Study of Burosumab (KRN23) in Adults With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)
Condition: Tumor Induced Osteomalacia (TIO); Epidermal Nevus Syndrome (ENS)
MeSH terms: Nevus; Neoplasms, Connective Tissue; Nevus, Sebaceous of Jadassohn; Osteomalacia; Syndrome
Intervention: Burosumab
Intervention description: Solution for subcutaneous injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: TIO; ENS; FGF23; KRN23

Summary:

      The primary objectives of this study are to evaluate the effect of burosumab treatment on:

        -  Increasing serum phosphorus levels in adults with TIO or ENS-associated osteomalacia

        -  Improvement in TIO/ENS-associated osteomalacia as determined by osteoid thickness
           (O.Th), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV) and
           mineralization lag time (MLt).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have a clinical diagnosis of TIO/ENS-associated osteomalacia based on evidence of
             excessive fibroblast growth factor 23 (FGF23) that was not amenable to cure by
             surgical excision of the underlying tumor/lesion (documented by Investigator).

          2. Be ≥ 18 years of age

          3. Have a fasting serum phosphorus level < 2.5 mg/dL

          4. Have an FGF23 level ≥ 100 pg/mL by Kainos assay

          5. Have a ratio of renal tubular maximum reabsorption rate of phosphate to glomerular
             filtration rate (TmP/GFR) < 2.5 mg/dL

          6. Have an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using Cockcroft-Gault
             formula). Subjects with eGFR ≥ 30 but < 60 mL/min will be considered eligible as long
             as in the opinion of the investigator the decline in renal function is not related to
             nephrocalcinosis.

          7. Have a corrected serum calcium level < 10.8 mg/dL

          8. Females of child-bearing potential must have a negative urine pregnancy test at
             Screening and Baseline and be willing to have additional pregnancy tests during the
             study. Females considered not to be of childbearing potential include those who have
             not experienced menarche, are post-menopausal (defined as having no menses for at
             least 12 months without an alternative medical cause) or are permanently sterile due
             to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.

          9. Be willing to use 2 forms of effective methods of contraception while participating in
             the study (sexually active subjects) and for 12 weeks after last dose of study drug.

         10. Be willing to provide access to prior medical records to determine eligibility
             including imaging, biochemical, and diagnostic, medical, and surgical history data

         11. Provide written informed consent after the nature of the study has been explained, and
             prior to any research-related procedures

         12. Be willing and able to complete all aspects of the study, adhere to the study visit
             schedule and comply with the assessments (in the opinion of the investigator)

        Exclusion Criteria:

          1. Have a prior diagnosis of human immunodeficiency virus (HIV), hepatitis B and/or
             hepatitis C

          2. Have a history of recurrent infection, a predisposition to infection, or a known
             immunodeficiency

          3. Are pregnant or breastfeeding at Screening or are planning to become pregnant (self or
             partner) at any time during the study

          4. Have participated in an investigational drug or device trial within 30 days prior to
             Screening or are currently enrolled in another study of an investigational product or
             device

          5. Have used a therapeutic monoclonal antibody (mAb), including KRN23, within 90 days
             prior to Screening or have a history of allergic or anaphylactic reactions to any mAb

          6. Have or a have a history of any hypersensitivity to KRN23 excipients that, in the
             judgment of the investigator, places the subject at increased risk for adverse effects

          7. Have used a pharmacologic vitamin D metabolite or its analog (e.g., calcitriol,
             doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g.,
             Maalox® and Mylanta®) within 2 weeks prior to Screening or during the study

          8. Have used medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®,
             cinacalcet, calcimimetics) within 2 months prior to Screening

          9. Have a history of malignancy within 5 years of study entry with the exception of
             phosphaturic mesenchymal tumors (PMTs) of the mixed connective tissue type or
             non-melanoma skin cancers such as basal cell skin cancer

         10. Have donated blood or blood products within 60 days prior to Screening

         11. Have a history of allergic reaction to or have shown adverse reactions to a
             tetracycline (e.g., tetracycline hydrochloride [HCl] and demeclocycline),
             benzodiazepines, fentanyl or lidocaine

         12. Have any condition, which in the opinion of the investigator and sponsor, could
             present a concern for either subject safety or difficulty with data interpretation