[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100607055":3},{"organization":4,"outcomesModule":7,"designInfo":52,"detailedDescription":55,"studyPopulation":56,"armGroups":57,"interventions":11,"overallOfficials":61,"centralContacts":65,"locations":72,"responsibleParty":90,"collaborators":92,"id":109,"slug":11,"hasResults":110,"nctId":111,"briefTitle":112,"officialTitle":113,"acronym":11,"eligibilityCriteria":114,"healthyVolunteers":110,"sex":115,"minAge":116,"maxAge":117,"enrollmentInfo":118,"targetDuration":11,"studyType":121,"phases":11,"briefSummary":122,"conditions":123,"keywords":125,"overallStatus":75,"whyStopped":11,"lastUpdateSubmitDate":151,"lastUpdatePostDateStruct":152,"startDateStruct":155,"completionDateStruct":157,"leadSponsor":159,"locationsCount":160},{"fullName":5,"class":6},"University of Nottingham","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":11},[9],{"measure":10,"description":11,"timeFrame":12},"The proportion of patients who achieved biochemical control (serum phosphate above the lower limit of the local reference range) on a dose of less than 0.8 mg\u002Fkg per dose of Burosumab.",null,"During study period, up to 1 year",[14,18,21,24,27,30,33,35,39,43,46,49],{"measure":15,"description":16,"timeFrame":17},"Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg\u002Fkg per dose with those started on a dose of 0.8 mg\u002Fkg per dose and above - time to biochemical control","• Mean difference in time to achieve biochemical control (serum phosphate above the lower limit of the local reference range).","12 months following first dose of Burosumab",{"measure":19,"description":20,"timeFrame":17},"Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg\u002Fkg per dose with those started on a dose of 0.8 mg\u002Fkg per dose and above - change in height SDS","• Mean difference in change in height SDS after 12 months of treatment.",{"measure":22,"description":23,"timeFrame":17},"Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg\u002Fkg per dose with those started on a dose of 0.8 mg\u002Fkg per dose and above - dose difference","• Mean difference in dose of Burosumab at 12 months after first dose.",{"measure":25,"description":26,"timeFrame":17},"Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg\u002Fkg per dose with those started on a dose of 0.8 mg\u002Fkg per dose and above - cost difference","• Mean difference in cost of giving Burosumab.",{"measure":28,"description":29,"timeFrame":17},"Comparison of patients with a raised baseline PTH (prior to initiation of Burosumab) to those with a normal PTH - dose difference","• Mean difference in dose of Burosumab required to achieve biochemical control (serum phosphate above the lower limit of the local reference range).",{"measure":31,"description":32,"timeFrame":17},"Comparison of patients with a raised baseline PTH (prior to initiation of Burosumab) to those with a normal PTH - time to control","• Mean difference in time to achieve biochemical control.",{"measure":34,"description":20,"timeFrame":17},"Comparison of patients with a raised baseline PTH (prior to initiation of Burosumab) to those with a normal PTH - change in height SDS",{"measure":36,"description":37,"timeFrame":38},"Factors influencing dosing regimen in patients on Burosumab","Analysis using model comparison (additive and subtractive ANOVA models) to assess the association between initial Burosumab dose (mg\u002Fkg per dose) and the following patient-related factors:\n\n1. Calendar year of Burosumab initiation\n2. Age at treatment initiation (years)\n3. Time from diagnosis of XLH to Burosumab initiation (months)\n4. Duration of prior conventional treatment (months)\n\nEach factor will be included in models predicting Burosumab dose (mg\u002Fkg per dose). The relative importance of each predictor will be determined through model fit statistics (e.g., AIC, adjusted R²).","At baseline, first dose of Burosumab",{"measure":40,"description":41,"timeFrame":42},"Description of progression and monitoring following the initiation of Burosumab - PTH","• Description of baseline PTH (low, normal, high) and change following treatment (stable, temporary fall, persistent fall, temporary rise, persistent rise).","From first dose of Burosumab to 12 months later",{"measure":44,"description":45,"timeFrame":42},"Description of progression and monitoring following the initiation of Burosumab - nephrocalcinosis","• Proportion of patients with new\u002Fdeterioration in nephrocalcinosis.",{"measure":47,"description":48,"timeFrame":42},"Description of progression and monitoring following the initiation of Burosumab - urinary calcium & phosphate","• Mean change in urinary calcium and phosphate excretion.",{"measure":50,"description":51,"timeFrame":42},"Description of progression and monitoring following the initiation of Burosumab - adverse events","• Qualitative description of other reported adverse effects.",{"allocation":11,"interventionModel":11,"interventionModelDescription":11,"primaryPurpose":11,"observationalModel":53,"timePerspective":54,"maskingInfo":11},"COHORT","RETROSPECTIVE","X-linked hypophosphatemia (XLH) is a rare, lifelong genetic disorder caused by inactivating mutations in the PHEX gene, leading to elevated levels of fibroblast growth factor 23 (FGF23), which induces renal phosphate wasting. The resultant hypophosphataemia disrupts bone mineralisation, causing rickets, skeletal deformities, growth failure, and chronic pain.\n\nHistorically, treatment has relied on oral phosphate and activated vitamin D analogues, which are burdensome and only partially effective. Burosumab (Crysvita), a monoclonal antibody that targets and neutralizes FGF23, is a transformative therapy for XLH. It has been shown to normalise serum phosphate levels, improve growth parameters, and reduce rickets severity. However, real-world data on optimal dosing regimens remain limited.\n\nThis study is a multi-centre, pragmatic, retrospective observational analysis conducted across paediatric metabolic bone centres in England. The objective is to assess whether a starting dose of less than 0.8 mg\u002Fkg of Burosumab is effective in achieving biochemical control and to characterise dosing variation and outcomes across centres. The current standard dose recommended by the European Medicines Agency (EMA) is 0.8 mg\u002Fkg every two weeks, but clinical experience and historical trial data suggest that a proportion of patients may achieve biochemical control on lower doses.\n\nThis study will review data from paediatric patients with a diagnosis of XLH who have received at least 12 months of continuous Burosumab treatment under paediatric dosing criteria. Patients will be included regardless of whether they subsequently transitioned to adult dosing, provided their data under paediatric treatment can be clearly delineated.\n\nData will be extracted from existing clinical records by each participating centre. These records form part of routine care and include biochemistry (serum phosphate, calcium, alkaline phosphatase, creatinine, parathyroid hormone; and urinary calcium, phosphate, and creatinine), auxology (height, weight, sitting height), treatment timelines, imaging findings (notably nephrocalcinosis), and documented adverse effects. Data will be submitted in pseudonymised form through a secure portal hosted by the University of Nottingham.\n\nData Quality and Registry Procedures:\n\nA data dictionary has been developed to define all collected variables, including normal ranges and units, and to standardise input across sites.\n\nData validation and consistency checks will be performed at the time of upload, using range and logic rules.\n\nWhere needed, study investigators may request clarification or source verification from submitting centres for apparent anomalies or missing data.\n\nAll data will be stored on encrypted and access-controlled servers. Backups are performed daily, and all transmissions are encrypted.\n\nData will be reviewed centrally, and queries raised where missing, inconsistent, or out-of-window data are identified.\n\nA formal statistical analysis plan has been developed. It includes descriptive analyses (means, medians, ranges, and SDs), between-group comparisons using parametric or non-parametric tests as appropriate, and subgroup analyses based on starting dose, PTH status, and age at treatment initiation.\n\nNo direct patient contact is involved. Ethical approval will be obtained and, in accordance with UK Health Research Authority guidance and GDPR, individual consent is not required because the study uses fully pseudonymised data collected as part of usual care.\n\nSample size justification: A minimum of 35 patients started on less than 0.8 mg\u002Fkg is required to ensure that the 95% confidence interval for the estimated proportion achieving biochemical control does not cross zero, based on a conservative effect estimate of 10%. Inclusion of additional patients treated at or above 0.8 mg\u002Fkg enables robust secondary and comparative analyses.\n\nMissing data strategy: Where values are not available for key time points, interpolation from adjacent data will be used when possible (e.g., to estimate a 6-month height using 3- and 9-month values).\n\nThe study is being coordinated by the University of Nottingham and led by Dr James Law Honorary Clinical Associate Professor and Dr Pooja Sachdev, Clinical Associate Professor in Paediatric Endocrinology and Diabetes. Collaborators include national experts in metabolic bone disease. No external funding has been received; centres are contributing data using existing staff and infrastructure.\n\nThis study aims to improve understanding of the real-world use of Burosumab and support optimisation of dosing strategies to ensure effective, safe, and cost-conscious care for children with XLH.","Patients with XLH treated with Burosumab under the care of participating centres.",[58],{"label":59,"type":11,"description":60,"interventionNames":11},"XLH","Children and young people with XLH treated with Burosumab",[62],{"name":63,"affiliation":5,"role":64},"James Law, BMBS, PhD, MRCPCH","PRINCIPAL_INVESTIGATOR",[66],{"name":67,"role":68,"phone":69,"phoneExt":70,"email":71},"James M Law, BMBS, PhD, MRCPCH","CONTACT","01159249924","82336","james.law@nottingham.ac.uk",[73],{"facility":74,"status":75,"city":76,"state":11,"zip":77,"country":78,"countryCode":79,"cosmosGeoPoint":80,"geoPoint":85,"contacts":86},"Nottingham University Hospitals NHS Trust","RECRUITING","Nottingham","NG7 2UH","United Kingdom","UK",{"type":81,"coordinates":82},"Point",[83,84],-1.15047,52.9536,{"lat":84,"lon":83},[87],{"name":88,"role":68,"phone":11,"phoneExt":11,"email":89},"Pooja Sachdev","pooja.sachdev@nhs.net",{"type":91,"investigatorFullName":11,"investigatorTitle":11,"investigatorAffiliation":11,"oldNameTitle":11,"oldOrganization":11},"SPONSOR",[93,94,96,98,100,102,105,107],{"name":74,"class":6},{"name":95,"class":6},"Birmingham Women's and Children's NHS Foundation Trust",{"name":97,"class":6},"University Hospitals Bristol and Weston NHS Foundation Trust",{"name":99,"class":6},"University Hospital Southampton NHS Foundation Trust",{"name":101,"class":6},"Sheffield Children's NHS Foundation Trust",{"name":103,"class":104},"Manchester University NHS Foundation Trust","OTHER_GOV",{"name":106,"class":6},"Newcastle-upon-Tyne Hospitals NHS Trust",{"name":108,"class":6},"Alder Hey Children's NHS Foundation Trust","100607055",false,"NCT07183579","Effective Dosing of Burosumab in XLH","A Retrospective Observational Study of the Effect of Dosing Regimen of Burosumab on Biochemical Control of Serum Phosphate Levels in Patients With X-linked Hypophosphataemia (XLH)","Inclusion Criteria:\n\n* A diagnosis of x-linked hypophosphataemia (XLH) including genetic confirmation of a PHEX mutation.\n* Has received at least 12 months of continuous Burosumab treatment under paediatric criteria (given Burosumab is not started till a child is 12 months old in England, the minimum age will, therefore, be 2 years old) prior to their 18th birthday.\n\nExclusion Criteria:\n\n* Burosumab received under adult criteria (patients who have received both Burosumab under paediatric arrangements and, subsequently, adult arrangements, can have data obtained during paediatric dosing included).","ALL","2 Years","18 Years",{"count":119,"type":120},120,"ESTIMATED","OBSERVATIONAL","X-linked hypophosphataemia (XLH) is a rare, hereditary condition. The genetic defect leads to low blood phosphate levels and vitamin D suppression. Phosphate is required for strong bones and teeth and to store energy in cells. Low phosphate leads to soft bones (rickets). Patients experience bowed legs, short stature, bone pain and dental pain.\n\nPrior to Burosumab, conventional treatment of XLH previously consisted of two medications. On this regimen, patients take oral phosphate supplements 4-6 times a day and an active form of vitamin D daily. This treatment can leave patients with residual symptoms. They report significant disabilities and reduced quality of life.\n\nBurosumab (Crysvita, Kyowa Kirin) is now the standard paediatric treatment for XLH. It is given once a fortnight by injection under the skin. Early studies used a starting dose of 0.4mg\u002Fkg per dose. NICE recommends a starting dose of 0.4mg\u002Fkg, a normal maintenance dose of 0.8mg\u002Fkg and a maximum of 2mg\u002Fkg (up to 90mg). The British National Formulary for Children (BNFC) gives the same advice.\n\nHowever, the European Medicines Agency recommends a starting dose of 0.8mg\u002Fkg per dose which is, therefore, the standard starting dose now. Some patients achieve symptom and biochemical control on less than 0.8 mg\u002Fkg per dose. They may be exposed to higher doses than necessary.\n\nTo date, approximately 200 patients have started on Burosumab in England. They are all managed by specialist centres. The rare status of XLH means there are relatively few patients in each centre. Treatment effects and trends can only be described by collating data from multiple centres.\n\nThe investigators will undertake a review across multiple English centres of the doses of Burosumab. The review will only collect data already in the patients' health records. It will look at factors affecting the starting dose. The investigators will assess the association between dose, blood markers and growth.",[124],"X-linked Hypophosphatemia (XLH)",[126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150],"Hypophosphatemia, X-Linked Dominant","Rickets","Burosumab","Monoclonal Antibodies","Alkaline Phosphatase","Parathyroid Hormone","Retrospective Studies","Observational Study","Multicenter Study","Dose-Response Relationship, Drug","Child","Adolescent","Pediatrics","X-Linked Hypophosphatemia (XLH)","Metabolic Bone Disease","Crysvita","FGF23 Antibody","Real-World Evidence","Pragmatic Clinical Study","Serum Phosphate","Nephrocalcinosis","Paediatric Endocrinology","Treatment Outcome","Adverse Events","Drug Administration Schedule","2026-05-05",{"date":153,"type":154},"2026-05-11","ACTUAL",{"date":156,"type":154},"2025-11-03",{"date":158,"type":120},"2026-07-01",{"name":5,"class":6},1]