The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in adult Chinese patients with TIO
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
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
West China Hospital, Sichuan University
Chengdu, China
Shanghai Jiaotong University Affiliated Sixth People's Hospital
Shanghai, China
Change from Baseline in mean serum phosphorus level at the end of the dosing cycle.
Time frame: Week 20, 24, 28, 32, 36, 40, 44 and 48
Change from Baseline in mean serum phosphorus level.
Time frame: Week 22
Proportion of patients achieving serum phosphorus level above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L])
Time frame: Week 22
Proportion of patients achieving mean serum phosphorus level above the LLN (2.5 mg/dL [0.81 mmol/L]) at the end of the dose cycle as averaged across dose period
Time frame: Weeks 20, 24, 28, 32, 36, 40, 44 and 48
Change from Baseline in mean level of serum 1,25(OH)2D over time
Time frame: Week 0, 1, 2, 12, 16, 24, 36 and 48
Change from Baseline in mean level of serum creatinine over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in mean level of urinary phosphorus over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in level of tubular reabsorption of phosphate(TRP) over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change in concentration of alkaline phosphatase (ALP) over time
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Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of bone-specific alkaline phosphatase (BALP) over time
Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of carboxy-terminal cross-linked telopeptide of type 1 collagen (CTx) over time
Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of procollagen type 1 N propeptide(P1NP) over time
Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of osteocalcin (OC) over time
Time frame: Week 0, 8, 16, 24 and 48
Change from Baseline in six-minute walking test (6MWT) over time
This test will measure the distance that the subject can walk a previously measured course in a period of 6 minutes.
Time frame: Week 0, 12, 24 and 48
Change from Baseline in Brief Pain Inventory (BPI) score over time
Evaluate the degree of pain and its impact on daily functioning over previous 24 hours, the subject will fill out a 15-item self-administered questionnaire. 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: Week 0, 12, 24 and 48
Change from Baseline in Brief Fatigue Inventory (BFI) score over time
Evaluate the degree of fatigue and its impact on daily functioning over previous 24 hours, the subject will fill out a 9-item self-administered questionnaire. Two dimensions are measured: fatigue severity (now, usual and worst) and the impact of fatigue on functioning (fatigue interference with general activity, mood, walking ability, normal work, relations with other people, enjoyment of life). The severity of fatigue in the last 24 hours is rated on a scale of 0 (no fatigue or does not interfere) to 10 (fatigue as bad as you can imagine or completely interferes). Scores are normalized to a 0-10 metric where 0 was the best health state and 90 was the worst.
Time frame: Week 0, 12, 24 and 48
36-item short-form health survey (SF-36) scores to examine health-related Quality of Life
Evaluate physical and mental health status, the subject will fill out a 36-item self-administered questionnaire. The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). The score will be calculated based on scoring system, and the Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
Time frame: Week 0, 12, 24 and 48