X-linked Hypophosphatemia (XLH)Phase 1/2NCT04188964
Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Patients Less Than 1 Year of Age
A Phase 1/2 study testing Burosumab in people with X-linked Hypophosphatemia (XLH), run by Kyowa Kirin Pharmaceutical Development Ltd at 9 sites in 6 countries.
Trial summary
A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Paediatric Patients from Birth to Less than 1 Year of Age with X-linked Hypophosphatemia (XLH) Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- X-linked Hypophosphatemia (XLH)
- What is being tested?
- Burosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 9 sitesin 6 countries
- Study dates
- 26 Feb 2020to 6 Mar 2024
- Phase
- Phase 1/2
- 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 Up to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female pediatric subjects, aged <12 months at burosumab treatment initiation.
- Pediatric subjects with PHEX mutation or variant of uncertain significance in either the subject or a directly related family member with appropriate X-linked inheritance.
- Presenting serum phosphate levels below the age-specific LLN at Screening.
- A legally authorized representative has provided written informed consent prior to any research-related procedures.
- A legally authorized representative 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 required by the study protocol, including providing access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history.
Who cannot join
- The pediatric subject's legally authorized representative is unwilling or unable to stop the subject's treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analogue (e.g. calcitriol, alfacalcidol) for at least 1 week before planned treatment start and for the duration of the study.
- Preterm pediatric patients (defined as born before 37 weeks of pregnancy) with a chronological age of <6 months. Enrolment of preterm pediatric patients with a chronological age ≥6 months must be confirmed by the Study Medical Monitor before study entry.
- Impairment of renal function measured as serum creatinine above the age-adjusted normal range and estimated GFR (calculated using the Bedside Schwartz equation) below the age-adjusted normal range.
- Presence of nephrocalcinosis on renal ultrasound.
- Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits.
- Presence of a concurrent disease or condition that would interfere with study participation or affect subject safety.
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- Predisposition to infection or known immunodeficiency.
- Severe dermatological conditions over the available injection sites.
- Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
- Metabolic bone disease, nutritional rickets and/or osteopenia of other origin than XLH at Screening and/or Baseline.
- Serum levels of 25-hydroxyvitamin D (25(OH)D) below the LLN that are clinically significant in the opinion of the Investigator.
- Evidence of any hyperparathyroidism not associated with XLH as determined by the Investigator.
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
United Kingdom3 sites
Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust
London
Great Ormond Street Hospital
London
Royal Manchester Children's Hospital
Manchester
France2 sites
Centre de reference des maladies renales rares-Hospices Civils de Lyon-Hopital Femme Mere Enfant
Lyon
Hopital Kremlin APHP
Paris
About this study
Official title: A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Pediatric Patients From Birth to Less Than 1 Year of Age With X-linked Hypophosphatemia (XLH)
A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Paediatric Patients from Birth to Less than 1 Year of Age with X-linked Hypophosphatemia (XLH)
Read the detailed description
BUR-CL207 is a multicenter, open-label, non-randomized Phase 1/2 study in pediatric patients with XLH initiating treatment with burosumab at <12 months of age. The study includes a total treatment period of up to 48 weeks across 3 cohorts. Subjects will be enrolled in 2 age subgroups: (1) ≥6 months to <12 months of age, and (2) <6 months of age at initiation of burosumab treatment. Cohorts will aim to include 3 subjects per cohort depending on the starting dose of burosumab and relative response of patients to treatment as assessed by serum phosphate levels and by the treating physician (Investigator). Cohorts will commence in a staggered manner starting with Cohort 1, followed by Cohorts 2 and 3, which may start in parallel after an adequate observation period (4 weeks) in Cohort 1 and with approval from the Sponsor's Medical Monitor and the DSMB. The cohorts are defined as follows:
- Cohort 1: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted lower limit of normal [LLN]), and age from ≥6 months to <12 months of age at initiating treatment with burosumab with starting dose of 0.4 mg/kg.
- Cohort 2: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted LLN), and age from ≥6 months to <12 months of age at initiating treatment with burosumab with a starting dose of 0.8 mg/kg (upon Data Safety Monitoring Board [DSMB] confirmation).
- Cohort 3: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted LLN), and <6 months of age at initiating treatment with burosumab with a starting dose of 0.4 mg/kg (upon DSMB confirmation). Following enrollment of the first 3 or 4 subjects in Cohort 3, an interim population PK/PD evaluation may be performed to determine whether the starting dose for the cohort can be increased to 0.8 mg/kg.
- Conditions
- X-linked Hypophosphatemia (XLH)
- 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
Also called KRN23, Crysvita
Burosumab is a sterile clear colourless to slightly yellow and preservative free solution supplied in single use 5ml vials containing 1 mL of Burosumab at a concentration of 10mg/mL,20 mg/mL or 30mg/mL, administered by SC injections every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Pediatric subjects > = 6 months to < 12 months will receive a starting dose of 0.4mg/kg administered subcutaneously (SC) every 2 weeks (Q2W) for 48 weeks with the option of the dose to be increased to 0.8mg/kg upon recommendation of the Data Safety Management Board (DSMB). The dose can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response. Upon recommendation of the DSMB subjects < 6 months can then start at 0.4mg/kg starting dose administered subcutaneously (SC) every 2 weeks (Q2W) for 48 weeks with the option to be increased to 0.8mg/kg upon recommendation of the DSMB and can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response. Receives: Drug: Burosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability of Burosumab in paediatric subjects with X-linked Hypophosphatemia (XLH) starting treatment below 12 months of age
Incidence, frequency, and severity of adverse events (AEs) and serious AEs (SAEs), including clinically significant changes in laboratory, physical examinations, vital signs, ECGs and imaging assessments
Measured: From Baseline to scheduled time points (measured throughout the study up to Week 48).
Secondary outcomes (7)
To characterize the pharmacokinetics (PK) of Burosumab following subcutaneous (SC) injection in paediatric subjects with XLH below 12 months of age.
Burosumab serum concentrations and PK parameters, including apparent clearance (CL/F), apparent volume of distribution (V/F), area under the serum concentration-time curve (AUC), maximum serum drug concentration (Cmax) and other parameters, as appropriate.
Measured: Measured throughout the study up to Week 48
To characterize the effect of Burosumab on serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) in paediatric subjects with XLH starting treatment below 12 months of age
Changes in serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D)
Measured: Change from Baseline at Week 20, 26, 32, 40 and 48
To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Change in serum alkaline phosphatase (ALP).
Measured: Baseline and Week 48
To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Appearance in radiographic appearance of rickets severity as assessed by the Radiograph Global Impression of Change (RGI-C) scoring system.
Measured: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
The appearance in rickets severity assessed by total Rickets Severity Score (RSS).
Measured: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score.
Measured: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Change in recumbent length in cm, height-for-age z-scores, and percentiles.
Measured: At week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2019
- Study start26 Feb 2020
- Primary completion4 Oct 2023
- Study completion6 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for X-linked Hypophosphatemia (XLH)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin Pharmaceutical Development Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04188964
- Sponsor's protocol ID
- BUR-CL207
- Status last verified
- Nov 2024
- First submitted
- 25 Nov 2019
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Linglart A, Emma F, Bacchetta J, de la Cerda F, Hayes W, Cheung M, Cocca A, Hogler W, Padidela R, Henderson L, Tudor A, Okada H, Sun W, Quattrocchi E. Safety, tolerability, pharmacokinetics, and efficacy of burosumab in infants with X-linked hypophosphataemia: an open-label, multicentre, non-randomised study. Lancet Diabetes Endocrinol. 2026 Jun;14(6):475-484. doi: 10.1016/S2213-8587(26)00013-6. Epub 2026 Apr 24.
PubMed 42044650
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Pediatric Patients From Birth to Less Than 1 Year of Age With X-linked Hypophosphatemia (XLH)
- ClinicalTrials.gov ID
- NCT04188964
- Acronym / sponsor ID
- BUR-CL207
- Conditions
- X-linked Hypophosphatemia (XLH)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Kyowa Kirin Pharmaceutical Development LtdIndustry (pharma, biotech, devices)
- Study start
- 26 Feb 2020 (actual)
- Primary completion
- 4 Oct 2023 (actual)
- Study completion
- 6 Mar 2024 (actual)
- First posted
- 6 Dec 2019 (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.
A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Paediatric Patients from Birth to Less than 1 Year of Age with X-linked Hypophosphatemia (XLH)
Detailed description
BUR-CL207 is a multicenter, open-label, non-randomized Phase 1/2 study in pediatric patients with XLH initiating treatment with burosumab at <12 months of age. The study includes a total treatment period of up to 48 weeks across 3 cohorts. Subjects will be enrolled in 2 age subgroups: (1) ≥6 months to <12 months of age, and (2) <6 months of age at initiation of burosumab treatment. Cohorts will aim to include 3 subjects per cohort depending on the starting dose of burosumab and relative response of patients to treatment as assessed by serum phosphate levels and by the treating physician (Investigator). Cohorts will commence in a staggered manner starting with Cohort 1, followed by Cohorts 2 and 3, which may start in parallel after an adequate observation period (4 weeks) in Cohort 1 and with approval from the Sponsor's Medical Monitor and the DSMB. The cohorts are defined as follows:
- Cohort 1: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted lower limit of normal [LLN]), and age from ≥6 months to <12 months of age at initiating treatment with burosumab with starting dose of 0.4 mg/kg.
- Cohort 2: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted LLN), and age from ≥6 months to <12 months of age at initiating treatment with burosumab with a starting dose of 0.8 mg/kg (upon Data Safety Monitoring Board [DSMB] confirmation).
- Cohort 3: pediatric subjects with XLH and hypophosphatemia (serum phosphate below the age-adjusted LLN), and <6 months of age at initiating treatment with burosumab with a starting dose of 0.4 mg/kg (upon DSMB confirmation). Following enrollment of the first 3 or 4 subjects in Cohort 3, an interim population PK/PD evaluation may be performed to determine whether the starting dose for the cohort can be increased to 0.8 mg/kg.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: BurosumabPediatric subjects > = 6 months to < 12 months will receive a starting dose of 0.4mg/kg administered subcutaneously (SC) every 2 weeks (Q2W) for 48 weeks with the option of the dose to be increased to 0.8mg/kg upon recommendation of the Data Safety Management Board (DSMB). The dose can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response. Upon recommendation of the DSMB subjects < 6 months can then start at 0.4mg/kg starting dose administered subcutaneously (SC) every 2 weeks (Q2W) for 48 weeks with the option to be increased to 0.8mg/kg upon recommendation of the DSMB and can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response. |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Male or female pediatric subjects, aged <12 months at burosumab treatment initiation.
- Pediatric subjects with PHEX mutation or variant of uncertain significance in either the subject or a directly related family member with appropriate X-linked inheritance.
- Presenting serum phosphate levels below the age-specific LLN at Screening.
- A legally authorized representative has provided written informed consent prior to any research-related procedures.
- A legally authorized representative 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 required by the study protocol, including providing access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history.
Key exclusion criteria (12 listed)
- The pediatric subject's legally authorized representative is unwilling or unable to stop the subject's treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analogue (e.g. calcitriol, alfacalcidol) for at least 1 week before planned treatment start and for the duration of the study.
- Preterm pediatric patients (defined as born before 37 weeks of pregnancy) with a chronological age of <6 months. Enrolment of preterm pediatric patients with a chronological age ≥6 months must be confirmed by the Study Medical Monitor before study entry.
- Impairment of renal function measured as serum creatinine above the age-adjusted normal range and estimated GFR (calculated using the Bedside Schwartz equation) below the age-adjusted normal range.
- Presence of nephrocalcinosis on renal ultrasound.
- Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits.
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 |
|---|---|---|
| BurosumabAlso: KRN23, CrysvitaBurosumab is a sterile clear colourless to slightly yellow and preservative free solution supplied in single use 5ml vials containing 1 mL of Burosumab at a concentration of 10mg/mL,20 mg/mL or 30mg/mL, administered by SC injections every 2 weeks. | Drug | Treatment |
Primary outcome
To assess the safety and tolerability of Burosumab in paediatric subjects with X-linked Hypophosphatemia (XLH) starting treatment below 12 months of age
Time frame: From Baseline to scheduled time points (measured throughout the study up to Week 48).
Incidence, frequency, and severity of adverse events (AEs) and serious AEs (SAEs), including clinically significant changes in laboratory, physical examinations, vital signs, ECGs and imaging assessments
7 secondary outcomes
To characterize the pharmacokinetics (PK) of Burosumab following subcutaneous (SC) injection in paediatric subjects with XLH below 12 months of age.
Time frame: Measured throughout the study up to Week 48
To characterize the effect of Burosumab on serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) in paediatric subjects with XLH starting treatment below 12 months of age
Time frame: Change from Baseline at Week 20, 26, 32, 40 and 48
To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Time frame: Baseline and Week 48
To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Time frame: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Time frame: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Time frame: At week 48
To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities
Time frame: At week 48
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 7 Nov 2024.
- Derived from this study: PubMed 42044650Linglart A, Emma F, Bacchetta J, de la Cerda F, Hayes W, Cheung M, Cocca A, Hogler W, Padidela R, Henderson L, Tudor A, Okada H, Sun W, Quattrocchi E. Safety, tolerability, pharmacokinetics, and efficacy of burosumab in infants with X-linked hypophosphataemia: an open-label, multicentre, non-randomised study. Lancet Diabetes Endocrinol. 2026 Jun;14(6):475-484. doi: 10.1016/S2213-8587(26)00013-6. Epub 2026 Apr 24.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Burosumab in people with X-linked Hypophosphatemia (XLH), run by Kyowa Kirin Pharmaceutical Development Ltd at 9 sites in 6 countries.
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 5 inclusion and 12 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 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom, France, Austria, Italy, Spain and 1 more country. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
To assess the safety and tolerability of Burosumab in paediatric subjects with X-linked Hypophosphatemia (XLH) starting treatment below 12 months of age (time frame: From Baseline to scheduled time points (measured throughout the study up to Week 48).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04188964, which also lists 1 linked publication.
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 7 Nov 2024.