Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS)Early Phase 1NCT03993821
Burosumab for CSHS
A Early Phase 1 study testing Burosumab in people with Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS) and Epidermal Nevus Syndrome, run by Laura Tosi at 1 site in United States.
Trial summary
Burosumab (also known as the drug, Crysvita®) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS), Epidermal Nevus Syndrome
- 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
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2019to 3 Mar 2026
- Phase
- Early Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Patient has confirmed CSHS by physician diagnosis
- Patient has confirmed FGF23 elevations in the context of a low fasting serum phosphorous < 2.5 mg/dL
- Patient able to tolerate burosumab treatment
- Have a corrected serum calcium level < 10.8 mg/dL
- Have an eGFR >25 mL/min/1.73m2 (using CKD-EPI equation)
Show all 10Show fewer
- Must be willing in the opinion of the investigators, to comply with study procedures and schedule
- Provide written informed consent by the subject or a Legal Authorized Representative (LAR) after the study has been explained and prior to any research related procedures begin
- Must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study.
- Must be willing to use a highly effective method of contraception for the duration of the study and for at least 12 weeks after the last dose of the study drug. Highly effective methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (e.g., oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (e.g., oral, injectable, implantable), intrauterine device (IUD) or intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, or sexual abstinence (i.e., refraining from heterosexual intercourse during the entire period of risk associated with the study treatments, when this is in line with the preferred and usual lifestyle of the subject)
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Concomitant use of active vitamin D (i.e. calcitriol) and/or exogenous phosphate supplementation during burosumab therapy. Subjects will be allowed over the counter Vitamin D should levels drop below <20 ng/ml
- Blood phosphorus level within or above the normal range while not taking phosphate or active Vitamin D.
- Severe renal impairment or end-stage renal disease, defined as an eGFR of less than 25 ml/min/1.73m2
- The use or enrollment in studies using other investigational therapies including other monoclonal antibodies
- Subject or Legally Authorized Representative not willing or not able to give written informed consent
Show all 9Show fewer
- In the investigator's opinion, the subject may not be able to meet all the requirements for study participation
- History of hypersensitivity to burosumab excipients that in the opinion of the investigator, places the subject at an increased risk of adverse effects
- Subject has a condition that in the opinion of the investigator could present a concern for subject safety or data interpretation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's National Hospital
Washington D.C., District of Columbia, 20010
About this study
Official title: An Open Label Trial to Assess the Safety and Efficacy of Burosumab in a Single Patient With Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS)
Burosumab (also known as the drug, Crysvita®) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. This drug is already approved for use in patients with X-linked hypophosphatemia (XLH), but not for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS). It is hypothesized that burosumab may provide clinical benefit to a patient with CSHS due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
Read the detailed description
There are multiple disorders (each with a unique underlying cause) that result in unusually high circulating levels of FGF23, which in turn result in renal phosphate wasting and reduced (or aberrantly normal in relationship to elevated FGF23) levels of 1,25-dihydroxy vitamin D (1,25[OH]2D). Across these disorders the clinical symptoms are similar and often include osteomalacia (and, in children, rickets), muscle weakness, fatigue, bone pain, and fractures. Burosumab has been FDA-approved for one of these disorders, X-linked hypophosphatemia (XLH). In single- and repeat-dose clinical studies in subjects with XLH, subcutaneous (SC) administration of burosumab consistently increased and sustained serum phosphorus levels and tubular reabsorption of phosphate (TRP) and improved radiologic rickets, without a major impact on urine calcium levels. Positive results were also observed in a nonclinical pharmacology model of XLH. It is hypothesized that burosumab may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
- Being tested
- Burosumab
- Keywords
- CSHS, Cutaneous Skeletal Hypophosphatemia Syndrome, Epidermal Nevus Syndrome
- Medical subject headings
- Nevus, Sebaceous of Jadassohn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BurosumabDrug
Also called Crysvita
Burosumab, the investigational product, is a recombinant human IgG1 monoclonal antibody targeting FGF23. It is supplied as a sterile, clear, colorless and preservative-free solution and is administered via subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| Burosumab | Experimental | Burosumab, which is FDA-approved for X-linked hypophosphatemic rickets, will be given monthly, for a total of 12 months and titrated to achieve a target fasting serum phosphorus level within normal range for age. The chosen starting dose of burosumab will be 0.3 mg/kg given SQ Q4W. The maximum dose allowed in this protocol is 2.0 mg/kg. Burosumab will be administered via subcutaneous (SC) route. Receives: Drug: Burosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Phosphorus change
Change from baseline over 52 weeks in serum phosphorus with burosumab treatment.
Measured: 52 weeks
Secondary outcomes (13)
Changes in 1,25(OH)2-Vitamin D
Changes from baseline over 52 weeks in 1,25(OH)2-Vitamin D
Measured: 52 weeks
Changes in tubular reabsorption of phosphate (TRP)
Changes from baseline over 52 weeks in tubular reabsorption of phosphate (TRP)
Measured: 52 weeks
Changes in TmP/GFR (the ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate
Changes from baseline over 52 weeks in TmP/GFR (the ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate
Measured: 52 weeks
Biomechanical Marker
Effect of burosumab over 52 weeks on biochemical marker of bone turnover that reflects osteomalacia severity: alkaline phosphatase (ALP).
Measured: 52 weeks
6-minute walk test
Change in walking capacity over 52 weeks as assessed by 6-Minute Walk Test (6MWT)
Measured: 52 weeks
Sit-to-Stand test (STST)
Change in proximal muscle function over 52 weeks as assessed by the Sit-to-Stand test (STST)
Measured: 2 weeks
Brief Pain Inventory (BPI)
Change in Patient/parent-Reported Outcomes over 52 weeks as assessed by Brief Pain Inventory (BPI)
Measured: 52 weeks
Brief Fatigue Inventory (BFI)
Change in Patient/parent-Reported Outcomes over 52 weeks as assessed by Brief Fatigue Inventory (BFI)
Measured: 52 weeks
SF36 item short health survey (SF-36)
Change in Patient/parent-Reported Outcomes over 52 weeks as assessed by SF36 item short health survey (SF-36)
Measured: 52 weeks
PROMIS Pain Intensity
Change in Patient/parent-Reported Outcomes over 52 weeks as assessed by PROMIS Pain Intensity instrument. Pain is rated on a scale of 0-10 where 0 represents no pain and 10 represents the worst possible pain.
Measured: 52 weeks
PROMIS Pain Interference
Change in Patient/parent-Reported Outcomes over 52 weeks as assessed by PROMIS Pain Interference instrument. Responses are aggregated and converted to a T-score from 0-100 where 50 is the mean and every 10 is one standard deviation from the mean.
Measured: 52 weeks
PROMIS Physical Function with Mobility Aid
Change in Patient/parent-Reported Outcomes over 52 weeks as assessed by PROMIS Physical Function with Mobility Aid instrument. Responses are aggregated and converted to a T-score from 0-100 where 50 is the mean and every 10 is one standard deviation from the mean.
Measured: 52 weeks
PROMIS Fatigue
Change in Patient/parent-Reported Outcomes over 52 weeks as assessed by PROMIS Fatigue instrument. Responses are aggregated and converted to a T-score from 0-100 where 50 is the mean and every 10 is one standard deviation from the mean.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start1 Jul 2019
- Primary completion30 Oct 2022
- Study completion3 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS)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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open-label, 52-week study designed to assess the efficacy, safety and pharmacodynamics (PD) of burosumab in a single subject with cutaneous skeletal hypophosphatemia syndrome (CSHS). Burosumab (formerly KRN23) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. It is hypothesized that burosumab may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with X-linked hypophosphatemia (in whom burosumab is FDA-approved) - abnormally elevated FGF23, in the context of low age-adjusted serum phosphorous levels. Patient will be seen at Screening, Baseline and every 2-4 wks, as described in "Schedule of Activities"
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laura Tosi
- Sponsor type
- University, hospital or other
- Collaborators
- Children's National Research Institute, Ultragenyx Pharmaceutical Inc
- Responsible party
- Sponsor-investigator, Laura Tosi, Children's National Research Institute
- Investigators
- Laura Tosi, MD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03993821
- Sponsor's protocol ID
- IRB 11746
- Status last verified
- Jan 2026
- First submitted
- 13 Feb 2019
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Trial to Assess the Safety and Efficacy of Burosumab in a Single Patient With Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS)
- ClinicalTrials.gov ID
- NCT03993821
- Acronym / sponsor ID
- IRB 11746
- Keywords
- CSHS, Cutaneous Skeletal Hypophosphatemia Syndrome, Epidermal Nevus Syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Laura TosiUniversity, hospital or other
- Collaborators
- Children's National Research Institute, Ultragenyx Pharmaceutical Inc
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 30 Oct 2022 (actual)
- Study completion
- 3 Mar 2026 (actual)
- First posted
- 21 Jun 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.
Burosumab (also known as the drug, Crysvita®) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. This drug is already approved for use in patients with X-linked hypophosphatemia (XLH), but not for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS). It is hypothesized that burosumab may provide clinical benefit to a patient with CSHS due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
Detailed description
There are multiple disorders (each with a unique underlying cause) that result in unusually high circulating levels of FGF23, which in turn result in renal phosphate wasting and reduced (or aberrantly normal in relationship to elevated FGF23) levels of 1,25-dihydroxy vitamin D (1,25[OH]2D). Across these disorders the clinical symptoms are similar and often include osteomalacia (and, in children, rickets), muscle weakness, fatigue, bone pain, and fractures. Burosumab has been FDA-approved for one of these disorders, X-linked hypophosphatemia (XLH). In single- and repeat-dose clinical studies in subjects with XLH, subcutaneous (SC) administration of burosumab consistently increased and sustained serum phosphorus levels and tubular reabsorption of phosphate (TRP) and improved radiologic rickets, without a major impact on urine calcium levels. Positive results were also observed in a nonclinical pharmacology model of XLH. It is hypothesized that burosumab may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open-label, 52-week study designed to assess the efficacy, safety and pharmacodynamics (PD) of burosumab in a single subject with cutaneous skeletal hypophosphatemia syndrome (CSHS). Burosumab (formerly KRN23) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. It is hypothesized that burosumab may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with X-linked hypophosphatemia (in whom burosumab is FDA-approved) - abnormally elevated FGF23, in the context of low age-adjusted serum phosphorous levels. Patient will be seen at Screening, Baseline and every 2-4 wks, as described in "Schedule of Activities"
| Arm | Type | Receives |
|---|---|---|
| Burosumab | Experimental | Drug: BurosumabBurosumab, which is FDA-approved for X-linked hypophosphatemic rickets, will be given monthly, for a total of 12 months and titrated to achieve a target fasting serum phosphorus level within normal range for age. The chosen starting dose of burosumab will be 0.3 mg/kg given SQ Q4W. The maximum dose allowed in this protocol is 2.0 mg/kg. Burosumab will be administered via subcutaneous (SC) route. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Patient has confirmed CSHS by physician diagnosis
- Patient has confirmed FGF23 elevations in the context of a low fasting serum phosphorous < 2.5 mg/dL
- Patient able to tolerate burosumab treatment
- Have a corrected serum calcium level < 10.8 mg/dL
Key exclusion criteria (9 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Concomitant use of active vitamin D (i.e. calcitriol) and/or exogenous phosphate supplementation during burosumab therapy. Subjects will be allowed over the counter Vitamin D should levels drop below <20 ng/ml
- Blood phosphorus level within or above the normal range while not taking phosphate or active Vitamin D.
- Severe renal impairment or end-stage renal disease, defined as an eGFR of less than 25 ml/min/1.73m2
- The use or enrollment in studies using other investigational therapies including other monoclonal antibodies
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: CrysvitaBurosumab, the investigational product, is a recombinant human IgG1 monoclonal antibody targeting FGF23. It is supplied as a sterile, clear, colorless and preservative-free solution and is administered via subcutaneous injection. | Drug | Burosumab |
Primary outcome
Serum Phosphorus change
Time frame: 52 weeks
Change from baseline over 52 weeks in serum phosphorus with burosumab treatment.
13 secondary outcomes
Changes in 1,25(OH)2-Vitamin D
Time frame: 52 weeks
Changes in tubular reabsorption of phosphate (TRP)
Time frame: 52 weeks
Changes in TmP/GFR (the ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate
Time frame: 52 weeks
Biomechanical Marker
Time frame: 52 weeks
6-minute walk test
Time frame: 52 weeks
Sit-to-Stand test (STST)
Time frame: 2 weeks
Brief Pain Inventory (BPI)
Time frame: 52 weeks
Brief Fatigue Inventory (BFI)
Time frame: 52 weeks
SF36 item short health survey (SF-36)
Time frame: 52 weeks
PROMIS Pain Intensity
Time frame: 52 weeks
PROMIS Pain Interference
Time frame: 52 weeks
PROMIS Physical Function with Mobility Aid
Time frame: 52 weeks
PROMIS Fatigue
Time frame: 52 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 30 Jul 2026.
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.
Laura Tosi, MD principal investigator
Children's National Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Burosumab in people with Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS) and Epidermal Nevus Syndrome, run by Laura Tosi at 1 site in United States.
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 10 inclusion and 9 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 30 Jul 2026. 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 United States. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Serum Phosphorus change (time frame: 52 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 30 Jul 2026.