Open Label Study of KRN23 on Osteomalacia in Adults With X-linked Hypophosphatemia (XLH)

Inclusion Criteria

• Male or female, aged 18 - 65 years, inclusive
• Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs), and at least one of the following at Screening:
• Documented phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX) PHEX mutation in either the patient or in a directly related family member with appropriate X-linked inheritance
• Serum intact FGF23 (iFGF23) level > 30 pg/mL by Kainos assay
• Biochemical findings consistent with XLH based on overnight fasting (min. 8 hours):
• Serum phosphorus < 2.5 mg/dL at Screening
• Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) < 2.5 mg/dL at Screening
• Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥ 4 on the Brief Pain Inventory question 3 (BPI-Q3, Worst Pain) at Screening. (Skeletal pain that, in the opinion of the investigator, is attributed solely to causes other than XLH/osteomalacia-for example, back pain or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location-in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) or estimated glomerular filtration rate (eGFR) eGFR of 45 to <60 mL/min at Screening with confirmation that the renal insufficiency is not due to nephrocalcinosis
• Provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures. If the subject in a minor, provide written assent and have a legally authorized representative willing and able to provide written informed consent, after the nature of the study has been explained, and prior to any research-related procedures
• Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
• Females of child-bearing potential must have a negative urine pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not to be of childbearing potential include those who have been in menopause for at least two years prior to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total hysterectomy or bilateral salpingo-oophorectomy.
• Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a total hysterectomy or a bilateral salpingo-oophorectomy and are sexually active must consent to use two effective methods of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence) from the period following the signing of the informed consent through 12 weeks after last dose of study drug
• Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments

Exclusion Criteria

• Use of any pharmacologic vitamin D metabolite or analog (e.g. calcitriol, doxercalciferol, and paricalcitol) within the 2 years before Screening
• Use of oral phosphate within 2 years before Screening
• Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening
• Use of bisphosphonates in the 2 years prior to Screening
• Use of denosumab in the 6 months prior to Screening
• Use of teriparatide in the 2 months prior to Screening
• Chronic use of systemic corticosteroids defined as more than 10 days in the 2 months prior to Screening
• Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening
• Serum intact