Study of the Anti-FGF23 Antibody, Burosumab, in Adults With XLH

NCT03920072 | Completed Phase 3 FDA Drug

• 1 other identifier: BUR02
• Study Type: interventional
• Target: 35
• Locations: 4 countries
• Sites: 10

Brief Summary

This is phase 3b open-label, international, multicenter study to continue to monitor the long-term safety and efficacy of burosumab in adult patients with XLH that participated in previous clinical trials with burosumab (UX023-CL303 / UX023-CL304).

Conditions

X-linked Hypophosphatemia

Keywords

Crysvita; Burosumab; X-linked Hypophosphatemia (XLH); PHEX Gene Mutation; PHEXdb

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects achieving mean serum phosphorus levels above the LLN (2.5mg/dL[0.81mmol/L]), as averaged across dose cycles between baseline and their last administered dose.

  To establish the effect of burosumab treatment on maintaining serum phosphorus levels to within normal range in adults with XLH.

  Serum phosphorous levels will be monitored from Screening and every 12 weeks until the end of the study, at approximately 144 weeks.

Secondary Outcomes (12)

• Effect of burosumab on pre-existing pseudofracture healing will be monitored by centrally read targeted X-Ray

  Targetted X-Rays at ongoing fracture sites will be taken at the End of Study Visit, approximately week 144.

• Effect of burosumab on patients walking ability measured using the 6 Minute Walk Test.

  The 6MWT will be measured at Baseline and then every 12 weeks for the first 48 weeks and then every 24 weeks for up to 144 weeks

• Effect of burosumab on Patient mobility assessed using the Timed Up and Go Test (TUG).

  The TUG Test will be assessed at Baseline and then every 12 weeks for the first 48 weeks and then every 24 weeks for up to 144 weeks

• Effect of burosumab on stiffness and physical function will be assessed using WOMAC.

  The WOMAC questionnaire will be administered at Baseline and then every 12 weeks for 48 weeks and every 12 weeks for up to 48 weeks and then every 24 weeks for up to 96 weeks

• Effect of burosumab on patient's pain severity and the impact of pain on functioning will be assessed using the Short-form Brief Pain Inventory questionnaire.

  The BPI will be administered at Baseline and then every 12 weeks for 48 weeks and then every 24 weeks for up to 144 weeks

Study Arms (1)

Open label

OTHER

All subjects will be administered subcutaneously burosumab every 4 weeks at the dosage defined in study UX023-CL303 or UX023-CL304 until December 2021 or when the drug becomes commercially available.

Drug: Burosumab

Interventions

Burosumab DRUG

Burosumab is a sterile, clear, colourless and preservative free solution supplied in single-use 5ml vials containing 1mL of burosumab at a concentration of 30mg/mL

Also known as: KRN23, Crysvita

Open label

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures.
• Subjects who participated in Study UX023-CL303 or UX023-CL304. Any subjects that did not complete Study UX023-CL303 or UX023-CL304 may be included on a case-by-case basis. Subjects' enrolment is not dependent on any response to Primary or Secondary endpoints in studies UX023-CL303 or UX023-CL304.
• Willing to provide access to prior medical records for the collection of historical growth, biochemical and radiographic data, and disease history.
• Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments.
• Females of child-bearing potential must have a negative urine pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not to be of child-bearing potential include those who have been in menopause for at least two years prior to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total hysterectomy or bilateral salpingo-oophorectomy. If sexually active, male and female subjects must be willing to use one highly effective method of contraception for the duration of the study.

You may not qualify if:

• Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits and deemed as clinically significant in the opinion of the investigator.
• Presence of a concurrent disease or condition that would interfere with study participation or affect safety in the opinion of the investigator or Sponsor.
• Use of any investigational product other than burosumab or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• Subjects with major protocol deviations in Study UX023-CL303 or UX023-CL304 which in the view of the investigator places the subject at high risk of poor treatment compliance or of not completing the study.
• Subjects who discontinued treatment from Study UX023-CL303 or UX023-CL304 due to either a grade ≥3 treatment-related hypersensitivity reaction or a burosumab-related hypersensitivity reaction reported as a SAE.

Sponsors & Collaborators

• Kyowa Kirin Pharmaceutical Development Ltd: lead

Study Sites (10)

CHU de Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Hopital Cochin

Paris, 75014, France

Location

St. Vincent's University Hospital

Dublin, D04 T6F4, Ireland

Location

Azienda ospedaliera universitaria Careggi

Florence, 50139, Italy

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

National Hospital for Neurology and Neurosurgery-University College London Hospitals NHS Foundation Trust

London, WC1N 3BG, United Kingdom

Location

Nuffield Orthopaedic Centre - Oxford University Hospitals Nhs Trust

Oxford, OX3 7LD, United Kingdom

Location

Northen General Hospital

Sheffield, S5 7AU, United Kingdom

Location

Royal National Orthopaedic Hospital NHS Trust

Stanmore, HA7 4LP, United Kingdom

Location

Related Publications (1)

• Kamenicky P, Briot K, Brandi ML, Cohen-Solal M, Crowley RK, Keen R, Kolta S, Lachmann RH, Lecoq AL, Ralston SH, Walsh JS, Rylands AJ, Williams A, Sun W, Nixon A, Nixon M, Javaid MK. Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment. RMD Open. 2023 Feb;9(1):e002676. doi: 10.1136/rmdopen-2022-002676.

  PMID: 36854566 DERIVED

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets

Interventions

burosumab

Condition Hierarchy (Ancestors)

Rickets, Hypophosphatemic; Rickets; Bone Diseases, Metabolic; 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; Hypophosphatemia; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Study Officials

• Peter Kamenicky

  CHU de Bicêtre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, international, multicenter

Study Record Dates

• First Submitted: October 29, 2018
• First Posted: April 18, 2019
• Study Start: March 7, 2019
• Primary Completion: April 7, 2022
• Study Completion: April 7, 2022
• Last Updated: May 20, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); IT (1); IE (1); GB (5)