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

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.

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.