X-linked HypophosphatemiaPhase 3BurGERNCT04695860
Anti-FGF23 (Burosumab) in Adult Patients With XLH
A Phase 3 study testing Burosumab in people with X-linked Hypophosphatemia, run by Wuerzburg University Hospital at 1 site in Germany.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- X-linked Hypophosphatemia
- What is being tested?
- Burosumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteGermany
- Study dates
- 7 Jan 2021to 17 Mar 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Clinical Trial Unit, Orthopedic Department, Wuerzburg University
Würzburg, 97074
About this study
Official title: 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.
Read more
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.
- Conditions
- X-linked Hypophosphatemia
- Being tested
- Burosumab
- Medical subject headings
- Familial Hypophosphatemic Rickets
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BurosumabDrug
Q4w, 1mg/kg Body weight, s.c.
| Study group | Role | What they receive |
|---|---|---|
| Open label Burosumab | Experimental | Burosumab Q4W, 1mg/kg body weight s.c. Receives: Drug: Burosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of Burosumab treatment on attaining serum phosphorus levels within the normal range in adults with XLH
Proportion of subjects attaining a serum phosphorus concentration within the normal range
Measured: 48 weeks
Secondary outcomes (5)
Change in chari rise test completion time
Change in chair rise test completion time from baseline to end of study visit
Measured: 48 weeks
Change in 6-Minute-Walk test
Change in 6-Minute-Walk test distance from baseline to end of study visit
Measured: 48 weeks
Change in timed up-and down stairs completion time
Change in timed up-and down stairs completion time from baseline to end of study visit
Measured: 48 weeks
Normalization of TmP/GFR
Normalization of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR), proportion of subjects achieving normal values
Measured: 48 weeks
Activity tracking
Activity tracking using 'Actibelt', to delineate total hours of physical activity per week
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2021
- Study start7 Jan 2021
- Primary completion17 Mar 2023
- Study completion17 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for X-linked HypophosphatemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Kyowa Kirin, Inc.
- Responsible party
- Sponsor
- Investigators
- Lothar Seefried, MD, Principal investigator, Wuerzburg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04695860
- Sponsor's protocol ID
- BUR03
- Acronym
- BurGER
- Status last verified
- May 2023
- First submitted
- 22 Dec 2020
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Only aggregated, analyzed participant data will be shared
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-sponsored Phase 3b Open-label Study of Anti- FGF23 Antibody Burosumab (KRN23) in Adult Patients With Xlinked Hypophosphatemia (XLH) in GERmany - BurGER
- ClinicalTrials.gov ID
- NCT04695860
- Acronym / sponsor ID
- BurGER / BUR03
- Conditions
- X-linked Hypophosphatemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Collaborators
- Kyowa Kirin, Inc.
- Study start
- 7 Jan 2021 (actual)
- Primary completion
- 17 Mar 2023 (actual)
- Study completion
- 17 Mar 2023 (actual)
- First posted
- 5 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label Burosumab | Experimental | Drug: BurosumabBurosumab Q4W, 1mg/kg body weight s.c. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- Biochemical findings consistent with XLH at Screening visit following overnight fasting:
- 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.
Key exclusion criteria (11 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BurosumabQ4w, 1mg/kg Body weight, s.c. | Drug | Open label Burosumab |
Primary outcome
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
5 secondary outcomes
Change in chari rise test completion time
Time frame: 48 weeks
Change in 6-Minute-Walk test
Time frame: 48 weeks
Change in timed up-and down stairs completion time
Time frame: 48 weeks
Normalization of TmP/GFR
Time frame: 48 weeks
Activity tracking
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Individual participant dataSharing planned: No. Only aggregated, analyzed participant data will be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lothar Seefried, MD principal investigator
Wuerzburg University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Burosumab in people with X-linked Hypophosphatemia, run by Wuerzburg University Hospital at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of Burosumab treatment on attaining serum phosphorus levels within the normal range in adults with XLH (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023; AzTrials last refreshed its copy on 8 Nov 2026.