A Study of KRN23 in Subjects With Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome

NCT02722798 | Completed Phase 2 DMC

• 1 other identifier: KRN23-002
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 3

Brief Summary

Before switching to the post-marketing study: To evaluate the efficacy and safety of KRN23 after its 144-week once every 4 weeks (Q4W) repeated SC administration to Japanese and Korean patients with TIO or ENS by a multicenter, open-label, intraindividual dose adjustment study. After switching to the post-marketing study: To evaluate the safety and efficacy of KRN23, which is switched from the investigational product to the post-marketing investigational product, at the approved dose and dosing regimen in subjects who continue treatment after the marketing approval of KRN23 in Japan.

Conditions

Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome

Outcome Measures

Primary Outcomes (1)

• serum phosphorus concentration at each test time point

  up to week 224

Secondary Outcomes (22)

• Change from Baseline in Serum Phosphorus Level

  up to week 224

• Achievement Proportion of Mid-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])

  at week 24

• Achievement Proportion of End-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])

  at week 48

• Changes from baseline over time in serum Type I Collagen C-Telopeptides (CTx)

  up to week 224

• Changes from baseline over time in serum Procollagen 1 N-Terminal Propeptide (P1NP)

  up to week 224

Other Outcomes (1)

• Number and types of adverse events

  up to week 224

Study Arms (1)

KRN23

EXPERIMENTAL

Subjects will receive subcutaneous injections of KRN23 every 4 weeks from Week 0 through Week 224

Drug: KRN23

Interventions

KRN23 DRUG

Doses may be titrated to achieve the target peak serum phosphorus range

KRN23

Eligibility Criteria

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

You may qualify if:

• Aged ≥ 18 years
• Diagnosis of Tumor-Induced Osteomalacia(TIO) or Epidermal Nevus Syndrome(ENS) and not amenable to receive surgical excision of the offending tumor/lesion
• Serum phosphorus level \< 2.5 mg/dL
• Serum FGF23 level ≥ 100 pg/mL
• Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate\< 2.5 mg/dL
• Estimated glomerular filtration rate (eGFR) at screening ≥ 60 mL/min/1.73 m2, or eGFR ≥ 30 and \< 60 mL/min/1.73 m2 with an evidence of no renal failure related to nephrocalcinosis
• Corrected serum calcium level \< 10.8 mg/dL
• For female subjects of childbearing potential; negative urine pregnancy test and willingness to undergo additional pregnancy tests during the study
• Willingness to use an acceptable method of contraception while participating in the study
• Willingness to provide access to prior medical records to determine eligibility including data on imaging tests, blood chemistry, diagnosis, medication, and surgical history
• Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by the investigator or subinvestigator

You may not qualify if:

• Use of the following drugs within 14 days prior to screening: pharmacologic vitamin D metabolites or analogs, or drugs for treating TIO/ENS including oral phosphate, aluminum hydroxide antacids, acetazolamide, or thiazide diuretics
• Medication to suppress parathyroid hormone (PTH) within 60 days prior to screening
• Blood or blood product transfusion within 60 days prior to screening
• Chemotherapy for TIO or other malignant tumors within 4 months prior to screening
• History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody
• Predisposition to infection, or history of recurrent infection or known immunodeficiency
• Pregnant or breastfeeding at screening or intention to become pregnant during the study; for male subjects, the partner's intention to become pregnant during the study
• Use of an investigational product or device within 4 months prior to screening, or planning to receive other investigational product before completing all assessments in this study
• Use of therapeutic monoclonal antibodies including KRN23 within 90 days prior to screening
• History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies
• Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator
• At the time of switching to the post-marketing study:
• Voluntary written informed consent to participate in the post-marketing study (if aged \< 20 years at the time of consent, written informed consent must be obtained from his or her legally acceptable representative as well)
• Switching to the post-marketing study is necessary and appropriate for the subject from the viewpoint of efficacy and safety, as judged by the investigator or subinvestigator.

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead

Study Sites (3)

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Unknown Facility

Seoul, South Korea

Location

MeSH Terms

Conditions

Oncogenic osteomalacia; Nevus, Sebaceous of Jadassohn

Interventions

burosumab

Condition Hierarchy (Ancestors)

Nevus; Nevi and Melanomas; Neoplasms by Histologic Type; Neoplasms; Neurocutaneous Syndromes; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

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

Study Record Dates

• First Submitted: March 7, 2016
• First Posted: March 30, 2016
• Study Start: April 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: October 1, 2020
• Last Updated: September 6, 2022

Record last verified: 2022-08

Locations

KR (1); JP (2)