data accrued in each cohort.Outcome Measurements: The primary endpoint is the safety of burosumab in pediatric patients <12 months. The secondary endpoints include: PK assessments and change from baseline in serum phosphate and 1,25(OH)2D, the clinical effects of buro-sumab on growth and prevention and/or healing of rickets and skeletal deformities. Exploratory endpoints include presence and appearance of bone and skeletal XLH related abnormalities in pediatric subjects starting treatment <12 months, anthropometric and motor development in pediatric subjects with XLH and char-acterizing the immunogenicity of burosumab following adminis-tration to pediatric subjects with XLH.BUR-CL207 is conducted in Austria, France, Germany, Italy, Spain, Sweden, UK.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Pediatrik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Pediatrics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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