- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03581591
Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets
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.
Study Overview
Status
Intervention / Treatment
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
1. 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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Utah
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Clinton, Utah, United States, 84015
- The Focus Center, PC
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
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: Primary; open label
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.
|
recombinant human IgG1 monoclonal antibody to fibroblast growth factor 23)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
18 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jeffrey Sugarman, MD PhD, Redwood Dermatology Sciences
Publications and helpful links
General 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.
- Aono 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.
- Carpenter 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.
- Lim 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Kidney Diseases
- Urologic Diseases
- Pain
- Neurologic Manifestations
- Nutrition Disorders
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Avitaminosis
- Deficiency Diseases
- Malnutrition
- Bone Diseases
- Metabolism, Inborn Errors
- Bone Diseases, Metabolic
- Renal Tubular Transport, Inborn Errors
- Calcium Metabolism Disorders
- Metal Metabolism, Inborn Errors
- Phosphorus Metabolism Disorders
- Vitamin D Deficiency
- Hypophosphatemia, Familial
- Chronic Pain
- Rickets
- Familial Hypophosphatemic Rickets
- Hypophosphatemia
- Rickets, Hypophosphatemic
Other Study ID Numbers
- ENSKRN23.1
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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