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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.

Burosumab

Medical Director

The primary objectives of this study are to evaluate the effect of burosumab treatment on:

* Increasing serum phosphorus levels in adults with TIO or ENS-associated osteomalacia
* Improvement in TIO/ENS-associated osteomalacia as determined by osteoid thickness (O.Th), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV) and mineralization lag time (MLt).

Study of Burosumab (KRN23) in Adults With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)

A Phase 2 Open-Label Trial to Assess the Efficacy and Safety of KRN23, an Antibody to FGF23, in Subjects With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)-Associated Osteomalacia

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).

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).

Histomorphometry of trans-iliac crest bone biopsies was assessed by a blinded, central reader.

Osteoid thickness is the mean thickness of osteoid seams.

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.

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).

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.

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).

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

Kyowa Kirin, Inc.

Participants with TIO 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.

KRN23 TIO

Participants with XLH and ENS 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.

KRN23 XLH and ENS

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Two participants who were enrolled in the study with a clinical diagnosis of TIO were later found to have X-linked hypophosphatemia (XLH) based on genetic testing.

Diagnosis

Tumor-induced osteomalacia (TIO) analysis set includes the 14 participants with TIO who received at least 1 dose of study drug.

Serum Total Fibroblast Growth Factor 23 (FGF23)

Serum Phosphorus

The percentage of a given volume of bone tissue that consists of unmineralized bone (osteoid).

TIO biopsy analysis set includes 11 participants with TIO who received at least 1 dose of study drug and who had paired bone biopsies at Baseline and Week 48.

Osteoid Volume/Bone Volume (OB/BV)

The percentage of bone surface covered in osteoid.

Osteoid Surface/Bone Surface (OS/BS)

Mean thickness, given in micrometers, for osteoid seams

Osteoid Thickness (O.Th)

Mineralization lag time is the average time interval between osteoid formation and its subsequent mineralization, 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.

TIO biopsy analysis set for whom Mlt could be calculated or imputed

Mineralization Lag Time (Mlt)

Medical Information

TIO analysis set: includes participants with TIO who received at least 1 dose of burosumab during the study.

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 null hypothesis that the mean change from Baseline to Week 48 in osteoid thickness is zero was tested using a t-test.

Change From Baseline to Week 48 in Osteoid Thickness

The null hypothesis that the mean change from Baseline to Week 48 in OS/BS is zero was tested using a t-test.

Change From Baseline to Week 48 in Osteoid Surface/Bone Surface (OS/BS)

The null hypothesis that the mean change from Baseline to Week 48 in OV/BV is zero was tested using a t-test.

Change From Baseline to Week 48 in Osteoid Volume/Bone Volume (OV/BV)

The null hypothesis that the mean change from Baseline to Week 48 in Mlt is zero was tested using a t-test.

Change From Baseline to Week 48 in Mineralization Lag Time (MLt)

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

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

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 Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 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

Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Levels Between Baseline and Week 24

Week 24

Week 48

Week 96

Week 144

Week 168

Week 192

Week 216

Week 240

TIO analysis set participants with available data at Baseline and each time point.

Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) Concentration

TIO analysis set with available data at each time point

Change From Baseline Over Time in Total Serum Fibroblast Growth Factor 23 (FGF23) Concentration

Change From Baseline Over Time in Free Serum Fibroblast Growth Factor 23 (FGF23) Concentration

TIO analysis set participants with available data at each time point.

Change From Baseline Over Time in 24-hour Urinary Phosphorus

Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP)

Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR)

Change From Baseline Over Time in Fractional Excretion of Phosphorus (FEP)

Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP)

Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP)

Percent Change From Baseline Over Time in BALP

TIO analysis set participants with available data at each time point

Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx)

Percent Change From Baseline Over Time in CTx

Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP)

Percent Change From Baseline Over Time in P1NP

Change From Baseline Over Time in Osteocalcin

Percent Change From Baseline Over Time in Osteocalcin

Elbow flexor (biceps brachii, brachioradialis, and brachialis) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.

Elbow Flexion

Elbow extensor (triceps brachii and anconeus) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.

Elbow Extension

TIO analysis set with available elbow dynamometry measurements at Baseline and each time point.

Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Elbow Measurements

Knee flexor (hamstring) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.

Knee Flexion

Knee extensor (quadriceps) muscle strength was measured in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W. Doses may have been titrated up to a maximum of 2.0 mg/kg Q2W.

Knee Extension

TIO analysis set with available knee dynamometry measurements at Baseline and each time point.

Change From Baseline Over Time in Hand-Held Dynamometry (HHD) Knee Measurements

TIO analysis set with available STS data at each time point; One participant did not perform the test at Baseline as it was not included in the original protocol, and 2 participants were unable to perform the test due to underlying medical issues.

Change From Baseline Over Time in Sit-to-Stand (STS) Test

Left arm lifts in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W, titrated up to a maximum of 2.0 mg/kg Q2W.

Left Upper Extremity

Right arm lifts in participants who received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously Q4W, titrated up to a maximum of 2.0 mg/kg Q2W.

Right Upper Extremity

TIO analysis set with available WAL measurements at Baseline and each time point.

Change From Baseline Over Time in Weighted Arm Lift (WAL) Test

TIO analysis set with available 6MWT measurements at Baseline and each time point. Six participants did not perform the test at Baseline as it was not included in the original protocol, and 2 participants were unable to perform the test due to underlying medical issues.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Burosumab (KRN23) in Adults With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)	NCT02304367	Tumor Induced O... Epidermal Nevus...	Burosumab	18 Years -	Kyowa Kirin Co., Ltd.
Study of Burosumab (KRN23) in Adults With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)	NCT02304367	Tumor Induced O... Epidermal Nevus...	Burosumab	18 Years -	Kyowa Kirin Co., Ltd.
Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations	NCT01752920	Solid Tumor	Derazantinib lo... Derazantinib mi... Derazantinib hi... Derazantinib at...	18 Years -	Basilea Pharmaceutica

Spots Global Cancer Trial Database for fgf23

Every month we try and update this database with for fgf23 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for fgf23

Every month we try and update this database with for fgf23 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for fgf23 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.