Oncogenic Osteomalacia, Tumor-Induced Osteomalacia
Conditions
Keywords
FGF-23, Fibroblast Growth Factor (FGF23), Hypophosphatemia
Brief summary
Background: People with tumor-induced osteomalacia (TIO) have small tumors that may cause low blood phosphorus, weak muscles, bone pain, and broken bones. The tumors may be so small they are hard to find or impossible to remove. Researchers want to test a drug that may help treat TIO. Objective: To see how the drug BGJ398 affects people with tumor-induced osteomalacia. Eligibility: People ages 18-85 who are in NIH protocol 01-D-0184 and have TIO that cannot be found or easily removed Design: At every study visit, participants will have: * Medical history * Physical exam * Blood and urine tests * Questions about their health and fatigue At the screening visit, participants will also have a heart and eye tests. They may have other tests to find their tumor. The baseline visit will be a 1-week stay in the clinic. Participants will have the regular study tests, plus: * Their first dose of the study drug capsules * Blood and urine collected every 2-4 hours for 24 hours. A thin plastic tube will be inserted in a vein to collect blood. * Heart and kidney ultrasounds * Activities that test strength * 6-minute walk test Participants will take the study drug for six 1-month cycles. In each cycle, participants will: * Take the study drug every day for 4 weeks. * Have 1 visit. Participants will collect their urine for 24 hours and have their blood drawn. Participants will have the regular study tests and repeat some baseline tests. * Have blood and urine tests at their local lab. Participants will have 1 visit at the end of the last cycle and another 3 months later....
Detailed description
Background: * Tumor-induced osteomalacia (TIO) is a rare disorder in which fibroblast growth factor (FGF23)-producing neoplasms cause renal phosphate wasting and skeletal disease. * Recent studies have shown that chromosomal translocations causing a fibronectin-FGFR1 (FN1/FGFR1) fusion gene have been identified in 40-60% of these tumors. * BGJ398 is an orally bio-available, selective and ATP competitive pan-fibroblast growth factor receptor (FGFR) kinase inhibitor which has demonstrated anti-tumor activity in preclinical, in vitro and in-vivo tumor models harboring FGFR genetic alterations. Objectives: To induce complete metabolic response in subjects with tumor-induced osteomalacia (TIO) with BGJ-398 as demonstrated by normalization of FGF23 and phosphate homeostasis. Eligibility: Patients may be eligible if they: * Are adults 18-85 years with documented evidence of TIO due to a non-localized or unresectable tumor, or metastatic disease, or resectable tumor that cannot be easily removed. * Are not taking any exclusionary medications or foods that may interfere with BGJ398. * Are not pregnant or nursing and are willing to use contraception (at least two forms of contraception), if able to become pregnant. * Have no significant ophthalmologic, gastrointestinal, renal, or hematologic disease. Design: * Phase 2, open-label, non-randomized, single-arm, drug treatment trial. * 10 subjects to be studied. * Treatment duration 6 months with 3 months off drug follow-up and optional extension phase. * Monthly NIH visits with additional labs obtained in between visits. * Imaging performed in those with identifiable tumors. * Analyses to include repeated measures ANOVA assessing changes in biochemical indices over time in response to BGJ398.
Interventions
DRUGBGJ398
BGJ398, a pan-fibroblast growth factor receptor (FGFR) kinase inhibitor will be orally administered over six 4-week cycles (4 weeks on drug continuously). After the initial dose, escalation/de- escalation of BGJ398 will be based on FGF- 23 blood levels and adjusted according to protocol procedures. The six cycles of BGJ398 will be followed by 3 months off the drug and an optional extension phase.
Sponsors
National Institute of Dental and Craniofacial Research (NIDCR)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Patients eligible for inclusion in this study have to meet all of the following criteria: * Aged 18-85 years * Diagnosis of TIO due to a non-localized or unresectable tumor, or metastatic disease or resectable tumor that cannot be removed by minor surgical procedure. This diagnosis will be confirmed prior to enrollment on protocol 01-D-0184. Where clinically indicated, genetic testing to rule-out heritable causes of FGF23 excess will also be performed on 01-D-0184. * Willing and able to comply with scheduled visits, treatment plan and laboratory tests. * Able to swallow and retain oral medication. * Able to provide informed consent
Exclusion criteria
Patients eligible for this study must not meet any of the following criteria: * Have another genetic or secondary cause of hypophosphatemia. * History of any other malignancy that has not been cured/in remission for 5 years. * Patients who previously received treatment with an FGFR inhibitor other than BGJ398. * Current evidence of corneal or retinal disorder/keratopathy including, but not limited to: bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjuctivitis, confirmed by ophthalmologic examination * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BGJ398 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) * Patients who are currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 are prohibited. This includes treatment with enzyme-inducing antiepileptic drugs including carbamazepine, phenytoin, phenobarbital, and primidone. * Consumption of grapefruit, grapefruit juice, pomegranates, star fruits, Seville oranges or products within 7 days prior to first dose * Use of amiodarone within 90 days prior to first dose * Current use of therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulants. Heparin and/or low molecular weight heparins are allowed. * Insufficient bone marrow function defined as all of the following: * ANC \<1,500/mm\^3 \[1.0 x 10\^9/L\] AND * Platelets \< 75,000/mm\^3 \[75 x 10\^9/L\] AND * Hemoglobin \< 10.0 g/dL * Insufficient hepatic and renal function defined as one of the following: * Total bilirubin \> 1.5x ULN OR * AST/SGOT and ALT/SGPT \> 2x ULN OR * Blood creatinine \> 1.5xULN and/or calculated eGFR \< 45 ml/min/1.73 m\^2 (calculated by CKD-Epi) * Clinically significant cardiac disease including any of the following: * Congestive heart failure requiring treatment (NY Heart Association grade \>= 2), * History or presence of clinically significant ventricular arrhythmias, atrial fibrillation, resting bradycardia, or conduction abnormality * Unstable angina pectoris or acute myocardial infarction less than or equal to 3 months prior to starting study drug * QTcF \> 450 msec (males); \> 470 msec (females) * History of congenital long QT syndrome * Recent (less than or equal to 3 months) transient ischemic attack or stroke * Patients under age 21 will have a bone age assessed as part of their clinically indicated skeletal survey under 01-D-0184 and will not be offered enrollment if their growth plates are open. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment * Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject. * Combination of the following (a+b or a+c, or b+c): * Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception * Placement of an intrauterine device (IUD) or intrauterine system (IUS) * Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository * Post-menopausal women are allowed to participate in this study. Women are considered post- menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH \>40 mIU/ml or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. * Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of the study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. * Patients with TIO who are currently taking BGJ398 or have been treated with BGJ398 in the past are eligible to participate in this study, provided that they discontinue BGJ398 for 2 weeks prior to the baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Metabolic Remission After Stopping BGJ398 | Up to 12 weeks after stopping BGJ398 | Participants were monitored for up to 12 weeks after stopping BGJ398. A participant was considered to have a complete metabolic remission by achieving both normal blood FGF23 and phosphorus levels in the blood for 12 weeks after stopping BGJ398. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events | 24 week treatment phase followed by 3 month follow up or extension phase | Percentage of patients who incurred grade 3 or 4 adverse events (AEs) or serious adverse events (SAE) or AEs causing dose interruption/reduction |
| Six-Minute Walk Test | Assessed at baseline and 24 weeks after starting BGJ398 | The Six-Minute Walk Test (6MWT), is a self-paced practical test that measures the distance the patient can quickly cover on a flat, hard surface. Each subject was instructed to complete the maximum distance possible in six minutes. Feedback was given in two minute intervals and during the last 30 seconds. Patients were instructed to notify test administrator of leg cramping, pain, nausea, dizziness and shortness of breath. Test administrators counted each lap and upon test completion, the partial distance is measured and added to where the subject stopped. |
| Hand Grip Strength Test | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | The person is seated, lower extremities flexed at 90 degrees. The individual uses the dominant hand for this activity. The individual sit with shoulder adducted and neutrally rotated elbow flexed at 90 degrees, forearm in neutral position, resting on the arm of a chair. The JAMAR Hand Dynamometer set to the third level position from the inside is used. The examiner lightly supports the readout dial to prevent it from dropping. The patient is asked to Squeeze as hard as you can….squeeze…..squeeze….relax. Three successive trials is recorded in kilograms. A 10-15 second break occurs to prevent muscle fatigue. Scores are recorded and averaged for the final result. Scores within two standard deviations of the mean are considered within normal limits. |
| Pinch Test | Assessed at baseline and every 4 weeks for the 24 treatment period, and every 4 weeks in the follow up phase, up to 37 weeks | A lateral pinch is required of the patient, using the dominant hand. The individual is seated, lower extremities flexed at 90 degrees. The examiner stabilizes the patient's wrist as the patient holds the pinch gauge to perform the test. The examiner requests the person to pinch with maximum strength. The peak-hold needle will automatically record the highest force exerted. After the patient uses the Pinch gauge, the examiner records the reading and resets the peak-hold needle to zero before testing again. Three lateral pinch trials are recorded and averaged for the final result. |
| Five Times Sit-to-Stand Test | Assessed at baseline and every 4 weeks during the 24 week treatment period | The Five Times Sit to Stand Test measures an aspect of transfer skill. The test provides a method to quantify functional lower extremity strength and/or identify movement strategies a patient uses to complete transitional movements. The chair is free standing. Patient sits with arms folded across chest and with their back against the chair. A standard chair height 44 cm was used for each patient. Patient stands fully between repetitions of the test, careful to not touch the back of the chair during each repetition. Patient instructions: I want you to stand up and sit down 5 times as quickly as you can when I say Go. Timing begins at Go and ends when the buttocks touches the chair after the 5th repetition. The results are recorded in seconds. |
| The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) The minimum score value is 0, maximum is 100, where a higher school represents a worse outcome (significant symptoms/disability) |
| RAND SF-36 Survey Results | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | Evaluation using the RAND 36-Item Short Form Survey (SF-36). Results were separated into 8 domains - Physical Functioning, Role limitations due to physical health problems, Role limitations due to emotional problems, Emotional well-being, Energy/fatigue, Social functioning, Bodily Pain, and General health perceptions. The minimum value is 0, the maximum value is 100, which the higher the score, the better the outcome. |
| PROMIS Fatigue | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased feelings of fatigue. |
| PROMIS Pain Interference Score | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Pain Interference 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased pain interference |
| Number of Participants With Complete and Partial Metabolic Response Rate | Every 2 weeks up to 24 weeks | Participants were monitored for metabolic response to BGJ398 every other week. A participant was considered to have a complete metabolic response by achieving both normal c-terminal FGF23 and phosphorus levels at each time point. A participant was considered to have a partial metabolic response by achieving both a decrease of at least 50% in c-terminal FGF23 levels and an increase of at least 50% in phosphorous at each time point |
| Blood Intact FGF23 Levels | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | Measured Blood Intact FGF23 Levels. |
| Blood C-terminal FGF23 Level | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | — |
| Blood Phosphate Levels | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | — |
| Blood 1,25-(OH)2-Vitamin D Level | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | — |
| Blood Alkaline Phosphatase | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | — |
| Tubular Reabsorption of Phosphate | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | Tubular Reabsorption of Phosphate was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples. |
| Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | Tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples. |
| Radiographic Evidence of Tumor-Induced Osteomalacia | Baseline and at 24 weeks | In patients with radiographic evidence of TIO, 18FDG PET scans were performed |
| PROMIS Mobility Score | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Mobility bank. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents a better outcome (unencumbered mobility) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm (TIO Subjects) Phase 2, open-label, non-randomized, single-arm, drug treatment trial. 10 subjects will be studied. Treatment duration of 6 months with 3 months off drug follow-up and optional extension phase.
BGJ398: BGJ398, a pan-fibroblast growth factor receptor (FGFR) kinase inhibitor will be orally administered over six 4-week cycles (3 weeks on drug, 1 week off drug). After the initial dose, escalation/de- escalation of BGJ398 will be based on FGF- 23 blood levels and adjusted according to protocol procedures. The six cycles of BGJ398 will be followed by 3 months off the drug and an optional extension phase. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Single Arm (TIO Subjects) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 33.75 years STANDARD_DEVIATION 7.8 |
| Blood Alkaline Phosphatase on Initiation of Study | 134 U/L STANDARD_DEVIATION 54 |
| Blood C-Terminal FGF23 on Initiation of Study | 814 RU/mL STANDARD_DEVIATION 911 |
| Blood Intact FGF23 on Initiation of Sutdy | 1384 pg/mL STANDARD_DEVIATION 1467 |
| Blood Phosphate on Initiation of Study | 1.6 mg/dL STANDARD_DEVIATION 0.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
| Type of TIO Disease Localized | 2 Participants |
| Type of TIO Disease Metastatic | 0 Participants |
| Type of TIO Disease Non-localized | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Number of Participants With Complete Metabolic Remission After Stopping BGJ398
Participants were monitored for up to 12 weeks after stopping BGJ398. A participant was considered to have a complete metabolic remission by achieving both normal blood FGF23 and phosphorus levels in the blood for 12 weeks after stopping BGJ398.
Time frame: Up to 12 weeks after stopping BGJ398
Population: The population consisted of all participants enrolled in the study
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete Metabolic Remission After Stopping BGJ398 | Complete Metabolic Remission | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete Metabolic Remission After Stopping BGJ398 | No Complete Metabolic Remission | 4 Participants |
Secondary
Blood 1,25-(OH)2-Vitamin D Level
Time frame: Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Baseline | 22.5 pg/mL | Standard Deviation 16.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 2 | 112.3 pg/mL | Standard Deviation 94.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 4 | 79 pg/mL | Standard Deviation 68.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 6 | 202.8 pg/mL | Standard Deviation 246.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 8 | 64.7 pg/mL | Standard Deviation 30.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 10 | 85.7 pg/mL | Standard Deviation 63.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 12 | 96.5 pg/mL | Standard Deviation 61.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 14 | 59.8 pg/mL | Standard Deviation 28.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 16 | 36 pg/mL | Standard Deviation 6.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 18 | 86.5 pg/mL | Standard Deviation 56.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 20 | 33 pg/mL | Standard Deviation 12.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 22 | 22.5 pg/mL | Standard Deviation 19.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Week 24 | 80.3 pg/mL | Standard Deviation 35.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood 1,25-(OH)2-Vitamin D Level | Follow up | 51 pg/mL | Standard Deviation 32.2 |
Secondary
Blood Alkaline Phosphatase
Time frame: Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Baseline | 132 IU/L | Standard Deviation 52.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 2 | 178.8 IU/L | Standard Deviation 50.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 4 | 186.5 IU/L | Standard Deviation 42.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 6 | 198 IU/L | Standard Deviation 36.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 8 | 171.8 IU/L | Standard Deviation 26.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 10 | 181.3 IU/L | Standard Deviation 22 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 12 | 170 IU/L | Standard Deviation 18.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 14 | 188.3 IU/L | Standard Deviation 29.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 16 | 175.5 IU/L | Standard Deviation 14.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 18 | 183 IU/L | Standard Deviation 40.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 20 | 190.3 IU/L | Standard Deviation 33.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 22 | 200.7 IU/L | Standard Deviation 48 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Week 24 | 192.3 IU/L | Standard Deviation 67.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Alkaline Phosphatase | Follow up | 185.7 IU/L | Standard Deviation 17 |
Secondary
Blood C-terminal FGF23 Level
Time frame: Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | Baseline | 814 RU/mL | Standard Deviation 911 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 2 Weeks | 213 RU/mL | Standard Deviation 158 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 4 Weeks | 330 RU/mL | Standard Deviation 87 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 6 Weeks | 229 RU/mL | Standard Deviation 123 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 8 Weeks | 304 RU/mL | Standard Deviation 154 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 10 Weeks | 2225 RU/mL | Standard Deviation 2015 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 12 Weeks | 430 RU/mL | Standard Deviation 409 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 14 Weeks | 270 RU/mL | Standard Deviation 65 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 16 Weeks | 360 RU/mL | Standard Deviation 75 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 18 Weeks | 185 RU/mL | Standard Deviation 151 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 20 Weeks | 274 RU/mL | Standard Deviation 118 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 22 Weeks | 368 RU/mL | Standard Deviation 272 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | 24 Weeks | 463 RU/mL | Standard Deviation 102 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood C-terminal FGF23 Level | Follow up | 1568 RU/mL | Standard Deviation 1863 |
Secondary
Blood Intact FGF23 Levels
Measured Blood Intact FGF23 Levels.
Time frame: Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | Baseline | 1384 pg/mL | Standard Deviation 1467 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | 4 Weeks | 282 pg/mL | Standard Deviation 254 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | 8 Weeks | 286 pg/mL | Standard Deviation 236 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | 12 Weeks | 596 pg/mL | Standard Deviation 924 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | 16 Weeks | 310 pg/mL | Standard Deviation 202 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | 20 Weeks | 135 pg/mL | Standard Deviation 67 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | 24 Weeks | 439 pg/mL | Standard Deviation 230 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Intact FGF23 Levels | Follow up | 2534.8 pg/mL | Standard Deviation 2824.6 |
Secondary
Blood Phosphate Levels
Time frame: Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 10 | 3.1 mg/dL | Standard Deviation 0.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Baseline | 1.6 mg/dL | Standard Deviation 0.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 2 | 2.7 mg/dL | Standard Deviation 0.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 4 | 2.9 mg/dL | Standard Deviation 1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 6 | 3.2 mg/dL | Standard Deviation 1.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 8 | 3.6 mg/dL | Standard Deviation 1.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 12 | 2.9 mg/dL | Standard Deviation 1.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 14 | 2.8 mg/dL | Standard Deviation 1.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 16 | 3.4 mg/dL | Standard Deviation 1.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 18 | 2.5 mg/dL | Standard Deviation 0.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 20 | 3.0 mg/dL | Standard Deviation 1.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 22 | 3.3 mg/dL | Standard Deviation 2.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Week 24 | 3.0 mg/dL | Standard Deviation 1.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Blood Phosphate Levels | Follow up | 2.3 mg/dL | Standard Deviation 0.4 |
Secondary
Five Times Sit-to-Stand Test
The Five Times Sit to Stand Test measures an aspect of transfer skill. The test provides a method to quantify functional lower extremity strength and/or identify movement strategies a patient uses to complete transitional movements. The chair is free standing. Patient sits with arms folded across chest and with their back against the chair. A standard chair height 44 cm was used for each patient. Patient stands fully between repetitions of the test, careful to not touch the back of the chair during each repetition. Patient instructions: I want you to stand up and sit down 5 times as quickly as you can when I say Go. Timing begins at Go and ends when the buttocks touches the chair after the 5th repetition. The results are recorded in seconds.
Time frame: Assessed at baseline and every 4 weeks during the 24 week treatment period
Population: Only 2 patients performed strength testing at 28 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Baseline | 14.7 seconds | Standard Deviation 6.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Week 4 | 13.2 seconds | Standard Deviation 4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Week 8 | 13.5 seconds | Standard Deviation 1.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Week 12 | 11.2 seconds | Standard Deviation 0.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Week 16 | 10.5 seconds | Standard Deviation 1.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Week 20 | 10.8 seconds | Standard Deviation 0.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Week 24 | 11.1 seconds | Standard Deviation 0.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Five Times Sit-to-Stand Test | Week 28 | 11.1 seconds | Standard Deviation 1 |
Secondary
Hand Grip Strength Test
The person is seated, lower extremities flexed at 90 degrees. The individual uses the dominant hand for this activity. The individual sit with shoulder adducted and neutrally rotated elbow flexed at 90 degrees, forearm in neutral position, resting on the arm of a chair. The JAMAR Hand Dynamometer set to the third level position from the inside is used. The examiner lightly supports the readout dial to prevent it from dropping. The patient is asked to Squeeze as hard as you can….squeeze…..squeeze….relax. Three successive trials is recorded in kilograms. A 10-15 second break occurs to prevent muscle fatigue. Scores are recorded and averaged for the final result. Scores within two standard deviations of the mean are considered within normal limits.
Time frame: Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: Only 2 patients performed strength testing at 28 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Baseline | 14.7 kg | Standard Deviation 11.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Week 4 | 16.4 kg | Standard Deviation 11.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Week 8 | 18.5 kg | Standard Deviation 9.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Week 12 | 17.0 kg | Standard Deviation 7.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Week 16 | 22.6 kg | Standard Deviation 18.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Week 20 | 17.3 kg | Standard Deviation 6.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Week 24 | 15.5 kg | Standard Deviation 1.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Hand Grip Strength Test | Week 28 | 30.1 kg | Standard Deviation 6.7 |
Secondary
Number of Participants With Complete and Partial Metabolic Response Rate
Participants were monitored for metabolic response to BGJ398 every other week. A participant was considered to have a complete metabolic response by achieving both normal c-terminal FGF23 and phosphorus levels at each time point. A participant was considered to have a partial metabolic response by achieving both a decrease of at least 50% in c-terminal FGF23 levels and an increase of at least 50% in phosphorous at each time point
Time frame: Every 2 weeks up to 24 weeks
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Baseline | Complete Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Baseline | Partial Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Baseline | Neither Complete or Partial Metabolic Response | 4 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 2 | Complete Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 2 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 2 | Neither Complete or Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 4 | Complete Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 4 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 4 | Neither Complete or Partial Metabolic Response | 3 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 6 | Complete Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 6 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 6 | Neither Complete or Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 8 | Complete Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 8 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 8 | Neither Complete or Partial Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 10 | Complete Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 10 | Partial Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 10 | Neither Complete or Partial Metabolic Response | 4 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 12 | Complete Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 12 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 12 | Neither Complete or Partial Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 14 | Complete Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 14 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 14 | Neither Complete or Partial Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 16 | Complete Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 16 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 16 | Neither Complete or Partial Metabolic Response | 3 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 18 | Complete Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 18 | Partial Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 18 | Neither Complete or Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 20 | Complete Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 20 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 20 | Neither Complete or Partial Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 22 | Complete Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 22 | Partial Metabolic Response | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 22 | Neither Complete or Partial Metabolic Response | 2 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 24 - prior to drug discontinuation | Complete Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 24 - prior to drug discontinuation | Partial Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 24 - prior to drug discontinuation | Neither Complete or Partial Metabolic Response | 4 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 24 - after drug discontinuation | Complete Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 24 - after drug discontinuation | Partial Metabolic Response | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Complete and Partial Metabolic Response Rate | Week 24 - after drug discontinuation | Neither Complete or Partial Metabolic Response | 4 Participants |
Secondary
Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events
Percentage of patients who incurred grade 3 or 4 adverse events (AEs) or serious adverse events (SAE) or AEs causing dose interruption/reduction
Time frame: 24 week treatment phase followed by 3 month follow up or extension phase
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events | SAE | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events | Grade 4 AE | 0 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events | Grade 3 AE | 1 Participants |
| TIO Subjects Who Received BGJ398 (Single Arm) | Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events | AE leading to dose interruption/reduction | 4 Participants |
Secondary
Pinch Test
A lateral pinch is required of the patient, using the dominant hand. The individual is seated, lower extremities flexed at 90 degrees. The examiner stabilizes the patient's wrist as the patient holds the pinch gauge to perform the test. The examiner requests the person to pinch with maximum strength. The peak-hold needle will automatically record the highest force exerted. After the patient uses the Pinch gauge, the examiner records the reading and resets the peak-hold needle to zero before testing again. Three lateral pinch trials are recorded and averaged for the final result.
Time frame: Assessed at baseline and every 4 weeks for the 24 treatment period, and every 4 weeks in the follow up phase, up to 37 weeks
Population: Only 2 patients performed strength testing at 28 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Baseline | 6.8 kg | Standard Deviation 4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Week 4 | 6.7 kg | Standard Deviation 1.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Week 8 | 6.8 kg | Standard Deviation 1.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Week 12 | 7.5 kg | Standard Deviation 2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Week 16 | 7.5 kg | Standard Deviation 1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Week 20 | 7.7 kg | Standard Deviation 1.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Week 24 | 7.0 kg | Standard Deviation 1.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Pinch Test | Week 28 | 8.1 kg | Standard Deviation 1.9 |
Secondary
PROMIS Fatigue
Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased feelings of fatigue.
Time frame: Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Baseline | 55.1 T score | Standard Deviation 8.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Week 4 | 47.4 T score | Standard Deviation 1.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Week 8 | 52.6 T score | Standard Deviation 7.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Week 12 | 52.3 T score | Standard Deviation 9.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Week 16 | 52.3 T score | Standard Deviation 9.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Week 20 | 46.6 T score | Standard Deviation 9.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Week 24 | 52 T score | Standard Deviation 4.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Fatigue | Week 28 | 46.7 T score | Standard Deviation 8.1 |
Secondary
PROMIS Mobility Score
Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Mobility bank. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents a better outcome (unencumbered mobility)
Time frame: Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: Only 2 patients completed the week 28 surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Baseline | 38.2 T score | Standard Deviation 6.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Week 4 | 40.0 T score | Standard Deviation 6.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Week 8 | 39.3 T score | Standard Deviation 5.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Week 12 | 38.8 T score | Standard Deviation 3.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Week 16 | 40.2 T score | Standard Deviation 4.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Week 20 | 40.7 T score | Standard Deviation 7.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Week 24 | 39.5 T score | Standard Deviation 2.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Mobility Score | Week 28 | 43.6 T score | Standard Deviation 1.6 |
Secondary
PROMIS Pain Interference Score
Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Pain Interference 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased pain interference
Time frame: Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: Only 2 patients completed the week 28 surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Week 20 | 48.2 T score | Standard Deviation 15 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Week 16 | 49.0 T score | Standard Deviation 10.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Baseline | 56.4 T score | Standard Deviation 4.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Week 4 | 52.6 T score | Standard Deviation 9.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Week 8 | 52.5 T score | Standard Deviation 6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Week 12 | 55.7 T score | Standard Deviation 4.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Week 24 | 52.6 T score | Standard Deviation 9.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | PROMIS Pain Interference Score | Week 28 | 40.7 T score | Standard Deviation 0 |
Secondary
Radiographic Evidence of Tumor-Induced Osteomalacia
In patients with radiographic evidence of TIO, 18FDG PET scans were performed
Time frame: Baseline and at 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Radiographic Evidence of Tumor-Induced Osteomalacia | Baseline SUVmax Tumor | 7.9 Units | Standard Deviation 1.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Radiographic Evidence of Tumor-Induced Osteomalacia | 24 Week SUVmax tumor | 3.9 Units | Standard Deviation 1.3 |
Secondary
RAND SF-36 Survey Results
Evaluation using the RAND 36-Item Short Form Survey (SF-36). Results were separated into 8 domains - Physical Functioning, Role limitations due to physical health problems, Role limitations due to emotional problems, Emotional well-being, Energy/fatigue, Social functioning, Bodily Pain, and General health perceptions. The minimum value is 0, the maximum value is 100, which the higher the score, the better the outcome.
Time frame: Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: Only 2 patients completed week 28 surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - Baseline | 46.3 score on a scale | Standard Deviation 18.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - 4 weeks | 47.5 score on a scale | Standard Deviation 21 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - 8 weeks | 51.3 score on a scale | Standard Deviation 16.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - 12 weeks | 47.5 score on a scale | Standard Deviation 12.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - 16 weeks | 56.0 score on a scale | Standard Deviation 16.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - 20 weeks | 52.5 score on a scale | Standard Deviation 26 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - 24 weeks | 41.0 score on a scale | Standard Deviation 6.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Physical Functioning - 28 weeks | 65.0 score on a scale | Standard Deviation 7.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - Baseline | 43.8 score on a scale | Standard Deviation 12.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - 4 weeks | 93.8 score on a scale | Standard Deviation 12.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - 8 weeks | 68.8 score on a scale | Standard Deviation 31.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - 12 weeks | 50 score on a scale | Standard Deviation 35.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - 16 weeks | 50 score on a scale | Standard Deviation 57.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - 20 weeks | 75 score on a scale | Standard Deviation 50 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - 24 weeks | 25 score on a scale | Standard Deviation 50 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to physical health problems - 28 weeks | 12.5 score on a scale | Standard Deviation 17.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - Baseline | 66.7 score on a scale | Standard Deviation 27.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - 4 weeks | 83.3 score on a scale | Standard Deviation 33.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - 8 weeks | 75 score on a scale | Standard Deviation 31.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - 12 weeks | 66.7 score on a scale | Standard Deviation 47.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - 16 weeks | 50 score on a scale | Standard Deviation 43 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - 20 weeks | 91.7 score on a scale | Standard Deviation 16.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - 24 weeks | 41.7 score on a scale | Standard Deviation 50 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Role limitations due to emotional problems - 28 weeks | 33.3 score on a scale | Standard Deviation 47.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - Baseline | 67 score on a scale | Standard Deviation 15.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - 4 weeks | 72 score on a scale | Standard Deviation 15.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - 8 weeks | 72 score on a scale | Standard Deviation 12.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - 12 weeks | 72 score on a scale | Standard Deviation 17.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - 16 weeks | 69.8 score on a scale | Standard Deviation 21.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - 20 weeks | 73 score on a scale | Standard Deviation 8.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - 24 weeks | 62 score on a scale | Standard Deviation 10.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Emotional well-being - 28 weeks | 72 score on a scale | Standard Deviation 5.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - Baseline | 50 score on a scale | Standard Deviation 29.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - Week 4 | 58.8 score on a scale | Standard Deviation 8.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - week 8 | 52.5 score on a scale | Standard Deviation 22.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - week 12 | 46.3 score on a scale | Standard Deviation 28.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - week 16 | 61.3 score on a scale | Standard Deviation 31.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - week 20 | 57.5 score on a scale | Standard Deviation 18.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - week 24 | 48.8 score on a scale | Standard Deviation 33.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Energy/fatigue - week 28 | 47.5 score on a scale | Standard Deviation 53 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - Baseline | 59.4 score on a scale | Standard Deviation 37.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - 4 weeks | 87.5 score on a scale | Standard Deviation 14.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - 8 weeks | 78.1 score on a scale | Standard Deviation 21.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - 12 weeks | 81.3 score on a scale | Standard Deviation 16.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - 16 weeks | 75 score on a scale | Standard Deviation 27 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - 20 weeks | 78.1 score on a scale | Standard Deviation 25.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - 24 weeks | 71.9 score on a scale | Standard Deviation 32.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Social functioning - 28 weeks | 75 score on a scale | Standard Deviation 17.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - Baseline | 51.9 score on a scale | Standard Deviation 29.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - week 4 | 66.3 score on a scale | Standard Deviation 28 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - week 8 | 63.1 score on a scale | Standard Deviation 37.4 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - week 12 | 43.1 score on a scale | Standard Deviation 26.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - week 16 | 72.5 score on a scale | Standard Deviation 34.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - week 20 | 75 score on a scale | Standard Deviation 20.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - week 24 | 36.2 score on a scale | Standard Deviation 2.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | Bodily Pain - week 28 | 90 score on a scale | Standard Deviation 0 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - Baseline | 60 score on a scale | Standard Deviation 10.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - week 4 | 68.8 score on a scale | Standard Deviation 13.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - week 8 | 72.5 score on a scale | Standard Deviation 16.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - week 12 | 73.8 score on a scale | Standard Deviation 25.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - week 16 | 71.3 score on a scale | Standard Deviation 14.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - week 20 | 67.5 score on a scale | Standard Deviation 23.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - week 24 | 71.3 score on a scale | Standard Deviation 18 |
| TIO Subjects Who Received BGJ398 (Single Arm) | RAND SF-36 Survey Results | General health perceptions - week 28 | 67.5 score on a scale | Standard Deviation 31.8 |
Secondary
Six-Minute Walk Test
The Six-Minute Walk Test (6MWT), is a self-paced practical test that measures the distance the patient can quickly cover on a flat, hard surface. Each subject was instructed to complete the maximum distance possible in six minutes. Feedback was given in two minute intervals and during the last 30 seconds. Patients were instructed to notify test administrator of leg cramping, pain, nausea, dizziness and shortness of breath. Test administrators counted each lap and upon test completion, the partial distance is measured and added to where the subject stopped.
Time frame: Assessed at baseline and 24 weeks after starting BGJ398
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Six-Minute Walk Test | Baseline | 320.4 Meters | Standard Deviation 221.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Six-Minute Walk Test | 24 Weeks | 496 Meters | Standard Deviation 173.4 |
Secondary
The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH)
The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) The minimum score value is 0, maximum is 100, where a higher school represents a worse outcome (significant symptoms/disability)
Time frame: Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: 2 patients did not fill out their DASH at week 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Baseline | 16.5 DASH Disability/Symptom Score | Standard Deviation 4.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Week 4 | 13.3 DASH Disability/Symptom Score | Standard Deviation 6.8 |
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Week 8 | 14.2 DASH Disability/Symptom Score | Standard Deviation 4.6 |
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Week 12 | 13.3 DASH Disability/Symptom Score | Standard Deviation 7.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Week 16 | 12.7 DASH Disability/Symptom Score | Standard Deviation 6.7 |
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Week 20 | 21.0 DASH Disability/Symptom Score | Standard Deviation 23.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Week 24 | 12.1 DASH Disability/Symptom Score | Standard Deviation 8.1 |
| TIO Subjects Who Received BGJ398 (Single Arm) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | Week 28 | 10.0 DASH Disability/Symptom Score | Standard Deviation 2.3 |
Secondary
Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)
Tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples.
Time frame: Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Missing urine samples resulted in several time points having fewer than 4 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Baseline | 1.1 mg/dL | Standard Deviation 0.5 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 2 | 2.5 mg/dL | Standard Deviation 1.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 4 | 2.3 mg/dL | Standard Deviation 1.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 6 | 3.5 mg/dL | Standard Deviation 2.2 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 8 | 3.4 mg/dL | Standard Deviation 2.3 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 10 | 1.32 mg/dL | Standard Deviation 0.9 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 12 | 1.52 mg/dL | Standard Deviation 1.86 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 14 | 2.76 mg/dL | Standard Deviation 1.61 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 16 | 3.44 mg/dL | Standard Deviation 2.47 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 18 | 1.98 mg/dL | Standard Deviation 0.34 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 20 | 2.31 mg/dL | Standard Deviation 1.25 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 22 | 3.86 mg/dL | Standard Deviation 2.99 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Week 24 | 2.61 mg/dL | Standard Deviation 1.87 |
Secondary
Tubular Reabsorption of Phosphate
Tubular Reabsorption of Phosphate was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples.
Time frame: Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks
Population: There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Missing urine samples resulted in several time points having fewer than 4 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 8 | 78 % Filtered Phosphate | Standard Deviation 19 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Baseline | 67 % Filtered Phosphate | Standard Deviation 20 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 2 | 82 % Filtered Phosphate | Standard Deviation 13 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 4 | 79 % Filtered Phosphate | Standard Deviation 14 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 6 | 84 % Filtered Phosphate | Standard Deviation 14 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 10 | 50 % Filtered Phosphate | Standard Deviation 36 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 12 | 45 % Filtered Phosphate | Standard Deviation 36 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 14 | 82 % Filtered Phosphate | Standard Deviation 15 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 16 | 81 % Filtered Phosphate | Standard Deviation 15 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 18 | 77 % Filtered Phosphate | Standard Deviation 13 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 20 | 75 % Filtered Phosphate | Standard Deviation 12 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 22 | 81 % Filtered Phosphate | Standard Deviation 11 |
| TIO Subjects Who Received BGJ398 (Single Arm) | Tubular Reabsorption of Phosphate | Week 24 | 74 % Filtered Phosphate | Standard Deviation 19 |