A Trial to Assess the Safety and Efficacy of KRN23 in Epidermal Nevus Syndrome (ENS)

Epidermal Nevus Syndrome Clinical Trial

— ENS  

Official title:

An Open Label Trial to Assess the Safety and Efficacy of KRN23, an Investigational Antibody to FGF23, in a Single Pediatric Patient With Epidermal Nevus Syndrome (ENS) and Associated Hypophosphatemic Rickets

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04320316
• Other study ID #: IRB-300004900
• Status: Completed
• Phase: Phase 4
• Start date: July 31, 2020
• Est. completion date: August 31, 2021

Study information

• Verified date: September 2022
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

KRN23 is a fully human immunoglobulin monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. There are multiple disorders that result in unusually high circulating levels of FGF23, which in turn result in renal phosphate wasting and reduced levels of 1,25-dihydroxy vitamin D (1,25[OH]2D). Across these disorders the clinical symptoms are similar and often include osteomalacia (and, in children, rickets), muscle weakness, fatigue, bone pain, and fractures. KRN23 has been studied in one of these disorders, X-linked hypophosphatemia (XLH). In single- and repeat-dose clinical studies in subjects with XLH, subcutaneous (SC) administration of KRN23 consistently increased and sustained serum phosphorus levels and tubular reabsorption of phosphate (TRP) without a major impact on urine calcium levels or vitamin D metabolism. Positive results were also observed in a nonclinical pharmacology model of XLH. It is hypothesized that KRN23 may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels. The primary objective is to study the effect of KRN23 treatment on normalizing age-adjusted fasting serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets.

Description:

KRN23 is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. There are multiple disorders (each with a unique underlying cause) that result in unusually high circulating levels of FGF23, which in turn result in renal phosphate wasting and reduced (or aberrantly normal in relationship to elevated FGF23) levels of 1,25-dihydroxy vitamin D (1,25[OH]2D). Across these disorders the clinical symptoms are similar and often include osteomalacia (and, in children, rickets), muscle weakness, fatigue, bone pain, and fractures. KRN23 has been studied in one of these disorders, X-linked hypophosphatemia (XLH). In single- and repeat-dose clinical studies in subjects with XLH, subcutaneous (SC) administration of KRN23 consistently increased and sustained serum phosphorus levels and tubular reabsorption of phosphate (TRP) without a major impact on urine calcium levels or vitamin D metabolism. Positive results were also observed in a nonclinical pharmacology model of XLH. It is hypothesized that KRN23 may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: August 31, 2021
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Months and older

Eligibility

Inclusion Criteria:

• Patient has confirmed ENS by physician diagnosis

• Patient has confirmed FGF23 elevations in the context of low serum phosphorous < 4.1 mg/dL

• Patient able to tolerate KRN23 treatment

• Have a corrected serum calcium level < 10.8mg/dL

• Have an eGFR >60 ml/min

• Must be willing in the opinion of the investigator, to comply with study procedures and schedule

• Provide written informed consent by a parent after

Exclusion Criteria:

• Patient should not use CRYSVITA with Oral phosphate or active Vitamin D analogs.

• Patient and investigator should not initiate CRYSVITA if Phosphorus level is within or above normal.

• CRYSVITA is contraindicated in patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism.

• The use or enrollment in studies using other investigational therapies including other monoclonal antibodies

• Subject and their Parent not willing or not able to give written informed consent

• In the Investigators opinion, the subject may not be able to meet all the requirements for study participation

• Subject has a history of hypersensitivity to KRN23 excipients that in the opinion of the investigator, places the subject at an increased risk of adverse effects

• Subject has a condition that in the opinion of the investigator could present a concern for subject safety or data interpretation.

Related Conditions & MeSH terms

• Epidermal Nevus Syndrome
• Nevus
• Syndrome

Intervention

Drug:
• Crysvita (burosumab-twza) Treatment
KRN23 is a fully human IgG1monoclonal antibody that binds to and inhibits the activity of FGF23, leading to an increase in serum phosphorus levels. It is a potential therapeutic candidate for the treatment of XLH, Tumor-Induced Osteomalacia (TIO), and the rickets/osteomalacia resulting from Epidermal Nevus Syndrome (ENS). All of these conditions are diseases of bone hypomineralization, caused by urinary phosphate wasting due to elevated levels of FGF23.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Ultragenyx Pharmaceutical Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values	Checking PO4 levels every two weeks and adjusting doses every 4 weeks in blood	every 2 week, from baseline to 52 weeks.
Secondary	Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.	check Vitamin D 1,25 in blood every 3 months	1 year
Secondary	Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.	measure PTH levels approximately every 3 months	every 3 months, From Baseline to 52 weeks
Secondary	Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.	measure Calcium level every 3 months	every 3 months, From Baseline to 52 weeks
Secondary	Participant Will Achieve Improvement of Underlying Skeletal Disease/Rickets as Assessed by Standard Radiographs.	DEXA (dual energy X-ray Absorbometry) scans and whole body x-rays will be taken at baseline. A lower Z score is indicative of poor results. Z score compares the standard deviations of the reading with matched aged persons. The normal range is +2 to - 2 Standard deviations and those are what we call Z scores. A Z score of 0 is the population mean.	baseline scans prior to drug administration
Secondary	Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)	obtain Alkaline phosphatase in blood every 3 months	every 3 months, From baseline to 52 weeks