Burosumab for CSHS

NCT03993821 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB 11746
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Burosumab (also known as the drug, Crysvita®) 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. This drug is already approved for use in patients with X-linked hypophosphatemia (XLH), but not for Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS). It is hypothesized that burosumab may provide clinical benefit to a patient with CSHS 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.

Conditions

Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS); Epidermal Nevus Syndrome

Keywords

CSHS; Cutaneous Skeletal Hypophosphatemia Syndrome; Epidermal Nevus Syndrome

Outcome Measures

Primary Outcomes (1)

• Serum Phosphorus change

  Change from baseline over 52 weeks in serum phosphorus with burosumab treatment.

  52 weeks

Secondary Outcomes (13)

• Changes in 1,25(OH)2-Vitamin D

  52 weeks

• Changes in tubular reabsorption of phosphate (TRP)

  52 weeks

• Changes in TmP/GFR (the ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate

  52 weeks

• Biomechanical Marker

  52 weeks

• 6-minute walk test

  52 weeks

Study Arms (1)

Burosumab

EXPERIMENTAL

Burosumab, which is FDA-approved for X-linked hypophosphatemic rickets, will be given monthly, for a total of 12 months and titrated to achieve a target fasting serum phosphorus level within normal range for age. The chosen starting dose of burosumab will be 0.3 mg/kg given SQ Q4W. The maximum dose allowed in this protocol is 2.0 mg/kg. Burosumab will be administered via subcutaneous (SC) route.

Drug: Burosumab

Interventions

Burosumab DRUG

Burosumab, the investigational product, is a recombinant human IgG1 monoclonal antibody targeting FGF23. It is supplied as a sterile, clear, colorless and preservative-free solution and is administered via subcutaneous injection.

Also known as: Crysvita

Burosumab

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Patient has confirmed CSHS by physician diagnosis
• Patient has confirmed FGF23 elevations in the context of a low fasting serum phosphorous \< 2.5 mg/dL
• Patient able to tolerate burosumab treatment
• Have a corrected serum calcium level \< 10.8 mg/dL
• Have an eGFR \>25 mL/min/1.73m2 (using CKD-EPI equation)
• Must be willing in the opinion of the investigators, to comply with study procedures and schedule
• Provide written informed consent by the subject or a Legal Authorized Representative (LAR) after the study has been explained and prior to any research related procedures begin
• Must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study.
• Must be willing to use a highly effective method of contraception for the duration of the study and for at least 12 weeks after the last dose of the study drug. Highly effective methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (e.g., oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (e.g., oral, injectable, implantable), intrauterine device (IUD) or intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, or sexual abstinence (i.e., refraining from heterosexual intercourse during the entire period of risk associated with the study treatments, when this is in line with the preferred and usual lifestyle of the subject)

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Concomitant use of active vitamin D (i.e. calcitriol) and/or exogenous phosphate supplementation during burosumab therapy. Subjects will be allowed over the counter Vitamin D should levels drop below \<20 ng/ml
• Blood phosphorus level within or above the normal range while not taking phosphate or active Vitamin D.
• Severe renal impairment or end-stage renal disease, defined as an eGFR of less than 25 ml/min/1.73m2
• The use or enrollment in studies using other investigational therapies including other monoclonal antibodies
• Subject or Legally Authorized Representative not willing or not able to give written informed consent
• In the investigator's opinion, the subject may not be able to meet all the requirements for study participation
• History of hypersensitivity to burosumab 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

• Laura Tosi: lead
• Children's National Research Institute: collaborator
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

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 Officials

• Laura Tosi, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is an open-label, 52-week study designed to assess the efficacy, safety and pharmacodynamics (PD) of burosumab in a single subject with cutaneous skeletal hypophosphatemia syndrome (CSHS). Burosumab (formerly 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. It is hypothesized that burosumab may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with X-linked hypophosphatemia (in whom burosumab is FDA-approved) - abnormally elevated FGF23, in the context of low age-adjusted serum phosphorous levels. Patient will be seen at Screening, Baseline and every 2-4 wks, as described in "Schedule of Activities"

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: June 21, 2019
• Study Start: July 1, 2019
• Primary Completion: October 30, 2022
• Study Completion: March 1, 2023
• Last Updated: March 7, 2022

Record last verified: 2022-03

Locations

US (1)