BGJ398 for the Treatment of Tumor-Induced Osteomalacia

NCT03510455 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 18008618-D-0086
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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....

Conditions

Tumor-Induced Osteomalacia; Oncogenic Osteomalacia

Keywords

FGF-23; Fibroblast Growth Factor (FGF23); Hypophosphatemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 weeks after stopping BGJ398

Secondary Outcomes (19)

• Number of Participants With Complete and Partial Metabolic Response Rate

  Every 2 weeks up to 24 weeks

• 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

• Six-Minute Walk Test

  Assessed at baseline and 24 weeks after starting BGJ398

• 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

• 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

Study Arms (1)

Single Arm (TIO Subjects)

EXPERIMENTAL

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

Interventions

BGJ398 DRUG

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.

Single Arm (TIO Subjects)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Oncogenic osteomalacia; Hypophosphatemia

Interventions

infigratinib

Condition Hierarchy (Ancestors)

Phosphorus Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and 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.

Results Point of Contact

• Title: Rachel I. Gafni
• Organization: National Institute of Dental and Craniofacial Research

gafnir@mail.nih.gov

301-594-9924

Study Officials

• Rachel I Gafni, M.D.

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: April 27, 2018
• Study Start: February 27, 2019
• Primary Completion: February 28, 2020
• Study Completion: May 4, 2020
• Last Updated: April 8, 2021
• Results First Posted: April 8, 2021

Record last verified: 2020-05

Locations

US (1)