A Study of KRN23 in Subjects With Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome

Inclusion criteria

• Aged ≥ 18 years
• Diagnosis of Tumor-Induced Osteomalacia(TIO) or Epidermal Nevus Syndrome(ENS) and not amenable to receive surgical excision of the offending tumor/lesion
• Serum phosphorus level < 2.5 mg/dL
• Serum FGF23 level ≥ 100 pg/mL
• Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate< 2.5 mg/dL
• Estimated glomerular filtration rate (eGFR) at screening ≥ 60 mL/min/1.73 m2, or eGFR ≥ 30 and < 60 mL/min/1.73 m2 with an evidence of no renal failure related to nephrocalcinosis
• Corrected serum calcium level < 10.8 mg/dL
• For female subjects of childbearing potential; negative urine pregnancy test and willingness to undergo additional pregnancy tests during the study
• Willingness to use an acceptable method of contraception while participating in the study
• Willingness to provide access to prior medical records to determine eligibility including data on imaging tests, blood chemistry, diagnosis, medication, and surgical history
• Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by the investigator or subinvestigator

Exclusion criteria

• Use of the following drugs within 14 days prior to screening: pharmacologic vitamin D metabolites or analogs, or drugs for treating TIO/ENS including oral phosphate, aluminum hydroxide antacids, acetazolamide, or thiazide diuretics
• Medication to suppress parathyroid hormone (PTH) within 60 days prior to screening
• Blood or blood product transfusion within 60 days prior to screening
• Chemotherapy for TIO or other malignant tumors within 4 months prior to screening
• History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody
• Predisposition to infection, or history of recurrent infection or known immunodeficiency
• Pregnant or breastfeeding at screening or intention to become pregnant during the study; for male subjects, the partner's intention to become pregnant during the study
• Use of an investigational product or device within 4 months prior to screening, or planning to receive other investigational product before completing all assessments in this study
• Use of therapeutic monoclonal antibodies including KRN23 within 90 days prior to screening
• History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies
• Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator

At the time of switching to the post-marketing study:

• Voluntary written informed consent to participate in the post-marketing study (if aged < 20 years at the time of consent, written informed consent must be obtained from his or her legally acceptable representative as well)
• Switching to the post-marketing study is necessary and appropriate for the subject from the viewpoint of efficacy and safety, as judged by the investigator or subinvestigator.