Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets

Study Overview
=================
Brief 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.

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.

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

Conditions
-----------------
Hypophosphatemia, Hypophosphatemic Rickets, Pain, Chronic

Intervention / Treatment
-----------------
* Biological: Burosumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary; open label<br>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. | Biological: Burosumab<br>* recombinant human IgG1 monoclonal antibody to fibroblast growth factor 23)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |  | 18 months |