The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in adult Chinese patients with XLH
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
KRN23 is a sterile clear colourless and preservative free solution supplied in single use 5 mL vials containing 1 mL of KRN23 at a concentration of 30mg/mL
Peking Union Medical College Hospital
Beijing, China
The First Medical Center of Chinese People's Liberation Army General Hospital
Beijing, China
Nanfang Hospital
Guangzhou, China
The Second Affiliated Hospital of Zhejiang University
Hangzhou, China
Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, and 48
Change in Brief Pain Inventory (BPI) Worst Pain score over time
Change from baseline to post-baseline visits in BPI-Q3 (Worst Pain) score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
Time frame: Weeks 0, 12, 24, 36, and 48
Change in BPI Pain Severity score and Pain Interference score over time
Change from baseline to post-baseline visits in BPI pain severity score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
Time frame: Weeks 0, 12, 24, 36, and 48
Change in BPI Pain Interference score over time
Change from baseline to post-baseline visits in BPI pain interference score as recorded on the day of the study visit. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes).
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Shanghai 6th Hospital
Shanghai, China
Time frame: Weeks 0, 12, 24, 36, and 48
Change in the Stiffness and Physical Function domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over time
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.
Time frame: Weeks 0, 12, 24, 36, and 48
Change in the health related QOL assessment by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function over time
The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013), (NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Physical Function Domain, increases indicate greater mobility.
Time frame: Weeks 0, 12, 24, 36, and 48
The proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L]) at the end of the dosing cycle
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, and 48
The proportion of subjects achieving mean serum phosphorus levels above the LLN (2.5 mg/dL [0.81 mmol/L]) at the mid-point of dosing cycle
Time frame: Weeks 2, 6, 10, 14, 18 and 22
CFB in mean serum phosphorus level at the mid-time point of dosing cycle
Time frame: Weeks 2, 6, 10, 14, 18 and 22
Mean percent CFB in serum phosphorus levels averaged at the end of dose cycles
Time frame: Baseline to Week 48
Cumulative exposure: area under curve (AUC) of serum phosphorus
Time frame: Baseline to Week 48
Change in serum 1,25(OH)2D over time
Time frame: Baseline to Week 48
Change in urinary phosphorus over time
Time frame: Baseline to Week 48
Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time
Time frame: Baseline to Week 48