Study to Assess the Safety, Pharmacokinetics and Efficacy of KRN23 in Adult Chinese Patients With XLH
Study to Assess the Safety, Pharmacokinetics and Efficacy of KRN23 in Adult Chinese Patients With XLH
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in
 adult Chinese patients with XLH
Inclusion Criteria:

 1. Male or female Chinese patients, aged 18 to 65 years (inclusive) at the time of
 signing the ICF

 2. Diagnosis of XLH supported by classic clinical features of adult XLH (such as short
 stature or bowed legs) and at least either of the following at screening:

 -  Confirmed PHEX mutation (prior to the study with historic record) in the patient
 or a directly related family member with appropriate X linked inheritance

 -  Serum iFGF23 level ≥30 pg/mL by the Kainos assay at Screening

 3. Biochemical findings consistent with XLH following overnight fasting (≥8 hours) at
 Screening:

 -  Serum phosphorus <2.5 mg/dL (0.81 mmol/L). Serum phosphorus level may be re
 tested (once only) at least 7 days after discontinuation of therapy, if
 applicable.

 -  TmP/GFR of <2.5 mg/dL

 4. Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥4
 on the BPI Worst Pain question at Screening (Skeletal pain that, in the opinion of the
 investigator or subinvestigator, is attributed solely to causes other than
 XLH/osteomalacia [e.g., 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)

 5. Patients who are taking chronic pain medications (including narcotic pain
 medications/opioids) must be on a stable regimen for at least 21 days before signing
 the ICF and be willing to maintain the medications at the same stable dose(s) and
 schedule throughout the study. The dose must not exceed 60 mg oral morphine
 equivalents/day

 6. Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D [or
 metabolites/analogs])

 7. Written informed consent provided after the nature of the study has been explained and
 prior to any research related procedures

 8. Willing to provide access to prior medical records for the collection of biochemical
 and radiographic data and disease history

 9. Have a negative pregnancy test at Screening and be willing to have additional
 pregnancy tests during the study (female patients of child-bearing potential only)

 10. Be willing to use an effective method of contraception while participating in the
 study (sexually active patients of child bearing potential) and for 12 weeks after
 last dose of study drug. Women of non child bearing potential are defined as
 permanently sterile (i.e. due to hysterectomy or bilateral oophorectomy) or
 postmenopausal (defined as at least 12 months postcessation of menses without an
 alternative medical cause). Postmenopausal status of female patients will be confirmed
 with a Screening serum follicle stimulating hormone (FSH) level >40 mIU/mL

 11. Be willing and able to complete all aspects of the study, adhere to the study visit
 schedule, and comply with the assessments, as judged by the investigator or
 subinvestigator

 12. Have completed entries for ≥4 of 7 consecutive days of the patient diaries before Week
 -14

 Exclusion Criteria:

 1. Use of a pharmacologic vitamin D, its metabolites, or analogs, and oral phosphate for
 treatment of XLH within 14 days prior to Screening.

 2. Use of aluminum hydroxide antacids, acetazolamide, thiazide diuretics and/or systemic
 corticosteroids within 14 days prior to Week -14

 3. Corrected serum calcium level ≥10.8 mg/dL (2.69 mmol/L) at Screening

 4. Plasma iPTH ≥2.5 times the upper limit of normal at Screening

 5. Uncontrolled diabetes mellitus, defined as HbA1c >7.5% at Screening

 6. Use of medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics) within
 60 days before signing the ICF

 7. Use of oral bisphosphonates in the 2 years before signing the ICF

 8. Planned or recommended orthopedic surgery within the clinical trial period

 9. History of traumatic fracture or orthopedic surgery within 6 months before signing the
 ICF

 10. Use of KRN23, or any other therapeutic mAb within 90 days before signing the ICF

 11. Use of any investigational product or investigational medical device within 30 days
 before signing the ICF, or requirement for any investigational agent prior to
 completion of all scheduled study assessments

 12. Pregnant or breastfeeding at Screening or Week -14, or intention to become pregnant
 (the patient or partner) at any time during the study

 13. Unable or unwilling to withhold prohibited medications throughout the study

 14. Presence or history of any hypersensitivity, or allergic or anaphylactic reactions to
 any mAb or KRN23 excipients that, in the judgment of the investigator or
 subinvestigator, places the patient at increased risk for adverse effects

 15. Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen
 (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening, or prior history of
 positive test

 16. History of recurrent infection or predisposition to infection, or of known
 immunodeficiency

 17. Presence of malignant neoplasm (except basal cell carcinoma)

 18. Presence of a concurrent disease or condition that would interfere with study
 participation or affect safety

 19. Presence or history of any condition that, in the view of the investigator or
 subinvestigator, places the patient at high risk of poor treatment compliance or of
 not completing the study