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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: An Open-Label, Single-Arm, Phase 3 Study to Evaluate the Effects of KRN23 on Osteomalacia in Adults With X-linked Hypophosphatemia (XLH)

Brief Summary: UX023-CL304 is a Phase 3 open-label, single-arm, multicenter study to establish the effects of KRN23 on bone quality and osteomalacia associated with XLH. Approximately 14 adult subjects with a diagnosis of XLH supported by typical clinical and biochemical features and who have not received oral phosphate and vitamin D therapy in the past two years will be enrolled. Iliac crest bone biopsies will be performed at baseline and end of study. Baseline histologic and histomorphometric assessments of the bone biopsy specimens will be performed as each biopsy is completed to assess sample quality and confirm the presence of osteomalacia in at least 8 subjects.

Detailed Summary:
Sponsor: Ultragenyx Pharmaceutical Inc

Current Primary Outcome:

  • Osteoid Thickness (O.Th) [ Time Frame: 48 weeks ]
  • Osteoid surface/Bone surface (OS/BS) [ Time Frame: 48 weeks ]
  • Mineralization lag time (MLt) [ Time Frame: 48 weeks ]
  • Osteoid volume/Bone volume (OV/BV) [ Time Frame: 48 weeks ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal (LLN) at the mid-point of the dose interval (i.e., Weeks 2, 6, 14, and 22), as averaged across dose cycles between baseline and Week 24. [ Time Frame: 24 weeks ]
  • Changes in mineral apposition rate (MAR) [ Time Frame: 48 weeks ]
  • Changes in mineralizing surface (MS/BS) [ Time Frame: 48 weeks ]
  • Changes in bone formation rate (BFR) [ Time Frame: 48 weeks ]
  • Proportion of subjects achieving mean serum phosphorus levels above the Lower Limit of Normal (LLN) at the end of the dosing cycle [ Time Frame: 24 weeks ]
  • Mean change of serum phosphorus levels at the mid-point of dosing cycle and end of dosing cycle [ Time Frame: 24 weeks ]
  • Percentage change of serum phosphorus levels at the mid-point of dosing cycle and end of dosing cycle [ Time Frame: 24 weeks ]
  • Cumulative exposure of serum phosphorus levels: area under the curve (AUC) [ Time Frame: 24 weeks ]
  • Change from baseline over time in serum 1,25(OH)2D [ Time Frame: 24 weeks ]
  • Change from baseline over time in urinary phosphorus [ Time Frame: 24 weeks ]
  • Change from baseline over time in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) [ Time Frame: 24 weeks ]
  • Change from baseline over time in tubular reabsorption of phosphate (TRP) [ Time Frame: 24 weeks ]
  • Change from baseline over time in procollagen type 1 N-propeptide (P1NP) [ Time Frame: 24 weeks ]
  • Change from baseline over time in carboxy-terminal cross-linked telopeptide of type I collagen (CTx) [ Time Frame: 24 weeks ]
  • Change from baseline over time in bone-specific alkaline phosphatase (BALP) [ Time Frame: 24 weeks ]
  • Percent change from baseline over time in procollagen type 1 N-propeptide (P1NP), carboxy-terminal cross-linked telopeptide of type I collagen (CTx), and bone-specific alkaline phosphatase (BALP) [ Time Frame: 24 weeks ]


Original Secondary Outcome: Same as current

Information By: Ultragenyx Pharmaceutical Inc

Dates:
Date Received: August 25, 2015
Date Started: December 2015
Date Completion: August 2017
Last Updated: May 2, 2017
Last Verified: May 2017