BGJ398 for the Treatment of Tumor-Induced Osteomalacia

• Sponsor: National Institute of Dental and Craniofacial Research (NIDCR) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT03510455
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Actual Duration (Months): 14.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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....

Condition or Disease	Intervention/Treatment	Phase
Tumor-Induced Osteomalacia; Oncogenic Osteomalacia	Drug: BGJ398	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BGJ398 for the Treatment of Tumor-Induced Osteomalacia
• Actual Study Start Date: Feb 27, 2019
• Actual Primary Completion Date: Feb 28, 2020
• Actual Study Completion Date: May 4, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: BGJ398; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. 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.

4. 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.

5. 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.

6. 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.

7. 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)

8. 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.

9. 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.

10. 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

11. 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)

12. 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.

13. 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]

14. 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]

15. 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]

16. 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]

17. 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.

18. 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.

19. Radiographic Evidence of Tumor-Induced Osteomalacia [Baseline and at 24 weeks]

    In patients with radiographic evidence of TIO, 18FDG PET scans were performed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR)

Investigators

• Principal Investigator: Rachel I Gafni, M.D., National Institute of Dental and Craniofacial Research (NIDCR)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 21, 2019

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: National Institute of Dental and Craniofacial Research (NIDCR)
• ClinicalTrials.gov Identifier: NCT03510455
• Other Study ID Numbers: 180086; 18-D-0086
• First Posted: Apr 27, 2018
• Last Update Posted: Apr 8, 2021
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Dental and Craniofacial Research (NIDCR): FGF-23; Fibroblast Growth Factor (FGF23); Hypophosphatemia
• Additional relevant MeSH terms: Neoplasms, Connective Tissue; Osteomalacia; Infigratinib

Study Results

Participant Flow

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Period Title: Overall Study
STARTED	4
Treated	4
Extension Phase	1
Screening Failures	0
COMPLETED	3
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Single Arm (TIO Subjects)
Arm/Group Description	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.
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.75 (7.8)
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	4 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 50%
White	2 50%
More than one race	0 0%
Unknown or Not Reported	0 0%
Type of TIO Disease (Count of Participants)
Localized	2 50%
Non-localized	2 50%
Metastatic	0 0%
Blood Intact FGF23 on Initiation of Sutdy (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	1384 (1467)
Blood C-Terminal FGF23 on Initiation of Study (RU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [RU/mL]	814 (911)
Blood Phosphate on Initiation of Study (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.6 (0.3)
Blood Alkaline Phosphatase on Initiation of Study (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	134 (54)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Metabolic Remission After Stopping BGJ398
Description	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

Outcome Measure Data

Analysis Population Description

The population consisted of all participants enrolled in the study

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Complete Metabolic Remission	0 0%
No Complete Metabolic Remission	4 100%

2. Secondary Outcome

Title	Number of Participants With Complete and Partial Metabolic Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm (TIO Subjects)
Arm/Group Description	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 (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.
Measure Participants	4
Complete Metabolic Response	0 0%
Partial Metabolic Response	0 0%
Neither Complete or Partial Metabolic Response	4 100%
Complete Metabolic Response	2 50%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	1 25%
Complete Metabolic Response	0 0%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	3 75%
Complete Metabolic Response	2 50%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	1 25%
Complete Metabolic Response	1 25%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	2 50%
Complete Metabolic Response	0 0%
Partial Metabolic Response	0 0%
Neither Complete or Partial Metabolic Response	4 100%
Complete Metabolic Response	1 25%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	2 50%
Complete Metabolic Response	1 25%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	2 50%
Complete Metabolic Response	0 0%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	3 75%
Complete Metabolic Response	1 25%
Partial Metabolic Response	2 50%
Neither Complete or Partial Metabolic Response	1 25%
Complete Metabolic Response	1 25%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	2 50%
Complete Metabolic Response	1 25%
Partial Metabolic Response	1 25%
Neither Complete or Partial Metabolic Response	2 50%
Complete Metabolic Response	0 0%
Partial Metabolic Response	0 0%
Neither Complete or Partial Metabolic Response	4 100%
Complete Metabolic Response	0 0%
Partial Metabolic Response	0 0%
Neither Complete or Partial Metabolic Response	4 100%

3. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
SAE	0 0%
Grade 4 AE	0 0%
Grade 3 AE	1 25%
AE leading to dose interruption/reduction	4 100%

4. Secondary Outcome

Title	Six-Minute Walk Test
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	320.4 (221.8)
24 Weeks	496 (173.4)

5. Secondary Outcome

Title	Hand Grip Strength Test
Description	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

Outcome Measure Data

Analysis Population Description

Only 2 patients performed strength testing at 28 weeks.

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	14.7 (11.8)
Week 4	16.4 (11.2)
Week 8	18.5 (9.4)
Week 12	17.0 (7.9)
Week 16	22.6 (18.5)
Week 20	17.3 (6.6)
Week 24	15.5 (1.4)
Week 28	30.1 (6.7)

6. Secondary Outcome

Title	Pinch Test
Description	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

Outcome Measure Data

Analysis Population Description

Only 2 patients performed strength testing at 28 weeks.

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	6.8 (4.0)
Week 4	6.7 (1.2)
Week 8	6.8 (1.3)
Week 12	7.5 (2.0)
Week 16	7.5 (1.0)
Week 20	7.7 (1.5)
Week 24	7.0 (1.3)
Week 28	8.1 (1.9)

7. Secondary Outcome

Title	Five Times Sit-to-Stand Test
Description	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

Outcome Measure Data

Analysis Population Description

Only 2 patients performed strength testing at 28 weeks.

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	14.7 (6.5)
Week 4	13.2 (4.0)
Week 8	13.5 (1.1)
Week 12	11.2 (0.7)
Week 16	10.5 (1.5)
Week 20	10.8 (0.8)
Week 24	11.1 (0.8)
Week 28	11.1 (1.0)

8. Secondary Outcome

Title	The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH)
Description	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

Outcome Measure Data

Analysis Population Description

2 patients did not fill out their DASH at week 28

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	16.5 (4.8)
Week 4	13.3 (6.8)
Week 8	14.2 (4.6)
Week 12	13.3 (7.3)
Week 16	12.7 (6.7)
Week 20	21.0 (23.1)
Week 24	12.1 (8.1)
Week 28	10.0 (2.3)

9. Secondary Outcome

Title	RAND SF-36 Survey Results
Description	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

Outcome Measure Data

Analysis Population Description

Only 2 patients completed week 28 surveys

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Physical Functioning - Baseline	46.3 (18.9)
Physical Functioning - 4 weeks	47.5 (21.0)
Physical Functioning - 8 weeks	51.3 (16.5)
Physical Functioning - 12 weeks	47.5 (12.6)
Physical Functioning - 16 weeks	56.0 (16.2)
Physical Functioning - 20 weeks	52.5 (26.0)
Physical Functioning - 24 weeks	41.0 (6.4)
Physical Functioning - 28 weeks	65.0 (7.1)
Role limitations due to physical health problems - Baseline	43.8 (12.5)
Role limitations due to physical health problems - 4 weeks	93.8 (12.5)
Role limitations due to physical health problems - 8 weeks	68.8 (31.5)
Role limitations due to physical health problems - 12 weeks	50 (35.4)
Role limitations due to physical health problems - 16 weeks	50 (57.7)
Role limitations due to physical health problems - 20 weeks	75 (50)
Role limitations due to physical health problems - 24 weeks	25 (50)
Role limitations due to physical health problems - 28 weeks	12.5 (17.7)
Role limitations due to emotional problems - Baseline	66.7 (27.2)
Role limitations due to emotional problems - 4 weeks	83.3 (33.3)
Role limitations due to emotional problems - 8 weeks	75 (31.9)
Role limitations due to emotional problems - 12 weeks	66.7 (47.1)
Role limitations due to emotional problems - 16 weeks	50 (43)
Role limitations due to emotional problems - 20 weeks	91.7 (16.7)
Role limitations due to emotional problems - 24 weeks	41.7 (50)
Role limitations due to emotional problems - 28 weeks	33.3 (47.1)
Emotional well-being - Baseline	67 (15.1)
Emotional well-being - 4 weeks	72 (15.7)
Emotional well-being - 8 weeks	72 (12.6)
Emotional well-being - 12 weeks	72 (17.6)
Emotional well-being - 16 weeks	69.8 (21.5)
Emotional well-being - 20 weeks	73 (8.2)
Emotional well-being - 24 weeks	62 (10.1)
Emotional well-being - 28 weeks	72 (5.7)
Energy/fatigue - Baseline	50 (29.4)
Energy/fatigue - Week 4	58.8 (8.5)
Energy/fatigue - week 8	52.5 (22.2)
Energy/fatigue - week 12	46.3 (28.4)
Energy/fatigue - week 16	61.3 (31.5)
Energy/fatigue - week 20	57.5 (18.5)
Energy/fatigue - week 24	48.8 (33.3)
Energy/fatigue - week 28	47.5 (53.0)
Social functioning - Baseline	59.4 (37.3)
Social functioning - 4 weeks	87.5 (14.4)
Social functioning - 8 weeks	78.1 (21.3)
Social functioning - 12 weeks	81.3 (16.1)
Social functioning - 16 weeks	75 (27)
Social functioning - 20 weeks	78.1 (25.8)
Social functioning - 24 weeks	71.9 (32.9)
Social functioning - 28 weeks	75 (17.7)
Bodily Pain - Baseline	51.9 (29.2)
Bodily Pain - week 4	66.3 (28)
Bodily Pain - week 8	63.1 (37.4)
Bodily Pain - week 12	43.1 (26.8)
Bodily Pain - week 16	72.5 (34.6)
Bodily Pain - week 20	75 (20.7)
Bodily Pain - week 24	36.2 (2.5)
Bodily Pain - week 28	90 (0)
General health perceptions - Baseline	60 (10.8)
General health perceptions - week 4	68.8 (13.1)
General health perceptions - week 8	72.5 (16.6)
General health perceptions - week 12	73.8 (25.9)
General health perceptions - week 16	71.3 (14.9)
General health perceptions - week 20	67.5 (23.3)
General health perceptions - week 24	71.3 (18.0)
General health perceptions - week 28	67.5 (31.8)

10. Secondary Outcome

Title	PROMIS Fatigue
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	55.1 (8.1)
Week 4	47.4 (1.6)
Week 8	52.6 (7.9)
Week 12	52.3 (9.1)
Week 16	52.3 (9.1)
Week 20	46.6 (9.1)
Week 24	52 (4.9)
Week 28	46.7 (8.1)

11. Secondary Outcome

Title	PROMIS Pain Interference Score
Description	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

Outcome Measure Data

Analysis Population Description

Only 2 patients completed the week 28 surveys

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	56.4 (4.5)
Week 4	52.6 (9.4)
Week 8	52.5 (6.0)
Week 12	55.7 (4.2)
Week 16	49.0 (10.6)
Week 20	48.2 (15)
Week 24	52.6 (9.1)
Week 28	40.7 (0)

12. Secondary Outcome

Title	PROMIS Mobility Score
Description	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

Outcome Measure Data

Analysis Population Description

Only 2 patients completed the week 28 surveys

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	38.2 (6.7)
Week 4	40.0 (6.4)
Week 8	39.3 (5.3)
Week 12	38.8 (3.2)
Week 16	40.2 (4.5)
Week 20	40.7 (7.3)
Week 24	39.5 (2.6)
Week 28	43.6 (1.6)

13. Secondary Outcome

Title	Blood Intact FGF23 Levels
Description	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

Outcome Measure Data

Analysis Population Description

There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples.

Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	1384 (1467)
4 Weeks	282 (254)
8 Weeks	286 (236)
12 Weeks	596 (924)
16 Weeks	310 (202)
20 Weeks	135 (67)
24 Weeks	439 (230)
Follow up	2534.8 (2824.6)

14. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	814 (911)
2 Weeks	213 (158)
4 Weeks	330 (87)
6 Weeks	229 (123)
8 Weeks	304 (154)
10 Weeks	2225 (2015)
12 Weeks	430 (409)
14 Weeks	270 (65)
16 Weeks	360 (75)
18 Weeks	185 (151)
20 Weeks	274 (118)
22 Weeks	368 (272)
24 Weeks	463 (102)
Follow up	1568 (1863)

15. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	1.6 (0.3)
Week 2	2.7 (0.9)
Week 4	2.9 (1)
Week 6	3.2 (1.3)
Week 8	3.6 (1.5)
Week 10	3.1 (0.7)
Week 12	2.9 (1.2)
Week 14	2.8 (1.2)
Week 16	3.4 (1.6)
Week 18	2.5 (0.2)
Week 20	3.0 (1.3)
Week 22	3.3 (2.8)
Week 24	3.0 (1.2)
Follow up	2.3 (0.4)

16. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	22.5 (16.1)
Week 2	112.3 (94.5)
Week 4	79 (68.4)
Week 6	202.8 (246.5)
Week 8	64.7 (30.7)
Week 10	85.7 (63.8)
Week 12	96.5 (61.4)
Week 14	59.8 (28.9)
Week 16	36 (6.1)
Week 18	86.5 (56.3)
Week 20	33 (12.1)
Week 22	22.5 (19.1)
Week 24	80.3 (35.7)
Follow up	51 (32.2)

17. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	132 (52.3)
Week 2	178.8 (50.7)
Week 4	186.5 (42.1)
Week 6	198 (36.6)
Week 8	171.8 (26.6)
Week 10	181.3 (22)
Week 12	170 (18.4)
Week 14	188.3 (29.4)
Week 16	175.5 (14.3)
Week 18	183 (40.4)
Week 20	190.3 (33.6)
Week 22	200.7 (48)
Week 24	192.3 (67.4)
Follow up	185.7 (17)

18. Secondary Outcome

Title	Tubular Reabsorption of Phosphate
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	67 (20)
Week 2	82 (13)
Week 4	79 (14)
Week 6	84 (14)
Week 8	78 (19)
Week 10	50 (36)
Week 12	45 (36)
Week 14	82 (15)
Week 16	81 (15)
Week 18	77 (13)
Week 20	75 (12)
Week 22	81 (11)
Week 24	74 (19)

19. Secondary Outcome

Title	Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
Measure Participants	4
Baseline	1.1 (0.5)
Week 2	2.5 (1.2)
Week 4	2.3 (1.3)
Week 6	3.5 (2.2)
Week 8	3.4 (2.3)
Week 10	1.32 (0.9)
Week 12	1.52 (1.86)
Week 14	2.76 (1.61)
Week 16	3.44 (2.47)
Week 18	1.98 (0.34)
Week 20	2.31 (1.25)
Week 22	3.86 (2.99)
Week 24	2.61 (1.87)

20. Secondary Outcome

Title	Radiographic Evidence of Tumor-Induced Osteomalacia
Description	In patients with radiographic evidence of TIO, 18FDG PET scans were performed
Time Frame	Baseline and at 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TIO Subjects With Radiographic Evidence of TIO Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects with radiographic evidence of TIO were treated with BGJ398 for 24 weeks with optional extension phase. FDG-PET imaging was performed at baseline and at week 24.
Measure Participants	2
Baseline SUVmax Tumor	7.9 (1.3)
24 Week SUVmax tumor	3.9 (1.3)

Adverse Events

Time Frame	Patients were monitored for adverse events during 24 weeks of treatment followed by 3 month follow-up period, with optional extension phase up to 37 weeks. If a patient was withdrawn from the study, adverse event data was no longer collected. Subjects who required permanent discontinuation of BGJ398 therapy due to an adverse event continued to be followed in the study until the toxicity had resolved or up to 30 days after study drug discontinuation.
Adverse Event Reporting Description	Adverse Events information was collected through investigator assessment every 4 weeks and labs every 2 weeks while on treatment. During the extension phase, adverse event information was collected through investigator and lab assessment every 4 weeks.
Arm/Group Title	TIO Subjects Who Received BGJ398 (Single Arm)
Arm/Group Description	TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase
All Cause Mortality
	TIO Subjects Who Received BGJ398 (Single Arm)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	TIO Subjects Who Received BGJ398 (Single Arm)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	TIO Subjects Who Received BGJ398 (Single Arm)
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Blood and lymphatic system disorders
Anemia	1/4 (25%)
Ear and labyrinth disorders
Ear Pain	1/4 (25%)
Hearing impairment	1/4 (25%)
Hypertrichosis of eyelashes	2/4 (50%)
Eye disorders
Blurred vision	4/4 (100%)
Dry eye	3/4 (75%)
Corneal inflamation/keratitis	4/4 (100%)
Nuclear Sclerosis	1/4 (25%)
Glaucoma	1/4 (25%)
Gastrointestinal disorders
Vomiting	2/4 (50%)
Nausea	1/4 (25%)
Mucositis	2/4 (50%)
Dysgeusia	2/4 (50%)
Dry mouth	3/4 (75%)
Diarrhea	2/4 (50%)
Gastroesophageal reflux	1/4 (25%)
Infections and infestations
Rash, pustular	2/4 (50%)
C. difficile colitis	1/4 (25%)
Pelvic Infection	1/4 (25%)
Investigations
Alanine aminotransferase increased	2/4 (50%)
Aspartate aminotransferase increased	1/4 (25%)
Platelet count decreased	2/4 (50%)
Lymphocyte count decreased	3/4 (75%)
Neutrophil count decreased	1/4 (25%)
Parathyroid hormone increased	3/4 (75%)
Creatinine increased	1/4 (25%)
Hypercalcemia	1/4 (25%)
Hypercalciuria	1/4 (25%)
Hyperphosphatemia	3/4 (75%)
Weight loss	1/4 (25%)
Musculoskeletal and connective tissue disorders
Pain, musculoskeletal	3/4 (75%)
Nervous system disorders
Headache	1/4 (25%)
Paresthesia	1/4 (25%)
Psychiatric disorders
Insomnia	1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/4 (50%)
Skin and subcutaneous tissue disorders
Alopecia	1/4 (25%)
Dry lips	1/4 (25%)
Pain, nails	4/4 (100%)
Nail change/separation	4/4 (100%)
Dry skin	1/4 (25%)

Limitations/Caveats

This study was terminated early due to a lack of efficacy in the first 4 patients and an unexpectedly high rate of ocular adverse events. As a result, only 4 patients were enrolled in this study. Because of the small sample size, we were unable to perform the planned statistical analysis, and instead the results are primarily descriptive.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.