Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)
Condition: X-Linked Hypophosphatemia
MeSH terms: Familial Hypophosphatemic Rickets; Hypophosphatemia
Intervention: KRN23
Intervention description: solution for SC injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Healthy volunteers: No
Keywords: XLH; FGF23; KRN23

Summary:

      The primary objectives of this study are to:

        -  Assess the long-term safety of KRN23 subcutaneous (SC) administration in adult subjects
           with XLH

        -  Assess the proportion of subjects achieving serum phosphorus levels in the normal range
           (2.5-4.5 mg/dL) with long-term administration of KRN23

        -  Assess long-term pharmacodynamics (PD) of KRN23 as measured by changes in the following:
           serum intact parathyroid hormone (iPTH); serum and urinary phosphorus; ratio of renal
           tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) and
           tubular reabsorption of phosphate (TRP); serum 1,25-dihydroxy vitamin D (1,25[OH]2D);
           serum fibroblast growth factor 23 (FGF23); bone biomarkers: serum alkaline phosphatase
           (ALP), bone-specific ALP (BALP), carboxy terminal crosslinked telopeptide of type I
           collagen (CTx), and procollagen type 1 N-terminal propeptide (P1NP)

        -  Assess long-term immunogenicity of KRN23 as measured by presence of anti-KRN23 antibody
           (ADA)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have participated in Kyowa Hakko Kirin Pharma, Inc.'s KRN23-INT-001 (NCT01340482) or
             KRN23-INT-002 (NCT01571596) studies (received at least 2 doses of KRN23)

          2. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min or eGFR of 45 to < 60 mL/min
             at Screening with confirmation that the renal insufficiency was not due to
             nephrocalcinosis.

          3. Sexually active subjects must be willing to use an acceptable method of contraception
             (e.g., double barrier method) while participating in the study and for 30 days after
             receiving the last dose of KRN23.

        Exclusion Criteria:

          1. Subject experienced a safety-related event in the KRN23-INT-001 or KRN23-INT-002 study
             that, in the opinion of the investigator and sponsor, precludes resuming KRN23
             treatment.

          2. Presence of nephrocalcinosis on renal ultrasound that, in the opinion of the
             investigator and sponsor, precludes resuming KRN23 treatment.

          3. Pregnant or breastfeeding at Screening or planning to become pregnant (self or
             partner) at any time during the study.

          4. Participation in an investigational drug or device trial within 30 days of enrollment
             (other than KRN23-INT-001 or KRN23-INT-002).

          5. Use of a pharmacologic vitamin D metabolite or analog (e.g., calcitriol,
             doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g.,
             Maalox® and Mylanta®) within 21 days prior to Screening or during the study.

          6. Use of medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet,
             calcimimetics) within 2 months prior to Screening.