Effective Dosing of Burosumab in XLH

NCT07183579 | Recruiting

• 2 other identifiers: 25033291899
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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. Prior 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. Burosumab (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/kg per dose. NICE recommends a starting dose of 0.4mg/kg, a normal maintenance dose of 0.8mg/kg and a maximum of 2mg/kg (up to 90mg). The British National Formulary for Children (BNFC) gives the same advice. However, the European Medicines Agency recommends a starting dose of 0.8mg/kg per dose which is, therefore, the standard starting dose now. Some patients achieve symptom and biochemical control on less than 0.8 mg/kg per dose. They may be exposed to higher doses than necessary. To 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. The 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.

Conditions

X-linked Hypophosphatemia (XLH)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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/kg per dose of Burosumab.

  During study period, up to 1 year

Secondary Outcomes (12)

• Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg/kg per dose with those started on a dose of 0.8 mg/kg per dose and above - time to biochemical control

  12 months following first dose of Burosumab

• Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg/kg per dose with those started on a dose of 0.8 mg/kg per dose and above - change in height SDS

  12 months following first dose of Burosumab

• Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg/kg per dose with those started on a dose of 0.8 mg/kg per dose and above - dose difference

  12 months following first dose of Burosumab

• Comparison of outcomes for patients started on Burosumab at a dose of less than 0.8 mg/kg per dose with those started on a dose of 0.8 mg/kg per dose and above - cost difference

  12 months following first dose of Burosumab

• Comparison of patients with a raised baseline PTH (prior to initiation of Burosumab) to those with a normal PTH - dose difference

  12 months following first dose of Burosumab

Study Arms (1)

XLH

Children and young people with XLH treated with Burosumab

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients with XLH treated with Burosumab under the care of participating centres.

You may qualify if:

• A diagnosis of x-linked hypophosphataemia (XLH) including genetic confirmation of a PHEX mutation.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Nottingham: lead
• Nottingham University Hospitals NHS Trust: collaborator
• Birmingham Women's and Children's NHS Foundation Trust: collaborator
• University Hospitals Bristol and Weston NHS Foundation Trust: collaborator
• University Hospital Southampton NHS Foundation Trust: collaborator
• Sheffield Children's NHS Foundation Trust: collaborator
• Manchester University NHS Foundation Trust: collaborator
• Newcastle-upon-Tyne Hospitals NHS Trust: collaborator
• Alder Hey Children's NHS Foundation Trust: collaborator

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

RECRUITING

Related Publications (4)

• Saraff V, Nadar R, Hogler W. New Developments in the Treatment of X-Linked Hypophosphataemia: Implications for Clinical Management. Paediatr Drugs. 2020 Apr;22(2):113-121. doi: 10.1007/s40272-020-00381-8.

  PMID: 31965544 BACKGROUND

• Padidela R, Cheung MS, Saraff V, Dharmaraj P. Clinical guidelines for burosumab in the treatment of XLH in children and adolescents: British paediatric and adolescent bone group recommendations. Endocr Connect. 2020 Oct;9(10):1051-1056. doi: 10.1530/EC-20-0291.

  PMID: 33112809 BACKGROUND

• Imel EA, Glorieux FH, Whyte MP, Munns CF, Ward LM, Nilsson O, Simmons JH, Padidela R, Namba N, Cheong HI, Pitukcheewanont P, Sochett E, Hogler W, Muroya K, Tanaka H, Gottesman GS, Biggin A, Perwad F, Mao M, Chen CY, Skrinar A, San Martin J, Portale AA. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019 Jun 15;393(10189):2416-2427. doi: 10.1016/S0140-6736(19)30654-3. Epub 2019 May 16.

  PMID: 31104833 BACKGROUND

• Carpenter TO, Whyte MP, Imel EA, Boot AM, Hogler W, Linglart A, Padidela R, Van't Hoff W, Mao M, Chen CY, Skrinar A, Kakkis E, San Martin J, Portale AA. Burosumab Therapy in Children with X-Linked Hypophosphatemia. N Engl J Med. 2018 May 24;378(21):1987-1998. doi: 10.1056/NEJMoa1714641.

  PMID: 29791829 BACKGROUND

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets; Hypophosphatemia; Rickets; Bone Diseases, Metabolic; Nephrocalcinosis

Condition Hierarchy (Ancestors)

Rickets, Hypophosphatemic; Bone Diseases; Musculoskeletal Diseases; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Calcinosis

Study Officials

• James Law, BMBS, PhD, MRCPCH

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James M Law, BMBS, PhD, MRCPCH

CONTACT

01159249924; james.law@nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: September 19, 2025
• Study Start: September 8, 2025
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: January 2026 for 7 years
• Access Criteria: The study protocol will be uploaded to the University of Nottingham Research Data Repository and will be publicly available. This study uses pseudonymised clinical data collected as part of routine care from patients with X-linked hypophosphataemia (XLH) across multiple NHS centres. Due to the rarity of XLH and the risk of re-identification, individual participant data (IPD) will not be made publicly available. However, researchers may request access to fully anonymised or aggregated summary data by contacting the Chief Investigator. Requests will be reviewed by the study team and may be granted for appropriate academic or clinical research purposes, subject to a data-sharing agreement and compliance with GDPR and ethical approvals. Access will not be granted to case report forms, or source documentation.

Locations

GB (1)