HypophosphatemiaPhase 3NCT03581591
Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets
A Phase 3 study testing Burosumab in people with Hypophosphatemia and Hypophosphatemic Rickets, run by Redwood Dermatology Sciences at 1 site in United States.
Trial summary
A 52 week, open label trial to assess the safety and efficacy of KRN23, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome(ENS) and associated hypophosphatemic rickets A 26 weeks extension to original study to monitor patient lab results for her safety. Read more about this study
- Who is it for?
- Ages Up to 18 years, women only
- Conditions the study is for
- Hypophosphatemia, Hypophosphatemic Rickets, Pain, Chronic
- 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
- 31 Jan 2018to 6 Dec 2019
- 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 Up to 18 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient has confirmed ENS by physician diagnosis
- Patient has confirmed FGF23 elevations in the context of low serum phosphorous < 4.1 mg/dL
- Patient able to tolerate KRN23 treatment
- Have a corrected serum calcium level < 10.8mg/dL
- Have an eGFR >60 ml/min
- Must be willing in the opinion of the investigator, to comply with study procedures and schedule
- Provide written informed consent by a parent after the study has been explained and prior to any research related procedures begin
Who cannot join
- Concomitant use of active vitamin D (i.e calcitriol) and/or exogenous phosphate supplementation. Patient will be allowed OTC Vitamin D should levels drop below <20 ng/ml
- The use or enrollment in studies using other investigational therapies including other monoclonal antibodies
- Subject and their parent not willing or not able to give written informed consent
- In the Investigators opinion, the patient may not be able to meet all the requirements for study participation
- Patient has a history of hypersensitivity to KRN23 excipients that in the opinion of the investigator, places the patient at an increased risk of adverse effects
- Patient 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.
About this study
Official title: An Open Label Trial to Assess the Safety and Efficacy of Burosumab (KRN23), an Investigational Antibody to FGF23, in a Single Pediatric Patient With Epidermal Nevus Syndrome(ENS) and Associated Hypophosphatemic Rickets
A 52 week, open label trial to assess the safety and efficacy of KRN23, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome(ENS) and associated hypophosphatemic rickets
A 26 weeks extension to original study to monitor patient lab results for her safety.
Read the detailed description
1.1 Primary Objective
The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets
1.2 Secondary Objectives
- The PD profile of KRN23 as assessed by changes from baseline over time 1,25(OH)2D, iPTH, Serum Calcium, TRP and TmP/GFR (the ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate)
- Changes in underlying skeletal disease/rickets as assessed by standard radiographs utilizing the Radiographic Global Impression of Change (RGI-C) rating scales
- Effects of KRN23 on biochemical markers of bone turnover that reflect rickets severity, alkaline phosphatase (ALP)
- Walking ability as assessed by 6-Minute Walk Test (6MWT)
- Patient/parent-Reported Outcomes as assessed by PROMIS and FPS-R rating scales
1.3 Exploratory Objective
- Dual-energy X-ray absorptiometry (DXA)
1.4 Safety Objective Assess the safety of KRN23 administration in a single patient with ENS-associated hypophosphatemic rickets, based on adverse events (AEs), laboratory assessments, cardiac imaging and renal ultrasound.
- Conditions
- Hypophosphatemia, Hypophosphatemic Rickets, Pain, Chronic
- Being tested
- Burosumab
- Medical subject headings
- Hypophosphatemia, Rickets, Hypophosphatemic, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BurosumabBiological
recombinant human IgG1 monoclonal antibody to fibroblast growth factor 23)
| Study group | Role | What they receive |
|---|---|---|
| Primary; open label | Experimental | Injection of Burosumab every two to three weeks based on Serum Phosphorus level of subject. Initial dose to be 0.3 mg/kg. Subsequent dosing will be titrated up or down depending on Serum Phosphorus level for that time period. Receives: Biological: Burosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2018
- Study start31 Jan 2018
- Primary completion6 Dec 2019
- Study completion6 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Redwood Dermatology Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Ultragenyx Pharmaceutical Inc
- Responsible party
- Sponsor
- Investigators
- Jeffrey Sugarman, MD PhD, Principal investigator, Redwood Dermatology Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03581591
- Sponsor's protocol ID
- ENSKRN23.1
- Status last verified
- Jan 2020
- First submitted
- 27 Oct 2017
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Aono Y, Yamazaki Y, Yasutake J, Kawata T, Hasegawa H, Urakawa I, Fujita T, Wada M, Yamashita T, Fukumoto S, Shimada T. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. J Bone Miner Res. 2009 Nov;24(11):1879-88. doi: 10.1359/jbmr.090509.
PubMed 19419316Aono Y, Hasegawa H, Yamazaki Y, Shimada T, Fujita T, Yamashita T, Fukumoto S. Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice. J Bone Miner Res. 2011 Apr;26(4):803-10. doi: 10.1002/jbmr.275.
PubMed 20939065Carpenter TO, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Wooddell MM, Kawakami T, Ito T, Zhang X, Humphrey J, Insogna KL, Peacock M. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. J Clin Invest. 2014 Apr;124(4):1587-97. doi: 10.1172/JCI72829. Epub 2014 Feb 24.
PubMed 24569459Lim YH, Ovejero D, Sugarman JS, Deklotz CM, Maruri A, Eichenfield LF, Kelley PK, Juppner H, Gottschalk M, Tifft CJ, Gafni RI, Boyce AM, Cowen EW, Bhattacharyya N, Guthrie LC, Gahl WA, Golas G, Loring EC, Overton JD, Mane SM, Lifton RP, Levy ML, Collins MT, Choate KA. Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia. Hum Mol Genet. 2014 Jan 15;23(2):397-407. doi: 10.1093/hmg/ddt429. Epub 2013 Sep 4.
PubMed 24006476
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. 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 (KRN23), an Investigational Antibody to FGF23, in a Single Pediatric Patient With Epidermal Nevus Syndrome(ENS) and Associated Hypophosphatemic Rickets
- ClinicalTrials.gov ID
- NCT03581591
- Acronym / sponsor ID
- ENSKRN23.1
- Conditions
- Hypophosphatemia, Hypophosphatemic Rickets, Pain, Chronic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Redwood Dermatology SciencesUniversity, hospital or other
- Collaborators
- Ultragenyx Pharmaceutical Inc
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 6 Dec 2019 (actual)
- Study completion
- 6 Dec 2019 (actual)
- First posted
- 10 Jul 2018 (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 52 week, open label trial to assess the safety and efficacy of KRN23, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome(ENS) and associated hypophosphatemic rickets
A 26 weeks extension to original study to monitor patient lab results for her safety.
Detailed description
1.1 Primary Objective
The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets
1.2 Secondary Objectives
- The PD profile of KRN23 as assessed by changes from baseline over time 1,25(OH)2D, iPTH, Serum Calcium, TRP and TmP/GFR (the ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate)
- Changes in underlying skeletal disease/rickets as assessed by standard radiographs utilizing the Radiographic Global Impression of Change (RGI-C) rating scales
- Effects of KRN23 on biochemical markers of bone turnover that reflect rickets severity, alkaline phosphatase (ALP)
- Walking ability as assessed by 6-Minute Walk Test (6MWT)
- Patient/parent-Reported Outcomes as assessed by PROMIS and FPS-R rating scales
1.3 Exploratory Objective
- Dual-energy X-ray absorptiometry (DXA)
1.4 Safety Objective Assess the safety of KRN23 administration in a single patient with ENS-associated hypophosphatemic rickets, based on adverse events (AEs), laboratory assessments, cardiac imaging and renal ultrasound.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Primary; open label | Experimental | Biological: BurosumabInjection of Burosumab every two to three weeks based on Serum Phosphorus level of subject. Initial dose to be 0.3 mg/kg. Subsequent dosing will be titrated up or down depending on Serum Phosphorus level for that time period. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Patient has confirmed ENS by physician diagnosis
- Patient has confirmed FGF23 elevations in the context of low serum phosphorous < 4.1 mg/dL
- Patient able to tolerate KRN23 treatment
- Have a corrected serum calcium level < 10.8mg/dL
- Have an eGFR >60 ml/min
Key exclusion criteria (6 listed)
- Concomitant use of active vitamin D (i.e calcitriol) and/or exogenous phosphate supplementation. Patient will be allowed OTC Vitamin D should levels drop below <20 ng/ml
- The use or enrollment in studies using other investigational therapies including other monoclonal antibodies
- Subject and their parent not willing or not able to give written informed consent
- In the Investigators opinion, the patient may not be able to meet all the requirements for study participation
- Patient has a history of hypersensitivity to KRN23 excipients that in the opinion of the investigator, places the patient at an increased risk of adverse effects
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 |
|---|---|---|
| Burosumabrecombinant human IgG1 monoclonal antibody to fibroblast growth factor 23) | Biological | Primary; open label |
Primary outcome
The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets
Time frame: 18 months
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 18 Jan 2020.
- Background: PubMed 19419316Aono Y, Yamazaki Y, Yasutake J, Kawata T, Hasegawa H, Urakawa I, Fujita T, Wada M, Yamashita T, Fukumoto S, Shimada T. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. J Bone Miner Res. 2009 Nov;24(11):1879-88. doi: 10.1359/jbmr.090509.
- Background: PubMed 20939065Aono Y, Hasegawa H, Yamazaki Y, Shimada T, Fujita T, Yamashita T, Fukumoto S. Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice. J Bone Miner Res. 2011 Apr;26(4):803-10. doi: 10.1002/jbmr.275.
- Background: PubMed 24569459Carpenter TO, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Wooddell MM, Kawakami T, Ito T, Zhang X, Humphrey J, Insogna KL, Peacock M. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. J Clin Invest. 2014 Apr;124(4):1587-97. doi: 10.1172/JCI72829. Epub 2014 Feb 24.
- Background: PubMed 24006476Lim YH, Ovejero D, Sugarman JS, Deklotz CM, Maruri A, Eichenfield LF, Kelley PK, Juppner H, Gottschalk M, Tifft CJ, Gafni RI, Boyce AM, Cowen EW, Bhattacharyya N, Guthrie LC, Gahl WA, Golas G, Loring EC, Overton JD, Mane SM, Lifton RP, Levy ML, Collins MT, Choate KA. Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia. Hum Mol Genet. 2014 Jan 15;23(2):397-407. doi: 10.1093/hmg/ddt429. Epub 2013 Sep 4.
Related trials for Hypophosphatemia
RecruitingPhase 1/2
A First-in-human Study of KK8123 in Adults With X-linked Hypophosphatemia
X-linked Hypophosphatemia
Not yet recruitingEarly Phase 1
Phosphate & Kidney Stones
Kidney Stones, Calcium Oxalate Kidney Stones
Recruiting
Study of the Impact of Phosphate Supplementation on FGF23 Concentrations in Patients With Hypophosphatemia
Calcium-phosphorus Metabolism
Not yet recruitingObservational study
Respiratory Quotient and Phosphate Changes During Early Critical Illness
Refeeding Syndrome, Critical Illness
Active, not recruitingObservational study
X-linked Hypophosphatemia Disease Monitoring Program
X-linked Hypophosphatemia, Hypophosphatemic Rickets
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.
Jeffrey Sugarman, MD PhD principal investigator
Redwood Dermatology Sciences
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 Hypophosphatemia and Hypophosphatemic Rickets, run by Redwood Dermatology Sciences 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 7 inclusion and 6 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 18 Jan 2020. 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?
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?
The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets (time frame: 18 months). 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 NCT03581591, which also lists 4 linked publications.
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 18 Jan 2020.