The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in pediatric Chinese patients with XLH
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
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
Guangzhou Women and Children Medical Center
Guangzhou, China
Shanghai 6th Hospital
Shanghai, China
Shanghai Xinhua Hopsital
Shanghai, China
Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle
Time frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64
Change in rickets at Weeks 40 and 64 as examined by the Radiograph Global Impression of Change (RGI-C) global score
Changes in the severity of rickets and bowing were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).
Time frame: Weeks 40 and 64
Change in Rickets Severity Score (RSS) total score at Weeks 40 and 64
The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, lucency, separation, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees (the total score is the sum of the wrist and knee score). Higher scores indicate greater rickets severity.
Time frame: Weeks 40 and 64
Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score at Weeks 40 and 64
Changes in the severity of lower extremity skeletal abnormalities, including genu varum and genu valgus, were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing), +2 = much better (substantial healing), +1 = minimally better (i.e., minimal healing), 0 = unchanged, -1 = minimally worse (minimal worsening), -2 = much worse (moderate worsening), -3 = very much worse (severe worsening).
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Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
Wuhan, China
Time frame: Weeks 40 and 64
Change in serum phosphorus over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in alkaline phosphatase (ALP) over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in urinary phosphorus over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in recumbent length/standing height in cm, height for age z scores
Time frame: Weeks 0, 24, 40 and 64
Change in growth velocity from pre-treatment and post-treatment over time
Time frame: Weeks 0, 24, 40 and 64
Change in growth velocity z scores from pre-treatment and post-treatment over time
Time frame: Weeks 0, 24, 40 and 64
Six-minute walking test (6MWT) results to examine walking ability (total distance; patients ≥5 years at the time of signing the ICF only)
Time frame: Weeks 0, 24, 40 and 64
Six-minute walking test (6MWT) results to examine walking ability (percent of predicted normal; patients ≥5 years at the time of signing the ICF only)
Time frame: Weeks 0, 24, 40 and 64
Ten-item Short Form Health Survey for Children (SF-10) physical domain scores to examine health-related Quality of Life
The SF-10 is a brief, 10-item, guardian-completed assessment designed to measure the physical and psychosocial functioning of children. The physical functioning (PHS) domain includes 5 questions that assess limitations in physical activities because of health problems. The PHS domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
Time frame: Weeks 0, 24, 40 and 64
Ten-item Short Form Health Survey for Children (SF-10) Psychosocial scores to examine health-related Quality of Life
The SF-10 is a brief, 10-item, guardian-completed assessment designed to measure the physical and psychosocial functioning of children. The Psychosocial functioning (PSS) domain includes 5 questions that assess limitations in psychosocial activities because of health problems. The PHS domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
Time frame: Weeks 0, 24, 40 and 64
Face Pain Scale-Revised (FPS-R) scores to examine health-related Quality of Life
The FPS-R is a dimensionless 10 point Likert scale used to assess self-reported pain intensity on a scale from 0 (no pain) to 10 (most pain you can imagine). Greater pain scores are indicative of more severe pain.
Time frame: Weeks 0, 24, 40 and 64
Patient-Reported Outcomes Measurement Information System (PROMIS) scores to examine health-related Quality of Life
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 Pain Interference Domain, decreases indicate less pain, for the Physical Function Mobility Domain, increases indicate greater mobility and for the Fatigue Domain, decreases indicate less fatigue.
Time frame: Weeks 0, 24, 40 and 64