ESPE Abstracts (2021) 94 P2-98

ESPE2021 ePoster Category 2 Bone, growth plate and mineral metabolism (41 abstracts)

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.

Raja Padidela 1 , Moira Cheung 2 , Jeremy Allgrove 3 , Justine Bacchetta 4 , Oliver Semler 5 , Angela Heubner 6 , Dirk Schnabel 7 , Franceso Emma 8 , Ola Nilsson 9 , Wolfgang Högler 10 , Francisco De La Cerda Ojeda 11 , Emilia Quattrocchi 12 & Agnes Linglart 13

1Royal Manchester Children’s Hospital and Faculty of Biology, Manchester, United Kingdom; 2Evelina London Children’s Hospital, London, United Kingdom; 3Great Ormond Street Hospital, London, United Kingdom; 4Hospices Civils de Lyon-Hopital Femme Mere Enfant, Lyon, France; 5Children’s Hospital University, Cologne, Germany; 6Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany; 7Pediatric Endocrinology, Charite, Berlin, Germany; 8Bambino Gesù Children’s Hospital – IRCCS, Rome, Italy; 9Astrid Lindgrens Barnsjukhus, Karolinska Universitetssjukhuset and Örebro Universitet, Stockholm, Sweden; 10Kepler University Hospital and Johannes Kepler University Linz, Linz, Austria; 11Hospital Virgen del Rocío, Seville, Spain; 12Kyowa Kirin Pharmaceutical Development Ltd, Galashiels, United Kingdom; 13AP-HP University Bicêtre Paris Saclay, Paris, France

Background: X-linked hypophosphatemia (XLH) is caused by mutations in PHEX which increases serum Fibroblast Growth Factor 23 (FGF23) concentrations leading to phosphate wasting 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). Burosumab is licensed by the European Medicines Agency for management 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 approximately 20 XLH infants (<12 months old) with a confirmed PHEX mutation. Baseline fasted serum phosphate below the age-adjusted normal range is required for inclusion. Infants receiving conventional therapy will discontinue medications >1 week before commencing 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 number per cohort will depend on age of eligible patients as enrolled). Burosumab dose adjustments will be determined by serum phosphate 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 burosumab 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 characterizing the immunogenicity of burosumab following administration to pediatric subjects with XLH. BUR-CL207 is conducted in Austria, France, Germany, Italy, Spain, Sweden, UK. EudraCT: 2019-000469-19

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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