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

NCT04320316 | Completed Phase 4 Results FDA Drug

• 1 other identifier: IRB-300004900
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Epidermal Nevus Syndrome

Keywords

epidermal nevus syndrome; burosumab-twza

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.

  1 year

• Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.

  every 3 months, From Baseline to 52 weeks

• Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.

  every 3 months, From Baseline to 52 weeks

• Participant Will Achieve Improvement of Underlying Skeletal Disease/Rickets as Assessed by Standard Radiographs.

  baseline scans prior to drug administration

• Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)

  every 3 months, From baseline to 52 weeks

Study Arms (1)

Crysvita (burosumab-twza) Treatment

EXPERIMENTAL

The starting dose will be 0.3 mg/kg to be given every 2 weeks. If required dose may be titrated with increments of 0.1 mg/kg/dose every 4 weeks up to a maximum of dose of 2.0mg/kg (not to exceed 90mg per dose) until phosphorus level is WNL. Patient will receive study drug via SC injection to the abdomen, upper arms, thighs, or buttocks; the injection site will be rotated with each injection. If the dose level exceeds 1.5 mL in volume, the dose should be administered at two injection sites. Duration of treatment is 52 weeks. Subjects that complete treatment through week 52 may have the option to continue KRN23 treatment. If this is warranted based on preliminary efficacy, the current protocol will be amended to allow for an extension.

Drug: Crysvita (burosumab-twza) Treatment

Interventions

Crysvita (burosumab-twza) Treatment DRUG

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.

Also known as: no other names available

Crysvita (burosumab-twza) Treatment

Eligibility Criteria

• Age: 6 Months+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Related Publications (1)

• Huynh C, Gillis A, Fazendin J, Abdullatif H. A case report to assess the safety and efficacy of Burosumab, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome and associated hypophosphatemic rickets. Bone Rep. 2022 Jul 20;17:101605. doi: 10.1016/j.bonr.2022.101605. eCollection 2022 Dec.

  PMID: 35899095 DERIVED

MeSH Terms

Conditions

Nevus, Sebaceous of Jadassohn

Interventions

burosumab; Therapeutics

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

Limitations and Caveats

The patient is wheel chair bound and so we could not obtain data on mobility before or after the trial. We were not able to check a DEXA scan at the end of the study either.

Results Point of Contact

• Title: M.D
• Organization: University of Alabama at Birmingham

hdabdullatif@uabmc.edu

12056389107

Study Officials

• Hussein Abdul-Latif, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: March 25, 2020
• Study Start: July 31, 2020
• Primary Completion: July 31, 2021
• Study Completion: August 31, 2021
• Last Updated: October 7, 2022
• Results First Posted: October 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)