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Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets

Primary Purpose

Hypophosphatemia, Hypophosphatemic Rickets, Pain, Chronic

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Burosumab

About this trial

This is an interventional treatment trial for Hypophosphatemia

Eligibility Criteria

undefined - 18 Years (Child, Adult)FemaleDoes not accept healthy volunteers

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 the study has been explained and prior to any research related procedures begin

Exclusion Criteria:

Concomitant use of active vitamin D (i.e calcitriol) and/or exogenous phosphate supplementation. Patient will be allowed OTC Vitamin D should levels drop below <20 ng/ml
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 patient may not be able to meet all the requirements for study participation
Patient has a history of hypersensitivity to KRN23 excipients that in the opinion of the investigator, places the patient at an increased risk of adverse effects
Patient has a condition that in the opinion of the investigator could present a concern for subject safety or data interpretation.

Sites / Locations

The Focus Center, PC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Primary; open label

Arm Description

Injection of Burosumab every two to three weeks based on Serum Phosphorus level of subject. Initial dose to be 0.3 mg/kg. Subsequent dosing will be titrated up or down depending on Serum Phosphorus level for that time period.

Outcomes

Primary Outcome Measures

The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets

Secondary Outcome Measures

Full Information

NCT ID

NCT03581591

First Posted

October 27, 2017

Last Updated

January 14, 2020

Sponsor

Redwood Dermatology Sciences

Collaborators

Ultragenyx Pharmaceutical Inc

1. Study Identification

Unique Protocol Identification Number

NCT03581591

Brief Title

Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

January 31, 2018 (Actual)

Primary Completion Date

December 6, 2019 (Actual)

Study Completion Date

December 6, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Redwood Dermatology Sciences

Collaborators

Ultragenyx Pharmaceutical Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

A 52 week, 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 A 26 weeks extension to original study to monitor patient lab results for her safety.

Detailed Description

1.1 Primary Objective The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets 1.2 Secondary Objectives The PD profile of KRN23 as assessed by changes from baseline over time 1,25(OH)2D, iPTH, Serum Calcium, TRP and TmP/GFR (the ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate) Changes in underlying skeletal disease/rickets as assessed by standard radiographs utilizing the Radiographic Global Impression of Change (RGI-C) rating scales Effects of KRN23 on biochemical markers of bone turnover that reflect rickets severity, alkaline phosphatase (ALP) Walking ability as assessed by 6-Minute Walk Test (6MWT) Patient/parent-Reported Outcomes as assessed by PROMIS and FPS-R rating scales 1.3 Exploratory Objective 1. Dual-energy X-ray absorptiometry (DXA) 1.4 Safety Objective Assess the safety of KRN23 administration in a single patient with ENS-associated hypophosphatemic rickets, based on adverse events (AEs), laboratory assessments, cardiac imaging and renal ultrasound.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypophosphatemia, Hypophosphatemic Rickets, Pain, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Primary; open label

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Burosumab

Intervention Description

recombinant human IgG1 monoclonal antibody to fibroblast growth factor 23)

Primary Outcome Measure Information:

Title

The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets

Time Frame

18 months

10. Eligibility

Sex

Female

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 the study has been explained and prior to any research related procedures begin Exclusion Criteria: Concomitant use of active vitamin D (i.e calcitriol) and/or exogenous phosphate supplementation. Patient will be allowed OTC Vitamin D should levels drop below <20 ng/ml 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 patient may not be able to meet all the requirements for study participation Patient has a history of hypersensitivity to KRN23 excipients that in the opinion of the investigator, places the patient at an increased risk of adverse effects Patient has a condition that in the opinion of the investigator could present a concern for subject safety or data interpretation.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey Sugarman, MD PhD

Organizational Affiliation

Redwood Dermatology Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Focus Center, PC

City

Clinton

State/Province

Utah

ZIP/Postal Code

84015

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19419316

Citation

Aono Y, Yamazaki Y, Yasutake J, Kawata T, Hasegawa H, Urakawa I, Fujita T, Wada M, Yamashita T, Fukumoto S, Shimada T. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. J Bone Miner Res. 2009 Nov;24(11):1879-88. doi: 10.1359/jbmr.090509.

Results Reference

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PubMed Identifier

20939065

Citation

Aono Y, Hasegawa H, Yamazaki Y, Shimada T, Fujita T, Yamashita T, Fukumoto S. Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice. J Bone Miner Res. 2011 Apr;26(4):803-10. doi: 10.1002/jbmr.275.

Results Reference

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PubMed Identifier

24569459

Citation

Carpenter TO, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Wooddell MM, Kawakami T, Ito T, Zhang X, Humphrey J, Insogna KL, Peacock M. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. J Clin Invest. 2014 Apr;124(4):1587-97. doi: 10.1172/JCI72829. Epub 2014 Feb 24.

Results Reference

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PubMed Identifier

24006476

Citation

Lim YH, Ovejero D, Sugarman JS, Deklotz CM, Maruri A, Eichenfield LF, Kelley PK, Juppner H, Gottschalk M, Tifft CJ, Gafni RI, Boyce AM, Cowen EW, Bhattacharyya N, Guthrie LC, Gahl WA, Golas G, Loring EC, Overton JD, Mane SM, Lifton RP, Levy ML, Collins MT, Choate KA. Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia. Hum Mol Genet. 2014 Jan 15;23(2):397-407. doi: 10.1093/hmg/ddt429. Epub 2013 Sep 4.

Results Reference

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Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets

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