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NCT03510455

BGJ398 for the Treatment of Tumor-Induced Osteomalacia

Terminated Phase 2 Results posted Last updated 8 April 2021
What this trial tests

Phase 2 trial testing BGJ398 in Tumor-Induced Osteomalacia in 4 participants. Terminated before completion.

Timeline
27 February 2019
Primary endpoint
28 February 2020
4 May 2020

Quick facts

Lead sponsorNational Institute of Dental and Craniofacial Research (NIDCR)
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment4
Start date27 February 2019
Primary completion28 February 2020
Estimated completion4 May 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Dental and Craniofacial Research (NIDCR)

Who can join

Adults 18 to 85, any sex, with Tumor-Induced Osteomalacia or Oncogenic Osteomalacia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Complete Metabolic Remission After Stopping BGJ398 Primary · 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.

GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)0
TIO Subjects Who Received BGJ398 (Single Arm)4
Number of Participants With Complete and Partial Metabolic Response Rate Secondary · 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

Baseline
GroupValue95% CI
Single Arm (TIO Subjects)0
Single Arm (TIO Subjects)0
Single Arm (TIO Subjects)4
Week 2
GroupValue95% CI
Single Arm (TIO Subjects)2
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)1
Week 4
GroupValue95% CI
Single Arm (TIO Subjects)0
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)3
Week 6
GroupValue95% CI
Single Arm (TIO Subjects)2
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)1
Week 8
GroupValue95% CI
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)2
Week 10
GroupValue95% CI
Single Arm (TIO Subjects)0
Single Arm (TIO Subjects)0
Single Arm (TIO Subjects)4
Week 12
GroupValue95% CI
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)2
Week 14
GroupValue95% CI
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)1
Single Arm (TIO Subjects)2
Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events Secondary · 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

SAE
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)0
Grade 4 AE
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)0
Grade 3 AE
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)1
AE leading to dose interruption/reduction
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)4
Six-Minute Walk Test Secondary · 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.

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)320.4± 221.8
24 Weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)496± 173.4
Hand Grip Strength Test Secondary · 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

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)14.7± 11.8
Week 4
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)16.4± 11.2
Week 8
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)18.5± 9.4
Week 12
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)17.0± 7.9
Week 16
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)22.6± 18.5
Week 20
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)17.3± 6.6
Week 24
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)15.5± 1.4
Week 28
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)30.1± 6.7
Pinch Test Secondary · 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.

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)6.8± 4.0
Week 4
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)6.7± 1.2
Week 8
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)6.8± 1.3
Week 12
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)7.5± 2.0
Week 16
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)7.5± 1.0
Week 20
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)7.7± 1.5
Week 24
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)7.0± 1.3
Week 28
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)8.1± 1.9
Five Times Sit-to-Stand Test Secondary · 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

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)14.7± 6.5
Week 4
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)13.2± 4.0
Week 8
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)13.5± 1.1
Week 12
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)11.2± 0.7
Week 16
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)10.5± 1.5
Week 20
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)10.8± 0.8
Week 24
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)11.1± 0.8
Week 28
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)11.1± 1.0
The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) Secondary · 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)

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)16.5± 4.8
Week 4
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)13.3± 6.8
Week 8
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)14.2± 4.6
Week 12
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)13.3± 7.3
Week 16
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)12.7± 6.7
Week 20
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)21.0± 23.1
Week 24
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)12.1± 8.1
Week 28
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)10.0± 2.3
RAND SF-36 Survey Results Secondary · 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.

Physical Functioning - Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)46.3± 18.9
Physical Functioning - 4 weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)47.5± 21.0
Physical Functioning - 8 weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)51.3± 16.5
Physical Functioning - 12 weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)47.5± 12.6
Physical Functioning - 16 weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)56.0± 16.2
Physical Functioning - 20 weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52.5± 26.0
Physical Functioning - 24 weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)41.0± 6.4
Physical Functioning - 28 weeks
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)65.0± 7.1
PROMIS Fatigue Secondary · 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.

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)55.1± 8.1
Week 4
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)47.4± 1.6
Week 8
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52.6± 7.9
Week 12
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52.3± 9.1
Week 16
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52.3± 9.1
Week 20
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)46.6± 9.1
Week 24
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52± 4.9
Week 28
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)46.7± 8.1
PROMIS Pain Interference Score Secondary · 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

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)56.4± 4.5
Week 4
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52.6± 9.4
Week 8
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52.5± 6.0
Week 12
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)55.7± 4.2
Week 16
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)49.0± 10.6
Week 20
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)48.2± 15
Week 24
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)52.6± 9.1
Week 28
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)40.7± 0
PROMIS Mobility Score Secondary · 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)

Baseline
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)38.2± 6.7
Week 4
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)40.0± 6.4
Week 8
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)39.3± 5.3
Week 12
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)38.8± 3.2
Week 16
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)40.2± 4.5
Week 20
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)40.7± 7.3
Week 24
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)39.5± 2.6
Week 28
GroupValue95% CI
TIO Subjects Who Received BGJ398 (Single Arm)43.6± 1.6

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TIO Subjects Who Received BGJ398 (Single Arm)
Serious: 0/4 (0%)
Deaths: 0/4
Other adverse events (40 terms — click to expand)

ReactionSystemTIO Subjects Who Received …
Blurred visionEye disorders
Corneal inflamation/keratitisEye disorders
Pain, nailsSkin and subcutaneous tissue disorders
Nail change/separationSkin and subcutaneous tissue disorders
Dry eyeEye disorders
Lymphocyte count decreasedInvestigations
Parathyroid hormone increasedInvestigations
HyperphosphatemiaInvestigations
Dry mouthGastrointestinal disorders
Pain, musculoskeletalMusculoskeletal and connective tissue disorders
Hypertrichosis of eyelashesEar and labyrinth disorders
Rash, pustularInfections and infestations
Alanine aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
VomitingGastrointestinal disorders
MucositisGastrointestinal disorders
DysgeusiaGastrointestinal disorders
DiarrheaGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
AnemiaBlood and lymphatic system disorders
Ear PainEar and labyrinth disorders
Hearing impairmentEar and labyrinth disorders
Nuclear SclerosisEye disorders
GlaucomaEye disorders
C. difficile colitisInfections and infestations
Pelvic InfectionInfections and infestations
Aspartate aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
Creatinine increasedInvestigations
HypercalcemiaInvestigations
HypercalciuriaInvestigations
Weight lossInvestigations
NauseaGastrointestinal disorders
Gastroesophageal refluxGastrointestinal disorders
HeadacheNervous system disorders
ParesthesiaNervous system disorders
InsomniaPsychiatric disorders
AlopeciaSkin and subcutaneous tissue disorders
Dry lipsSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT03510455 adverse events section.

Sponsor's own description

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....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.
    Fleishman JS, Kumar S. · · 2024 · cited 267× · PMID 38664391 · DOI 10.1038/s41392-024-01811-6
  2. Structure, activation and dysregulation of fibroblast growth factor receptor kinases: perspectives for clinical targeting.
    Farrell B, Breeze AL. · · 2018 · cited 77× · PMID 30545934 · DOI 10.1042/bst20180004
  3. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia.
    Jan de Beur SM, Minisola S, Xia WB, Abrahamsen B, et al · · 2023 · cited 62× · PMID 36511653 · DOI 10.1111/joim.13593
  4. Targeted FGFR Blockade for the Treatment of Tumor-Induced Osteomalacia.
    Hartley IR, Miller CB, Papadakis GZ, Bergwitz C, et al · · 2020 · cited 28× · PMID 32905668 · DOI 10.1056/nejmc2020399
  5. Fibroblast Growth Factor Receptor (FGFR) Signaling in GIST and Soft Tissue Sarcomas.
    Napolitano A, Ostler AE, Jones RL, Huang PH. · · 2021 · cited 24× · PMID 34204560 · DOI 10.3390/cells10061533
  6. Infigratinib Reduces Fibroblast Growth Factor 23 (FGF23) and Increases Blood Phosphate in Tumor-Induced Osteomalacia.
    Hartley IR, Roszko KL, Li X, Pozo K, et al · · 2022 · cited 18× · PMID 35991529 · DOI 10.1002/jbm4.10661
  7. Novel Regulatory Factors and Small-Molecule Inhibitors of FGFR4 in Cancer.
    Liu Y, Wang C, Li J, Zhu J, et al · · 2021 · cited 16× · PMID 33981224 · DOI 10.3389/fphar.2021.633453
  8. Ocular Adverse Effects of Infigratinib, a New Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibitor.
    Magone MT, Hartley IR, Fitzgibbon E, Bishop R, et al · · 2021 · cited 15× · PMID 32888946 · DOI 10.1016/j.ophtha.2020.08.026

Verify or expand the search:

Other trials of BGJ398

Trials testing the same drug.

Other recruiting trials for Tumor-Induced Osteomalacia

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