Clinical Trial: Study of KRN23 in Adult Subjects With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: A Phase 2 Open-Label Trial to Assess the Efficacy and Safety of KRN23, an Antibody to FGF23, in Subjects With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome
Brief Summary: UX023T-CL201 is an, open-label, Phase 2 study. The study will be conducted in adults aged 18 years or older with TIO or ENS whose tumor/skin lesion is inoperable to assess the efficacy and safety of KRN23 administered via subcutaneous injections monthly (every 4 weeks) for a total of 144 weeks. Subjects will need to discontinue oral phosphate and vitamin D metabolite therapy prior to randomization and throughout the duration of the study.
Detailed Summary:
Sponsor: Ultragenyx Pharmaceutical Inc
Current Primary Outcome:
- The proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal. [ Time Frame: 48 Weeks ]
- Percent change from baseline in excess osteoid based on analysis of iliac crest bone biopsies after 48 weeks of KRN23 treatment [ Time Frame: 48 Weeks ]
Original Primary Outcome: Incidence, frequency, and severity of adverse events and serious adverse events [ Time Frame: 48 weeks of treatment ]
Current Secondary Outcome:
- Incidence, frequency, and severity of adverse events and serious adverse [ Time Frame: 144 Weeks ]
- PK profile of serum levels of KRN23 to assess KRN23 concentration and possible accumulation [ Time Frame: Baseline (Weeks 0, 2, 4) and 6 months (Weeks 20, 22, 24) ]
- Change from Baseline in serum FGF23 [ Time Frame: 144 weeks ]
- Change from Baseline in serum ALP [ Time Frame: 144 weeks ]
- Change from Baseline in serum 1,25(OH)2D [ Time Frame: 144 weeks ]
- Change from Baseline in serum phosphorus [ Time Frame: 144 weeks ]
- Change from Baseline in TRP and TMP/GFR [ Time Frame: 144 weeks ]
- Change from Baseline in biomarkers of bone turnover biomarkers including BALP, CTx, P1NP, and osteocalcin [ Time Frame: 144 weeks ]
- Brief Fatigue Inventory (BFI) [ Time Frame: 144 Weeks ]
- Brief Pain Inventory (BPI) [ Time Frame: 144 Weeks ]
- Short Form Health Survey (SF36) [ Time Frame: 144 Weeks ]
- Western Ontario and McMaster Universities osteoarthritis index (WOMAC) [ Time Frame: 48 Weeks ]
- Sit to Stand (STS) [ Time Frame: 48 Weeks ]
- Hand Held Dynamometry (HHD) [ Time Frame: 48 Weeks ]
- Timed Up and Go (TUG) [ Time Frame: 48 Weeks ]
- Weighted Arm Lift (WAL) test [ Time Frame: 48 weeks ]
- 6-Minute Walk Test [ Time Frame: 48 Weeks ]
Original Secondary Outcome:
- PK profile of serum levels of KRN23 to assess KRN23 concentration and possible accumulation [ Time Frame: Baseline (Weeks 0, 2, 4) and 6 months (Weeks 20, 22, 24) ]
- Change from Baseline in serum FGF23 [ Time Frame: 48 weeks ]
- Change from Baseline in serum ALP [ Time Frame: 48 weeks ]
- Change from Baseline in serum 1,25(OH)2D [ Time Frame: 48 weeks ]
- Change from Baseline in serum and urinary phosphorus [ Time Frame: 48 weeks ]
- Change from Baseline in TRP and TMP/GFR [ Time Frame: 48 weeks ]
- Change from Baseline in biomarkers of bone remodeling including BALP, CTx, P1NP, and osteocalcin [ Time Frame: 48 weeks ]
- Evaluate changes in skeletal disease/osteomalacia through trans-iliac crest bone biopsy [ Time Frame: 48 weeks ]
- Evaluate changes in skeletal disease/osteomalacia through standard radiographs [ Time Frame: 48 weeks ]
- Evaluate changes in skeletal disease/osteomalacia through DXA [ Time Frame: 48 weeks ]
- Evaluate changes in skeletal disease/osteomalacia through 99Tc-labelled bone scan [ Time Frame: 48 weeks ]
- Evaluate changes in skeletal disease/osteomalacia through XTremeCT [ Time Frame: 48 Weeks ]
- 6 Minute Walk Test (6MWT) [ Time Frame: 48 Weeks ]
- Hand Held Dynamometry (HHD) [ Time Frame: 48 Weeks ]
- Timed Up and Go (TUG) [ Time Frame: 48 Weeks ]
- Brief Pain Inventory (BPI) [ Time Frame: 48 Weeks ]
- Short Form Health Survey (SF36) [ Time Frame: 48 Weeks ]
- Western Ontario and McMaster Universities osteoarthritis index (WOMAC) [ Time Frame: 48 Weeks ]
Information By: Ultragenyx Pharmaceutical Inc
Dates:
Date Received: November 24, 2014
Date Started: April 23, 2015
Date Completion: May 2019
Last Updated: May 2, 2017
Last Verified: May 2017