A Trial to Assess the Safety and Efficacy of KRN23 in Epidermal Nevus Syndrome (ENS)
Condition: Epidermal Nevus Syndrome
MeSH terms: Nevus; Nevus, Sebaceous of Jadassohn; Syndrome
Intervention: Crysvita (burosumab-twza) Treatment
Intervention description: KRN23 is a fully human IgG1monoclonal antibody that binds to and inhibits the activity of FGF23, leading to an increase in serum phosphorus levels. It is a potential therapeutic candidate for the treatment of XLH, Tumor-Induced Osteomalacia (TIO), and the rickets/osteomalacia resulting from Epidermal Nevus Syndrome (ENS). All of these conditions are diseases of bone hypomineralization, caused by urinary phosphate wasting due to elevated levels of FGF23.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Male
Minimum age: 6 Months
Healthy volunteers: No
Keywords: epidermal nevus syndrome; burosumab-twza

Summary:

      KRN23 is a fully human immunoglobulin monoclonal antibody (mAb) that binds to and inhibits
      the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum
      phosphorus levels. There are multiple disorders that result in unusually high circulating
      levels of FGF23, which in turn result in renal phosphate wasting and reduced 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. KRN23 has been studied in one of these disorders, X-linked
      hypophosphatemia (XLH). In single- and repeat-dose clinical studies in subjects with XLH,
      subcutaneous (SC) administration of KRN23 consistently increased and sustained serum
      phosphorus levels and tubular reabsorption of phosphate (TRP) without a major impact on urine
      calcium levels or vitamin D metabolism. Positive results were also observed in a nonclinical
      pharmacology model of XLH. It is hypothesized that KRN23 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. The
      primary objective is to study the effect of KRN23 treatment on normalizing age-adjusted
      fasting serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome
      associated hypophosphatemic rickets.
    

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

        Exclusion Criteria:

          -  Patient should not use CRYSVITA with Oral phosphate or active Vitamin D analogs.

          -  Patient and investigator should not initiate CRYSVITA if Phosphorus level is within or
             above normal.

          -  CRYSVITA is contraindicated in patients with severe renal impairment or end stage
             renal disease because these conditions are associated with abnormal mineral
             metabolism.

          -  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 subject may not be able to meet all the requirements
             for study participation

          -  Subject has a history of hypersensitivity to KRN23 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.