Tumor-induced Osteomalacia Disease Monitoring Program

Tumor-induced Osteomalacia Disease Monitoring Program (TIO DMP)

The objectives of this observational study are to assess the long-term safety and long-term effectiveness of burosumab in patients with TIO who are being treated with burosumab as prescribed by their physician and to monitor the course of the underlying phosphaturic mesenchymal tumor (PMT) overtime in patients with TIO irrespective of their treatment status.

Study Overview

• Status: Active, not recruiting
• Conditions: Tumor-induced Osteomalacia (TIO)
• Intervention / Treatment: Other: No intervention

Detailed Description

Enrolled patients may or may not be treated with commercially available burosumab during the TIO DMP at the discretion of their treating physician. Given the observational nature of the TIO DMP, specific treatments or supportive management will not be provided as part of the study.

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Indiana
    • Bloomington, Indiana, United States, 47405
      • Indiana University
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

May include patients who have undergone complete tumor resection and continue to have biochemical/clinical evidence of disease, patients with tumor identified, or patients in whom causative tumor has not been identified and who have been diagnosed with TIO based on biochemical/clinical symptom profile.

Patients may be treated with burosumab, or phosphate and active vitamin D metabolites/analogs, as prescribed by a physician, or maybe untreated, at any time during the TIO DMP.

Description

Inclusion Criteria:

• Have a clinical diagnosis of TIO based on the presence of an underlying PMT (confirmed by imaging) AND/OR historical documentation. Note: For adult patients with TIO in whom the causative PMT has never been located, and all pediatric patients, documented evidence of negative genetic testing for other hereditary hypophosphatemic disorders is necessary
• For patient safety, all participating female patients of child-bearing potential must be willing to have pregnancy tests prior to certain assessments performed as part of the DMP
• Be willing to provide access to prior medical records including tumor pathology reports and biopsy slides, imaging, biochemical, and diagnostic, medical, and surgical history data, if available
• Be willing and able to provide informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Be willing and able to comply with the study visit schedule and study procedures

Exclusion Criteria:

• Have a clinical diagnosis of TIO deemed to be caused by a tumor other than a PMT
• Serious medical or psychiatric comorbidity that, in the opinion of the Investigator, would present a concern for patient safety or compromise the ability to provide consent or comply with the study visit schedule and study procedures
• Less than 1 year of life expectancy (for any cause) in the opinion of the Investigator
• Concurrent enrollment in a clinical trial without prior approval from the TIO DMP Sponsor
• Undergoing treatment with burosumab for an unapproved indication

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prior TIO Burosumab Clinical Trial Participants	Other: No intervention; Access to any treatment is through authorized commercial use and not as part of this DMP
Adults Who Have Not Participated In Prior Burosumab Clinical Trials	Other: No intervention; Access to any treatment is through authorized commercial use and not as part of this DMP
Pediatrics Who Have Not Participated In Prior Burosumab Clinical Trials	Other: No intervention; Access to any treatment is through authorized commercial use and not as part of this DMP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-Term Effectiveness of Burosumab: Change From Baseline in Serum Phosporus Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in Serum 1,25(OH)2D Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in Serum Alkaline Phosphatase (ALP) Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in Serum FGF23 Over Time in Participants Not Undergoing Treatment With Burosumab		10 years
Long-Term Safety of Burosumab: Change From Baseline in Phosphaturic Mesenchymal Tumor (PMT) Size Over Time as Assessed by Tumor Imaging		10 years
Long-Term Safety of Burosumab: Number of Participants With New PMT Development as Assessed by Tumor Imaging		10 years
Long-Term Safety of Burosumab: Change From Baseline in Serum iPTH Over Time		10 years
Long-Term Safety of Burosumab: Change From Baseline in Serum Calcium Over Time		10 years
Long-Term Safety of Burosumab: Change From Baseline in Urine Calcium Over Time		10 years
Long-Term Safety of Burosumab: Change From Baseline Urinary Calcium/Creatinine Ratio		10 years
Long-Term Safety of Burosumab: Change From Baseline in Serum Creatinine Over Time		10 years
Long-Term Safety of Burosumab: Change From Baseline in Urine Creatinine Over Time		10 years
Long-Term Safety of Burosumab: Change From Baseline in Urine Protein/Creatinine Ratio Over Time		10 years
Long-Term Safety of Burosumab: Number of Participants With Nephrocalcinosis Over Time		10 years
Long-Term Safety of Burosumab: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) and Related AEs		10 years
Long-Term Safety of Burosumab: Number of Participants With Incidence and/or Progression of Spinal Stenosis Over Time		10 years
Long-Term Safety of Burosumab: Number of Participants With Normal and/or Potentially Clinically Significant Pregnancy Outcomes	Includes maternal, neonatal and infant outcomes	10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in Brief Fatigue Inventory (BFI) Scores in Adult Participants Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scores in Pediatric Participants Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in Brief Pain Inventory (BPI) Scores in Adult Participants Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in PROMIS Pain Scores in Pediatric Participants Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in PROMIS Physical Function Scores Over Time		10 years
Long-Term Effectiveness of Burosumab: Change From Baseline in Short Form-36 version 2 (SF-36v2) in Adult Participants Over Time		10 years
Long-Term Effectiveness of Burosumab: Change in Short Form-10 (SF-10) for Pediatric Participants Over Time		10 years
Long-Term Effectiveness of Burosumab: Number of Participants With Changes From Baseline in Clinical Findings		10 years
Long-Term Effectiveness of Burosumab: Number of Participants With Changes From Baseline in Resource/Health Utilization		10 years

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Publications and helpful links

Helpful Links

• Ultragenyx Patient Advocacy/TIO Disease Information

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Estimated): February 28, 2032
• Study Completion (Estimated): February 28, 2032

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Nutrition Disorders; Musculoskeletal Diseases; Connective Tissue Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Rickets; Vitamin D Deficiency; Osteomalacia; Neoplasms, Connective Tissue
• Other Study ID Numbers: UX023T-CL403

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No