Anti-FGF23 (Burosumab) in Adult Patients With XLH (BurGER)

May 2, 2023 updated by: Wuerzburg University Hospital

An Investigator-sponsored Phase 3b Open-label Study of Anti- FGF23 Antibody Burosumab (KRN23) in Adult Patients With Xlinked Hypophosphatemia (XLH) in GERmany - BurGER

X-linked hypophosphatemia (XLH) rare genetic disorder due by inactivating mutations in the PHEX gene leading to increased levels in FGF-23. Elevated FGF-23 reduces renal phosphate reabsorbtion and and limits 1-alpha hydroxylase driven Vitamin D activation, eventually leading to phosphate wasting, defective bone mineralization and additional health issues.

Burosumab is a recombinant fully human IgG1 monoclonal antibody developed to treat XLH by binding FGF23, thereby restoring normal phosphate homeostasis.

BUR03 is a Phase 3b open-label, single-arm, single-center study to confirm the efficacy and safety of Burosumab treatment in adult (age ≥18 years) XLH patients without upper age limit and irrespective of baseline pain level and to further evaluate the efficacy in this cohort and the assocaited effect of treatment on physical functioning, mobility and activity.

The study aims at enrolling and treating 34 subjects with a confirmed diagnosis of XLH with q4w s.c. injection of Burosumab 1mg/kg body weight over 48 weeks.

Primary objective is to attiain normal serum phosphorus levels, secondary objectives include key parameters of physical function and activity, mobility and mineral homeostasis.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Würzburg, Germany, 97074
        • Clinical Trial Unit, Orthopedic Department, Wuerzburg University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female, aged ≥ 18 years, inclusive
  • Diagnosis of X-linked Hypophosphatemia supported by classic clinical features of adult XLH (e.g. short statue or bowed legs, clinical symptoms as judged by the investigator) and at least one of the following at Screening visit:

    • documented PHEX mutation in either the patient, or
    • in a directly related family member with appropriate X-linked inheritance
    • Increased serum levels of c-term FGF23 or iFGF23
  • Biochemical findings consistent with XLH at Screening visit following overnight fasting:

    • Serum phosphorus level or
    • TmP/GFR below lab specific lower limit of normal (LLN)
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration equitation) or eGFR of 30 up to 60 mL/min at Screening visit with confirmation that the renal insufficiency is not due to nephrocalcinosis
  • Subjects who provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures.
  • Participants 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 2 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.
  • Female Participants of child-bearing potential who are sexually active must consent to use an effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine devices, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence) from the period following the signing of the informed consent through 12 weeks after the last dose of study drug.

Exclusion Criteria:

  • 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.
  • Vitamin D deficiency (25OH D3 < 20ng/ml); if Vitamin D is low at screening, substitution is allowed and recompensation has to be confirmed before treatment start by normalized levels of Vitamin D (25OH D3 ≥ 20ng/ml)
  • Serum intact parathyroid hormone (iPTH) >2.5-fold the upper limit of normal (ULN)
  • Severe renal insufficiency with a Glomerular filtration rate (eGFR) <30 at screening
  • Treatment with oral phosphate and / or active vitamin D analogues in addition to Burosumab treatment. (In order to ensure appropriate patient care and preclude any harm due to deficient supply, required supplementation with oral phosphate salts and/or active vitamin D analogues at screening can be continued during the run-in phase but has to be stopped before Baseline and Initiation of treatment with Burosumab.)
  • Treatment with bisphosphates or Denosumab within the last 6 months
  • Treatment with Teriparatide within the last 3 months
  • Intake of calcimimetics within 30 days before screening
  • Patients with known hypersensitivity to Burosumab and the active substances of any of the excipients of Burosumab
  • Presence of a concurrent disease or condition that would interfere with study participation or affect safety in the opinion of the investigator
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Open label Burosumab
Burosumab Q4W, 1mg/kg body weight s.c.
Q4w, 1mg/kg Body weight, s.c.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of Burosumab treatment on attaining serum phosphorus levels within the normal range in adults with XLH
Time Frame: 48 weeks
Proportion of subjects attaining a serum phosphorus concentration within the normal range
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in chari rise test completion time
Time Frame: 48 weeks
Change in chair rise test completion time from baseline to end of study visit
48 weeks
Change in 6-Minute-Walk test
Time Frame: 48 weeks
Change in 6-Minute-Walk test distance from baseline to end of study visit
48 weeks
Change in timed up-and down stairs completion time
Time Frame: 48 weeks
Change in timed up-and down stairs completion time from baseline to end of study visit
48 weeks
Normalization of TmP/GFR
Time Frame: 48 weeks
Normalization of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR), proportion of subjects achieving normal values
48 weeks
Activity tracking
Time Frame: 48 weeks
Activity tracking using 'Actibelt', to delineate total hours of physical activity per week
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Lothar Seefried, MD, University Hospital Wuerzburg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 7, 2021

Primary Completion (Actual)

March 17, 2023

Study Completion (Actual)

March 17, 2023

Study Registration Dates

First Submitted

December 22, 2020

First Submitted That Met QC Criteria

January 4, 2021

First Posted (Actual)

January 5, 2021

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

May 2, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Only aggregated, analyzed participant data will be shared

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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