A Phase 2 interventional study of Burosumab in Tumor Induced Osteomalacia (TIO) and Epidermal Nevus Syndrome (ENS), sponsored by Kyowa Kirin, Inc.. Completed at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-05-06.
Sponsored by Kyowa Kirin, Inc. · Phase 2, Interventional, and Treatment
The primary objectives of this study are to evaluate the effect of burosumab treatment on:
Exclusion Criteria:
Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.
Biological: Burosumab
Solution for subcutaneous injection
Also known as: KRN23, Crysvita®, UX023
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above 2.5 mg/dL at the Mid-Point of the Dose Intervals Between Baseline and Week 24
The percentage of participants achieving mean serum phosphorus levels above the lower limit of normal (LLN; 2.5 mg/dL \[0.81 mmol/L\]) at the mid-point of the dose interval (2 weeks after dosing), as averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
Time frame: Mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22 [there was no study visit at Week 18])
Change From Baseline to Week 48 in Osteoid Thickness
Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid thickness is the mean thickness of osteoid seams.
Time frame: Baseline, Week 48
Change From Baseline to Week 48 in Osteoid Surface/Bone Surface (OS/BS)
Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid surface/bone surface is expressed as the percentage of bone surface covered in osteoid.
Time frame: Baseline, Week 48
Change From Baseline to Week 48 in Osteoid Volume/Bone Volume (OV/BV)
Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid volume/bone volume is expressed as the percentage of a given volume of bone tissue that consists of unmineralized bone (osteoid).
Time frame: Baseline, Week 48
Change From Baseline to Week 48 in Mineralization Lag Time (MLt)
Mineralization lag time is a dynamic modeling parameter representing the mean time interval between the formation of osteoid and its subsequent mineralization which can be measured using histomorphometry with double tetracycline labeling. Mlt was calculated by dividing the osteoid width by the mineralizing apposition rate (MAR; the average rate at which new bone mineral is being added on any actively forming surface). If Mlt could not be calculated directly due to low tetracycline uptake, Mlt was imputed according to the following: Mlt = O.Th/(MAR\*MS/OS), where O.Th = osteoid thickness, MAR is imputed as 0.3 μm/day, MS/OS=mineralizing surface/osteoid surface, each measured at the same visit.
Time frame: Baseline, Week 48
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above 2.5 mg/dL at the End of the Dose Intervals Between Baseline and Week 24
The percentage of participants achieving mean serum phosphorus levels above the lower limit of normal (2.5 mg/dL \[0.81 mmol/L\]) at the end of the dose interval (4 weeks post-dose, prior to the next dose), as averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
Time frame: End of each dose interval from Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, and 24)
Mean Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
Mean change from Baseline to the mid-point of the dose interval (2 weeks after dosing) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
Time frame: Baseline and the mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22)
Percent Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
Mean percent change from Baseline to the mid-point of the dose interval (2 weeks after dosing) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
Time frame: Baseline and the mid-point of each dose interval from Baseline to Week 24 (Weeks 2, 6, 10, 14 and 22)
Mean Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Mean change from Baseline at the end of the dose interval (4 weeks post-dose, prior to the next dose) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Percent Mean Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Mean percent change from Baseline at the end of the dose interval (4 weeks post-dose, prior to the next dose) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Levels Between Baseline and Week 24
Serum phosphorus level versus time AUC was calculated using the trapezoidal rule. Time-adjusted AUC was calculated by dividing the AUC by duration of time included in AUC calculation.
Time frame: Pre-dose on Day 1 and at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 21, 22, and 24
Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration
Least squares (LS) means and standard errors (SE) were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 1,25(OH)2D, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration
Total FGF23 included free FGF23 and FGF23 bound to burosumab. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline total FGF23, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline free FGF23, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 24-hour Urinary Phosphorus
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 24-hour urinary phosphorus, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP)
Tubular reabsorption of phosphate (TRP) is the fraction of filtered phosphorus that is reabsorbed by renal tubules. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline TRP, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR)
TmP/GFR measures renal phosphate reabsorption (the primary mechanism by which FGF23 regulates phosphate homeostasis) by comparing the fractional absorption of phosphate relative to the estimated rate of glomerular filtration. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline TmP/GFR, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP)
FEP is the percentage of phosphorus filtered by the kidney that is excreted into urine, calculated as 100% \* (2-hour urine phosphorus\*serum creatinine)/(2-hour urine creatinine \* serum phosphorus). Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline FEP, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP)
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline ALP, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP)
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BALP, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Percent Change From Baseline Over Time in BALP
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BALP, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx)
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline CTx, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Percent Change From Baseline Over Time in CTx
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline CTx, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP)
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline P1NP, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Percent Change From Baseline Over Time in P1NP
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline P1NP, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Osteocalcin
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline osteocalcin, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Percent Change From Baseline Over Time in Osteocalcin
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline osteocalcin, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Elbow Measurements
To assess muscle strength, hand-held dynamometry was conducted using a standardized technique. Bilateral strength (defined as the average of the left and the right scores, measured in kilograms) of the elbow flexors and extensors was measured by the maximum voluntary isometric contraction against a dynamometer. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline strength measurements, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24 and 48
Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Knee Measurements
To assess muscle strength, hand-held dynamometry was conducted using a standardized technique. Bilateral strength (defined as the average of the left and the right scores, measured in kilograms) of the knee flexors and extensors was measured by the maximum voluntary isometric contraction against a dynamometer. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline strength measurements, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24 and 48
Change From Baseline Over Time in Sit-to-Stand (STS) Test
The STS test measures lower extremity strength and mobility as a participant moves repeatedly from a seated position to standing. This study used a modified STS test that allowed participants to use the arms of the chair to help them stand and sit if necessary. The number of sit-to-stand repetitions performed in a 30-second period was recorded. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24 and 48
Change From Baseline Over Time in Weighted Arm Lift (WAL) Test
The Weighted arm lift (WAL) test assesses upper extremity strength, mobility and reaching ability. The test was administered bilaterally to determine the number of times the participant could raise a 1 kg weight above the head in a 30-second period. The number of repetitions completed with each arm was recorded. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline WAL measurements, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24 and 48
Change From Baseline Over Time in Six-Minute Walk Test (6MWT)
The 6MWT is a commonly used measure of mobility and was conducted in accordance with general principles set forth in the American Thoracic Society guidelines (ATS 2002). Participants were instructed to walk the length of a pre-measured course for 6 consecutive minutes (assistive devices could be used). The total distance walked at the end of 6 minutes was recorded in meters. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 6MWT measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24 and 48
Change From Baseline Over Time in Brief Pain Inventory (BPI) Worst Pain Score
The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Worst pain is defined as the answer to Question 3, in which participants rated their pain at its worst in the last 24 hours on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Severity Score
The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Pain severity is defined as the average of 4 questions (Questions 3 through 6) assessing worst pain, least pain, average pain, and pain right now, rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). Mild pain is defined as a score of 1 to 4, moderate pain is defined as a score of 5 to 6, and severe pain is defined as a score of 7 to 10. A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Brief Pain Inventory (BPI) Pain Interference Score
The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Pain interference is defined as the average of 7 questions (9A through 9G) regarding the extent to which pain interfered with daily activities, including general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Worst Fatigue Score
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Worst fatigue is defined as the answer to Question 3 in which participants rated their fatigue at its worst in the last 24 hours on a scale from 0 (no fatigue) to 10 (as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Severity Score
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Fatigue severity is defined as the average of 3 questions (Questions 1 through 3) assessing fatigue right now, usual level of fatigue, and worst fatigue, rated on a scale from 0 (no fatigue) to 10 (as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Fatigue Interference Score
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. The fatigue interference score is defined as the average of 6 questions (Questions 4A through 4F) regarding the extent to which fatigue interfered with daily activities, including general activity, mood, walking ability, work, relations with others, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in Brief Fatigue Inventory (BFI) Global Fatigue Score
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. The first 3 questions measure fatigue severity and the next 6 questions assess the impact of fatigue on daily activities. The global fatigue score is defined as the average of all 9 questions on the BFI including severity and interference, and ranges from from 0 to 10, where higher scores correspond to greater levels of fatigue. A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary score (PCS) is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance struct
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Physical Functioning Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning (PF) domain includes 10 questions that assess limitations in physical activities because of health problems. The PF 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Physical Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The role-physical (RP) domain includes 4 questions that assess limitations in usual role activities because of physical health problems. The RP 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Bodily Pain Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The bodily pain (BP) domain includes 2 questions that assess pain level and impact of pain on normal work. The BP 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) General Health Perceptions Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The general health perceptions (GH) domain includes 5 questions that assess participants' perception of their own general health. The GH 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Component Summary Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The mental component summary score (MCS) is a weighted combination of the 8 subscales with positive weighting for vitality, social function, role limitations due to emotional problems, and mental health. The MCS 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 indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Vitality Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The vitality (VT) domain includes 4 questions that assess energy levels and fatigue. The VT 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Social Functioning Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The social functioning (SF) domain includes 2 questions that assess limitations in social activities because of physical health or emotional problems. The SF 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Role Emotional Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The role-emotional (RE) domain includes 3 questions that assess limitations in usual role activities because of emotional problems. The RE 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) Mental Health Domain Score
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The mental health (MH) domain includes 5 questions that assess general mental health (psychological distress and well-being). The MH 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
Time frame: Baseline and Weeks 24, 48, 96, 144, 168, 192, 216, and 240
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. A serious AE was defined as an AE that at any dose, in the view of either the Investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or disability, a congenital anomaly/birth defect, or other important medical events (according to the investigator). An AE was considered a TEAE if it occurred on or after the first dose and was not present prior to the first dose, or it was present prior to the first dose but increased in severity during the study. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).
Time frame: From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
Number of Participants With Anti-burosumab Antibodies
Time frame: From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.
This study was conducted at 8 centers in the United States, and enrolled adults with tumor-induced osteomalacia (TIO), epidermal nevus syndrome (ENS)-associated osteomalacia, or x-linked hypophosphatemia (XLH).
| Milestone | Burosumab |
|---|---|
| Started | 17 |
| Completed 48 weeks of study drug | 16 |
| Completed 144 weeks of study drug | 12 |
| Completed | 9 |
| Not completed | 8 |
| Withdrew: Lack of response to bruosumab | 1 |
| Withdrew: Sponsor decision | 3 |
| Withdrew: Death | 2 |
| Withdrew: Physician decision | 1 |
| Withdrew: Unable to return due to corona virus pandemic | 1 |
The percentage of participants achieving mean serum phosphorus levels above the lower limit of normal (LLN; 2.5 mg/dL \[0.81 mmol/L\]) at the mid-point of the dose interval (2 weeks after dosing), as averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
| percentage of participants | Burosumab |
|---|---|
| Percentage of Participants Achieving Mean Serum Phosphorus Levels Above 2.5 mg/dL at the Mid-Point of the Dose Intervals Between Baseline and Week 24 | 50.0 (26.80 to 73.20) |
Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid thickness is the mean thickness of osteoid seams.
| µm | Burosumab |
|---|---|
| Change From Baseline to Week 48 in Osteoid Thickness | -5.12 (-10.04 to -0.20) |
Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid surface/bone surface is expressed as the percentage of bone surface covered in osteoid.
| percentage of bone surface | Burosumab |
|---|---|
| Change From Baseline to Week 48 in Osteoid Surface/Bone Surface (OS/BS) | -0.18 (-13.86 to 13.50) |
Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader. Osteoid volume/bone volume is expressed as the percentage of a given volume of bone tissue that consists of unmineralized bone (osteoid).
| percentage of bone volume | Burosumab |
|---|---|
| Change From Baseline to Week 48 in Osteoid Volume/Bone Volume (OV/BV) | -5.47 (-11.87 to 0.93) |
Mineralization lag time is a dynamic modeling parameter representing the mean time interval between the formation of osteoid and its subsequent mineralization which can be measured using histomorphometry with double tetracycline labeling. Mlt was calculated by dividing the osteoid width by the mineralizing apposition rate (MAR; the average rate at which new bone mineral is being added on any actively forming surface). If Mlt could not be calculated directly due to low tetracycline uptake, Mlt was imputed according to the following: Mlt = O.Th/(MAR\*MS/OS), where O.Th = osteoid thickness, MAR is imputed as 0.3 μm/day, MS/OS=mineralizing surface/osteoid surface, each measured at the same visit.
| days | Burosumab |
|---|---|
| Change From Baseline to Week 48 in Mineralization Lag Time (MLt) | -565.20 (-2037.42 to 907.02) |
The percentage of participants achieving mean serum phosphorus levels above the lower limit of normal (2.5 mg/dL \[0.81 mmol/L\]) at the end of the dose interval (4 weeks post-dose, prior to the next dose), as averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
| percentage of participants | Burosumab |
|---|---|
| Percentage of Participants Achieving Mean Serum Phosphorus Levels Above 2.5 mg/dL at the End of the Dose Intervals Between Baseline and Week 24 | 21.4 (7.57 to 47.59) |
Mean change from Baseline to the mid-point of the dose interval (2 weeks after dosing) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
| mg/dL | Burosumab |
|---|---|
| Mean Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 | 1.039 ± 0.5622 |
Mean percent change from Baseline to the mid-point of the dose interval (2 weeks after dosing) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 2, 6, 10, 14 and 22).
| percent change | Burosumab |
|---|---|
| Percent Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 | 69.77 ± 43.743 |
Mean change from Baseline at the end of the dose interval (4 weeks post-dose, prior to the next dose) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
| mg/dL | Burosumab |
|---|---|
| Mean Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 0.550 ± 0.4260 |
Mean percent change from Baseline at the end of the dose interval (4 weeks post-dose, prior to the next dose) averaged across dose cycles between Baseline and Week 24 (i.e. the average of serum phosphorus levels at Weeks 4, 8, 12, 16, 20, and 24).
| percent change | Burosumab |
|---|---|
| Percent Mean Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 38.56 ± 33.027 |
Serum phosphorus level versus time AUC was calculated using the trapezoidal rule. Time-adjusted AUC was calculated by dividing the AUC by duration of time included in AUC calculation.
| mg/dL | Burosumab |
|---|---|
| Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Levels Between Baseline and Week 24 | 2.36 ± 0.632 |
Least squares (LS) means and standard errors (SE) were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 1,25(OH)2D, with compound symmetry covariance structure.
| pg/mL | Burosumab |
|---|---|
| Week 24 | 9.90 ± 4.10 |
| Week 48 | 10.49 ± 4.82 |
| Week 96 | 4.28 ± 3.80 |
| Week 144 | 3.15 ± 3.34 |
| Week 168 | 4.91 ± 3.94 |
| Week 192 | 0.67 ± 4.19 |
| Week 216 | 9.78 ± 3.04 |
| Week 240 | 6.56 ± 3.19 |
Total FGF23 included free FGF23 and FGF23 bound to burosumab. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline total FGF23, with compound symmetry covariance structure.
| pg/mL | Burosumab |
|---|---|
| Week 24 | 246335.35 ± 61089.98 |
| Week 48 | 180511.74 ± 33529.14 |
| Week 96 | 331267.40 ± 103226.37 |
| Week 144 | 275758.40 ± 102349.79 |
| Week 168 | 185769.23 ± 65423.93 |
| Week 192 | 234826.20 ± 82198.24 |
| Week 216 | 254359.96 ± 81615.67 |
| Week 240 | 210119.10 ± 76610.50 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline free FGF23, with compound symmetry covariance structure.
| pg/mL | Burosumab |
|---|---|
| Week 24 | 624.91 ± 101.89 |
| Week 48 | 578.07 ± 95.37 |
| Week 96 | 736.59 ± 139.18 |
| Week 144 | 801.69 ± 103.41 |
| Week 168 | 787.16 ± 95.52 |
| Week 192 | 717.71 ± 115.99 |
| Week 216 | 704.87 ± 115.30 |
| Week 240 | 625.16 ± 125.93 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 24-hour urinary phosphorus, with compound symmetry covariance structure.
| mg/dL | Burosumab |
|---|---|
| Week 24 | -3.66 ± 8.28 |
| Week 48 | 3.59 ± 6.73 |
| Week 96 | 3.22 ± 6.40 |
| Week 144 | 3.25 ± 6.971 |
| Week 168 | 4.98 ± 8.18 |
| Week 192 | 8.31 ± 4.54 |
| Week 216 | 13.93 ± 14.30 |
| Week 240 | 13.11 ± 9.35 |
Tubular reabsorption of phosphate (TRP) is the fraction of filtered phosphorus that is reabsorbed by renal tubules. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline TRP, with compound symmetry covariance structure.
| fraction of phosphorus reabsorbed | Burosumab |
|---|---|
| Week 24 | 0.13 ± 0.02 |
| Week 48 | 0.14 ± 0.02 |
| Week 96 | 0.10 ± 0.03 |
| Week 144 | 0.13 ± 0.02 |
| Week 168 | 0.12 ± 0.02 |
| Week 192 | 0.14 ± 0.02 |
| Week 216 | 0.14 ± 0.01 |
| Week 240 | 0.12 ± 0.02 |
TmP/GFR measures renal phosphate reabsorption (the primary mechanism by which FGF23 regulates phosphate homeostasis) by comparing the fractional absorption of phosphate relative to the estimated rate of glomerular filtration. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline TmP/GFR, with compound symmetry covariance structure.
| mg/dL | Burosumab |
|---|---|
| Week 24 | 0.81 ± 0.13 |
| Week 48 | 0.88 ± 0.14 |
| Week 96 | 0.73 ± 0.23 |
| Week 144 | 0.13 ± 0.02 |
| Week 168 | 1.07 ± 0.29 |
| Week 192 | 0.95 ± 0.16 |
| Week 216 | 0.88 ± 0.12 |
| Week 240 | 0.94 ± 0.15 |
FEP is the percentage of phosphorus filtered by the kidney that is excreted into urine, calculated as 100% \* (2-hour urine phosphorus\*serum creatinine)/(2-hour urine creatinine \* serum phosphorus). Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline FEP, with compound symmetry covariance structure.
| percentage of phosphorus | Burosumab |
|---|---|
| Week 24 | -0.14 ± 0.02 |
| Week 48 | -0.14 ± 0.02 |
| Week 96 | -0.10 ± 0.03 |
| Week 144 | -0.15 ± 0.02 |
| Week 168 | -0.14 ± 0.02 |
| Week 192 | -0.14 ± 0.02 |
| Week 216 | -0.15 ± 0.01 |
| Week 240 | -0.14 ± 0.02 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline ALP, with compound symmetry covariance structure.
| U/L | Burosumab |
|---|---|
| Week 24 | -1.68 ± 10.91 |
| Week 48 | -20.36 ± 11.68 |
| Week 96 | -38.23 ± 11.90 |
| Week 144 | -57.45 ± 10.97 |
| Week 168 | -62.80 ± 12.35 |
| Week 192 | -60.40 ± 12.41 |
| Week 216 | -50.14 ± 26.09 |
| Week 240 | -49.71 ± 24.35 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BALP, with compound symmetry covariance structure.
| μg/L | Burosumab |
|---|---|
| Week 24 | -1.13 ± 4.87 |
| Week 48 | -9.65 ± 4.74 |
| Week 96 | -15.89 ± 4.27 |
| Week 144 | -19.81 ± 4.42 |
| Week 168 | -22.05 ± 4.52 |
| Week 192 | -21.54 ± 4.87 |
| Week 216 | -15.50 ± 11.39 |
| Week 240 | -21.58 ± 6.17 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BALP, with compound symmetry covariance structure.
| percent change | Burosumab |
|---|---|
| Week 24 | 5.15 ± 13.06 |
| Week 48 | -16.56 ± 8.35 |
| Week 96 | -30.40 ± 8.57 |
| Week 144 | -35.82 ± 9.47 |
| Week 168 | -40.97 ± 9.60 |
| Week 192 | -41.11 ± 9.93 |
| Week 216 | -28.41 ± 20.71 |
| Week 240 | -42.27 ± 11.65 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline CTx, with compound symmetry covariance structure.
| pg/mL | Burosumab |
|---|---|
| Week 24 | 212.91 ± 125.76 |
| Week 48 | 97.02 ± 80.10 |
| Week 96 | 6.55 ± 63.66 |
| Week 144 | -19.28 ± 38.49 |
| Week 168 | -100.84 ± 49.31 |
| Week 192 | -200.40 ± 65.80 |
| Week 216 | -140.71 ± 94.55 |
| Week 240 | -92.14 ± 102.27 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline CTx, with compound symmetry covariance structure.
| percent change | Burosumab |
|---|---|
| Week 24 | 33.77 ± 14.33 |
| Week 48 | 31.05 ± 20.220 |
| Week 96 | 11.96 ± 12.05 |
| Week 144 | 10.92 ± 8.86 |
| Week 168 | -2.23 ± 8.29 |
| Week 192 | -15.90 ± 11.21 |
| Week 216 | -10.53 ± 7.40 |
| Week 240 | -5.68 ± 10.26 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline P1NP, with compound symmetry covariance structure.
| ng/mL | Burosumab |
|---|---|
| Week 24 | 34.07 ± 10.90 |
| Week 48 | 7.73 ± 7.05 |
| Week 96 | 11.28 ± 15.56 |
| Week 144 | 1.21 ± 5.55 |
| Week 168 | -12.04 ± 3.36 |
| Week 192 | -11.93 ± 8.11 |
| Week 216 | -7.53 ± 14.58 |
| Week 240 | -1.67 ± 14.39 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline P1NP, with compound symmetry covariance structure.
| percent change | Burosumab |
|---|---|
| Week 24 | 53.71 ± 16.35 |
| Week 48 | 15.64 ± 10.84 |
| Week 96 | 18.09 ± 20.29 |
| Week 144 | 13.65 ± 8.68 |
| Week 168 | -12.40 ± 4.98 |
| Week 192 | 0.93 ± 19.78 |
| Week 216 | -7.58 ± 17.45 |
| Week 240 | 4.47 ± 16.82 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline osteocalcin, with compound symmetry covariance structure.
| ng/mL | Burosumab |
|---|---|
| Week 24 | 9.51 ± 4.85 |
| Week 48 | 2.20 ± 3.48 |
| Week 96 | -0.54 ± 2.75 |
| Week 144 | -0.52 ± 1.89 |
| Week 168 | -3.14 ± 1.35 |
| Week 192 | -6.91 ± 2.49 |
| Week 216 | -7.97 ± 5.35 |
| Week 240 | -8.55 ± 5.22 |
Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline osteocalcin, with compound symmetry covariance structure.
| percent change | Burosumab |
|---|---|
| Week 24 | 41.49 ± 12.19 |
| Week 48 | 16.28 ± 13.79 |
| Week 96 | 15.04 ± 14.10 |
| Week 144 | 14.08 ± 8.38 |
| Week 168 | -0.98 ± 7.11 |
| Week 192 | -19.67 ± 10.42 |
| Week 216 | -5.65 ± 11.48 |
| Week 240 | -8.37 ± 10.17 |
To assess muscle strength, hand-held dynamometry was conducted using a standardized technique. Bilateral strength (defined as the average of the left and the right scores, measured in kilograms) of the elbow flexors and extensors was measured by the maximum voluntary isometric contraction against a dynamometer. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline strength measurements, with compound symmetry covariance structure.
| kg | Elbow Flexion | Elbow Extension |
|---|---|---|
| Week 24 | 0.12 ± 0.512 | 0.75 ± 0.704 |
| Week 48 | 0.32 ± 0.753 | 1.06 ± 0.760 |
To assess muscle strength, hand-held dynamometry was conducted using a standardized technique. Bilateral strength (defined as the average of the left and the right scores, measured in kilograms) of the knee flexors and extensors was measured by the maximum voluntary isometric contraction against a dynamometer. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline strength measurements, with compound symmetry covariance structure.
| kg | Knee Flexion | Knee Extension |
|---|---|---|
| Week 24 | 0.94 ± 1.139 | -0.89 ± 1.573 |
| Week 48 | 1.21 ± 1.297 | 0.75 ± 1.158 |
The STS test measures lower extremity strength and mobility as a participant moves repeatedly from a seated position to standing. This study used a modified STS test that allowed participants to use the arms of the chair to help them stand and sit if necessary. The number of sit-to-stand repetitions performed in a 30-second period was recorded. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline measurement, with compound symmetry covariance structure.
| sit-to-stand repetitions | Burosumab |
|---|---|
| Week 24 | 1.5 ± 0.54 |
| Week 48 | 1.6 ± 0.50 |
The Weighted arm lift (WAL) test assesses upper extremity strength, mobility and reaching ability. The test was administered bilaterally to determine the number of times the participant could raise a 1 kg weight above the head in a 30-second period. The number of repetitions completed with each arm was recorded. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline WAL measurements, with compound symmetry covariance structure.
| arm lifts | Left Upper Extremity | Right Upper Extremity |
|---|---|---|
| Week 24 | -0.5 ± 1.09 | 0.6 ± 0.89 |
| Week 48 | 0.1 ± 1.25 | 1.7 ± 1.17 |
The 6MWT is a commonly used measure of mobility and was conducted in accordance with general principles set forth in the American Thoracic Society guidelines (ATS 2002). Participants were instructed to walk the length of a pre-measured course for 6 consecutive minutes (assistive devices could be used). The total distance walked at the end of 6 minutes was recorded in meters. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline 6MWT measurement, with compound symmetry covariance structure.
| meters | Burosumab |
|---|---|
| Week 24 | 19.5 ± 15.64 |
| Week 48 | 25.5 ± 16.58 |
The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Worst pain is defined as the answer to Question 3, in which participants rated their pain at its worst in the last 24 hours on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -0.6 ± 0.7 |
| Week 48 | -0.9 ± 0.7 |
| Week 96 | -0.7 ± 0.4 |
| Week 144 | -1.1 ± 0.6 |
| Week 168 | -0.9 ± 0.7 |
| Week 192 | -0.9 ± 0.6 |
| Week 216 | -0.9 ± 0.8 |
| Week 240 | -0.9 ± 0.9 |
The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Pain severity is defined as the average of 4 questions (Questions 3 through 6) assessing worst pain, least pain, average pain, and pain right now, rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). Mild pain is defined as a score of 1 to 4, moderate pain is defined as a score of 5 to 6, and severe pain is defined as a score of 7 to 10. A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -0.51 ± 0.62 |
| Week 48 | -0.87 ± 0.66 |
| Week 96 | -0.62 ± 0.38 |
| Week 144 | -0.99 ± 0.42 |
| Week 168 | -1.21 ± 0.40 |
| Week 192 | -0.81 ± 0.66 |
| Week 216 | -0.75 ± 0.63 |
| Week 240 | -0.91 ± 0.76 |
The Brief Pain Inventory (BPI) is a self-reported, pain-specific questionnaire with a recall period of 24 hours. Pain interference is defined as the average of 7 questions (9A through 9G) regarding the extent to which pain interfered with daily activities, including general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BPI measurement, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -1.15 ± 0.66 |
| Week 48 | -1.09 ± 0.80 |
| Week 96 | -1.08 ± 0.55 |
| Week 144 | -1.46 ± 0.61 |
| Week 168 | -1.76 ± 0.37 |
| Week 192 | -1.11 ± 0.58 |
| Week 216 | -1.56 ± 0.87 |
| Week 240 | -2.00 ± 1.10 |
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Worst fatigue is defined as the answer to Question 3 in which participants rated their fatigue at its worst in the last 24 hours on a scale from 0 (no fatigue) to 10 (as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -1.3 ± 0.5 |
| Week 48 | -0.9 ± 0.8 |
| Week 96 | -1.0 ± 0.5 |
| Week 144 | -0.9 ± 0.6 |
| Week 168 | -1.6 ± 0.6 |
| Week 192 | -1.0 ± 0.4 |
| Week 216 | -2.1 ± 0.9 |
| Week 240 | -2.6 ± 0.9 |
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. Fatigue severity is defined as the average of 3 questions (Questions 1 through 3) assessing fatigue right now, usual level of fatigue, and worst fatigue, rated on a scale from 0 (no fatigue) to 10 (as bad as you can imagine). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -1.47 ± 0.53 |
| Week 48 | -1.31 ± 0.56 |
| Week 96 | -1.58 ± 0.43 |
| Week 144 | -1.44 ± 0.53 |
| Week 168 | -2.34 ± 0.43 |
| Week 192 | -1.62 ± 0.43 |
| Week 216 | -2.62 ± 0.85 |
| Week 240 | -2.57 ± 0.81 |
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. The fatigue interference score is defined as the average of 6 questions (Questions 4A through 4F) regarding the extent to which fatigue interfered with daily activities, including general activity, mood, walking ability, work, relations with others, and enjoyment of life in the last 24 hours, rated on a scale from 0 (does not interfere) to 10 (completely interferes). A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -1.57 ± 0.65 |
| Week 48 | -1.88 ± 0.66 |
| Week 96 | -1.98 ± 0.47 |
| Week 144 | -1.67 ± 0.44 |
| Week 168 | -2.20 ± 0.38 |
| Week 192 | -1.24 ± 0.59 |
| Week 216 | -2.72 ± 1.02 |
| Week 240 | -3.00 ± 1.14 |
The Brief Fatigue Inventory (BFI) is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a 0 to 10 numerical rating scale with a recall period of 24 hours. The first 3 questions measure fatigue severity and the next 6 questions assess the impact of fatigue on daily activities. The global fatigue score is defined as the average of all 9 questions on the BFI including severity and interference, and ranges from from 0 to 10, where higher scores correspond to greater levels of fatigue. A negative change from Baseline score indicates improvement. Least squares means and standard errors were estimated from a generalized estimation equation (GEE) model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline BFI measurement, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -1.54 ± 0.56 |
| Week 48 | -1.66 ± 0.56 |
| Week 96 | -1.83 ± 0.44 |
| Week 144 | -1.58 ± 0.44 |
| Week 168 | -2.23 ± 0.37 |
| Week 192 | -1.34 ± 0.50 |
| Week 216 | -2.66 ± 0.95 |
| Week 240 | -2.83 ± 1.02 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary score (PCS) is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance struct
| score on a scale | Burosumab |
|---|---|
| Week 24 | 3.71 ± 1.42 |
| Week 48 | 5.43 ± 2.33 |
| Week 96 | 2.75 ± 1.37 |
| Week 144 | 7.98 ± 2.40 |
| Week 168 | 5.20 ± 2.14 |
| Week 192 | 3.82 ± 2.49 |
| Week 216 | 6.17 ± 2.17 |
| Week 240 | 5.82 ± 2.45 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning (PF) domain includes 10 questions that assess limitations in physical activities because of health problems. The PF 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 2.29 ± 1.58 |
| Week 48 | 2.63 ± 2.51 |
| Week 96 | 3.77 ± 1.58 |
| Week 144 | 7.89 ± 2.00 |
| Week 168 | 5.50 ± 2.24 |
| Week 192 | 3.02 ± 2.04 |
| Week 216 | 6.75 ± 1.96 |
| Week 240 | 4.56 ± 3.11 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The role-physical (RP) domain includes 4 questions that assess limitations in usual role activities because of physical health problems. The RP 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 4.85 ± 1.74 |
| Week 48 | 5.00 ± 2.83 |
| Week 96 | 3.25 ± 1.63 |
| Week 144 | 5.53 ± 2.81 |
| Week 168 | 5.70 ± 1.93 |
| Week 192 | 5.03 ± 2.80 |
| Week 216 | 4.82 ± 3.01 |
| Week 240 | 8.99 ± 3.28 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The bodily pain (BP) domain includes 2 questions that assess pain level and impact of pain on normal work. The BP 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 1.61 ± 1.65 |
| Week 48 | 3.61 ± 1.48 |
| Week 96 | 2.52 ± 1.08 |
| Week 144 | 5.40 ± 1.90 |
| Week 168 | 5.01 ± 2.16 |
| Week 192 | 4.92 ± 2.81 |
| Week 216 | 6.64 ± 1.88 |
| Week 240 | 6.59 ± 2.20 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The general health perceptions (GH) domain includes 5 questions that assess participants' perception of their own general health. The GH 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 2.38 ± 1.88 |
| Week 48 | 6.09 ± 2.28 |
| Week 96 | 1.03 ± 1.96 |
| Week 144 | 3.12 ± 2.64 |
| Week 168 | -0.32 ± 2.51 |
| Week 192 | -1.60 ± 2.94 |
| Week 216 | -1.51 ± 2.05 |
| Week 240 | 1.81 ± 3.30 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The mental component summary score (MCS) is a weighted combination of the 8 subscales with positive weighting for vitality, social function, role limitations due to emotional problems, and mental health. The MCS 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 indicates an improvement. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 1.07 ± 2.38 |
| Week 48 | 1.37 ± 2.47 |
| Week 96 | 3.91 ± 2.53 |
| Week 144 | -0.85 ± 2.29 |
| Week 168 | 2.05 ± 1.81 |
| Week 192 | 0.55 ± 2.95 |
| Week 216 | 0.51 ± 2.67 |
| Week 240 | 5.13 ± 3.59 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The vitality (VT) domain includes 4 questions that assess energy levels and fatigue. The VT 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 5.98 ± 1.96 |
| Week 48 | 5.27 ± 2.42 |
| Week 96 | 6.71 ± 2.64 |
| Week 144 | 3.05 ± 2.30 |
| Week 168 | 6.04 ± 2.74 |
| Week 192 | 2.78 ± 2.85 |
| Week 216 | 6.79 ± 3.77 |
| Week 240 | 8.06 ± 4.03 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The social functioning (SF) domain includes 2 questions that assess limitations in social activities because of physical health or emotional problems. The SF 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 2.02 ± 2.24 |
| Week 48 | 5.54 ± 2.48 |
| Week 96 | 4.63 ± 1.34 |
| Week 144 | 3.22 ± 2.71 |
| Week 168 | 5.34 ± 2.06 |
| Week 192 | 2.84 ± 2.62 |
| Week 216 | 4.15 ± 2.08 |
| Week 240 | 6.30 ± 2.98 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The role-emotional (RE) domain includes 3 questions that assess limitations in usual role activities because of emotional problems. The RE 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | 1.52 ± 1.98 |
| Week 48 | 1.13 ± 2.72 |
| Week 96 | 6.73 ± 3.03 |
| Week 144 | 2.10 ± 2.60 |
| Week 168 | 4.90 ± 2.22 |
| Week 192 | 3.51 ± 3.47 |
| Week 216 | 3.56 ± 3.08 |
| Week 240 | 6.04 ± 3.69 |
The SF-36 v2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The mental health (MH) domain includes 5 questions that assess general mental health (psychological distress and well-being). The MH 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. LS means and SEs were estimated from a GEE model which includes the change from Baseline as the dependent variable, time as the categorical variable and adjusted for Baseline SF-36, with compound symmetry covariance structure.
| score on a scale | Burosumab |
|---|---|
| Week 24 | -0.46 ± 2.54 |
| Week 48 | -0.32 ± 2.48 |
| Week 96 | -0.58 ± 2.12 |
| Week 144 | -0.17 ± 1.97 |
| Week 168 | -0.97 ± 1.61 |
| Week 192 | -1.24 ± 2.23 |
| Week 216 | -2.11 ± 2.87 |
| Week 240 | 3.50 ± 3.10 |
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. A serious AE was defined as an AE that at any dose, in the view of either the Investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or disability, a congenital anomaly/birth defect, or other important medical events (according to the investigator). An AE was considered a TEAE if it occurred on or after the first dose and was not present prior to the first dose, or it was present prior to the first dose but increased in severity during the study. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).
| Participants | Burosumab |
|---|---|
| Any adverse event | 14 |
| Serious adverse events (SAEs) | 8 |
| Related adverse events | 9 |
| Serious related adverse events | 0 |
| Grade 3 or 4 adverse event | 8 |
| TEAE leading to study discontinuation | 0 |
| TEAE leading to treatment discontinuation | 1 |
| TEAE leading to death | 2 |
| Participants | Burosumab |
|---|---|
| Anti-burosumab binding antibodies | 2 |
| Anti-burosumab neutralizing antibodies | 0 |
Collected over From first dose of study drug up to database lock date (July 07, 2021); median duration of treatment in the TIO analysis set was 1594.0 (range: 168-2106) days.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| KRN23 TIO | 2/14 (14.3%) | 8/14 (57.1%) | 14/14 (100%) |
| KRN23 XLH and ENS | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Event | KRN23 TIO | KRN23 XLH and ENS |
|---|---|---|
| Neoplasm ProgressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 4/14 | 0/3 |
| Cardiac ArrestCardiac disorders | 2/14 | 0/3 |
| Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders | 2/14 | 0/3 |
| Pulseless Electrical ActivityCardiac disorders | 1/14 | 0/3 |
| AscitesGastrointestinal disorders | 1/14 | 0/3 |
| PancreatitisGastrointestinal disorders | 1/14 | 0/3 |
| Multi-Organ FailureGeneral disorders | 1/14 | 0/3 |
| CholangitisHepatobiliary disorders | 1/14 | 0/3 |
| Septic ShockInfections and infestations | 1/14 | 0/3 |
| SialoadenitisInfections and infestations | 1/14 | 0/3 |
| Event | KRN23 TIO | KRN23 XLH and ENS |
|---|---|---|
| Musculoskeletal PainMusculoskeletal and connective tissue disorders | 4/14 | 2/3 |
| Pain In ExtremityMusculoskeletal and connective tissue disorders | 9/14 | 2/3 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 9/14 | 1/3 |
| Upper Respiratory Tract InfectionInfections and infestations | 7/14 | 1/3 |
| CoughRespiratory, thoracic and mediastinal disorders | 7/14 | 1/3 |
| DiarrhoeaGastrointestinal disorders | 6/14 | 0/3 |
| NauseaGastrointestinal disorders | 5/14 | 1/3 |
| VomitingGastrointestinal disorders | 5/14 | 1/3 |
| NasopharyngitisInfections and infestations | 5/14 | 1/3 |
| Back PainMusculoskeletal and connective tissue disorders | 5/14 | 0/3 |
All enrolled participants
| Age, Continuous(years) | Burosumab |
|---|---|
| Mean | 53.1 ± 13.86 |
| Sex: Female, Male(Participants) | Burosumab |
|---|---|
| Female | 8 |
| Male | 9 |
| Ethnicity (NIH/OMB)(Participants) | Burosumab |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 17 |
| Unknown or Not Reported | 0 |
| Race/Ethnicity, Customized(Participants) | Burosumab |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Black or African American | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| White | 15 |
| Other | 0 |
| Diagnosis(Participants) | Burosumab |
|---|---|
| Tumor-Induced osteomalacia (TIO) | 14 |
| Epidermal nevus syndrome-associated osteomalacia | 1 |
| X-linked hypophosphatemia (XLH) | 2 |
| Serum Total Fibroblast Growth Factor 23 (FGF23)(pg/mL) | Burosumab |
|---|---|
| Mean | 770.06 ± 797.654 |
| Serum Phosphorus(mg/dL) | Burosumab |
|---|---|
| Mean | 1.60 ± 0.474 |
| Osteoid Volume/Bone Volume (OB/BV)(percentage of bone volume) | Burosumab |
|---|---|
| Mean | 17.61 ± 19.485 |
3 further baseline measures are reported on the registry.
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Kyowa Kirin, Inc.