Study of Burosumab (KRN23) in Adults With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)

NCT ID: NCT02304367

Last Updated: 2024-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-24
• Study Completion Date: 2021-01-21

Brief Summary

The primary objectives of this study are to evaluate the effect of burosumab treatment on:

• Increasing serum phosphorus levels in adults with TIO or ENS-associated osteomalacia
• Improvement in TIO/ENS-associated osteomalacia as determined by osteoid thickness (O.Th), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV) and mineralization lag time (MLt).

Conditions

Tumor Induced Osteomalacia (TIO); Epidermal Nevus Syndrome (ENS)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Burosumab

Participants received burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL.

Group Type: EXPERIMENTAL

Burosumab

Intervention Type: BIOLOGICAL

Solution for subcutaneous injection

Interventions

Burosumab

Solution for subcutaneous injection

Intervention Type: BIOLOGICAL

Other Intervention Names

KRN23; Crysvita®; UX023

Eligibility Criteria

Inclusion Criteria

1. Have a clinical diagnosis of TIO/ENS-associated osteomalacia based on evidence of excessive fibroblast growth factor 23 (FGF23) that was not amenable to cure by surgical excision of the underlying tumor/lesion (documented by Investigator).

2. Be ≥ 18 years of age

3. Have a fasting serum phosphorus level < 2.5 mg/dL

4. Have an FGF23 level ≥ 100 pg/mL by Kainos assay

5. Have a ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) < 2.5 mg/dL

6. Have an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using Cockcroft-Gault formula). Subjects with eGFR ≥ 30 but < 60 mL/min will be considered eligible as long as in the opinion of the investigator the decline in renal function is not related to nephrocalcinosis.

7. Have a corrected serum calcium level < 10.8 mg/dL

8. Females of child-bearing potential must have a negative urine pregnancy test at Screening and Baseline and be willing to have additional pregnancy tests during the study. Females considered not to be of childbearing potential include those who have not experienced menarche, are post-menopausal (defined as having no menses for at least 12 months without an alternative medical cause) or are permanently sterile due to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.

9. Be willing to use 2 forms of effective methods of contraception while participating in the study (sexually active subjects) and for 12 weeks after last dose of study drug.

10. Be willing to provide access to prior medical records to determine eligibility including imaging, biochemical, and diagnostic, medical, and surgical history data

11. Provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures

12. Be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments (in the opinion of the investigator)

Exclusion Criteria

1. Have a prior diagnosis of human immunodeficiency virus (HIV), hepatitis B and/or hepatitis C

2. Have a history of recurrent infection, a predisposition to infection, or a known immunodeficiency

3. Are pregnant or breastfeeding at Screening or are planning to become pregnant (self or partner) at any time during the study

4. Have participated in an investigational drug or device trial within 30 days prior to Screening or are currently enrolled in another study of an investigational product or device

5. Have used a therapeutic monoclonal antibody (mAb), including KRN23, within 90 days prior to Screening or have a history of allergic or anaphylactic reactions to any mAb

6. Have or a have a history of any hypersensitivity to KRN23 excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects

7. Have used a pharmacologic vitamin D metabolite or its analog (e.g., calcitriol, doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g., Maalox® and Mylanta®) within 2 weeks prior to Screening or during the study

8. Have used medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening

9. Have a history of malignancy within 5 years of study entry with the exception of phosphaturic mesenchymal tumors (PMTs) of the mixed connective tissue type or non-melanoma skin cancers such as basal cell skin cancer

10. Have donated blood or blood products within 60 days prior to Screening

11. Have a history of allergic reaction to or have shown adverse reactions to a tetracycline (e.g., tetracycline hydrochloride [HCl] and demeclocycline), benzodiazepines, fentanyl or lidocaine

12. Have any condition, which in the opinion of the investigator and sponsor, could present a concern for either subject safety or difficulty with data interpretation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyowa Kirin, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

Colorado Center for Bone Research at Panorama Orthopedics and Spine Center

Golden, Colorado, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Indiana University Hospital

Indianapolis, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Duke University

Durham, North Carolina, United States

Houston Methodist Research Institute

Houston, Texas, United States

Countries

United States

References

Khadora M, Mughal MZ. Burosumab treatment in a child with cutaneous skeletal hypophosphatemia syndrome: A case report. Bone Rep. 2021 Oct 1;15:101138. doi: 10.1016/j.bonr.2021.101138. eCollection 2021 Dec.

Reference Type: DERIVED

PMID: 34660853 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

UX023T-CL201

Identifier Type: -

Identifier Source: org_study_id