Clinical trial NCT03581591: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypophosphatemia
Hypophosphatemic Rickets
Pain, Chronic
Lead sponsor: Redwood Dermatology Sciences
Sponsor class: OTHER
Collaborators: name: Ultragenyx Pharmaceutical Inc
First posted: 2018-07-10
Enrollment: 1
Sex: FEMALE
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

1. 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)
2. Changes in underlying skeletal disease/rickets as assessed by standard radiographs utilizing the Radiographic Global Impression of Change (RGI-C) rating scales
3. Effects of KRN23 on biochemical markers of bone turnover that reflect rickets severity, alkaline phosphatase (ALP)
4. Walking ability as assessed by 6-Minute Walk Test (6MWT)
5. 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.

Eligibility criteria: Inclusion Criteria:

1. Patient has confirmed ENS by physician diagnosis
2. Patient has confirmed FGF23 elevations in the context of low serum phosphorous \< 4.1 mg/dL
3. Patient able to tolerate KRN23 treatment
4. Have a corrected serum calcium level \< 10.8mg/dL
5. Have an eGFR \>60 ml/min
6. Must be willing in the opinion of the investigator, to comply with study procedures and schedule
7. Provide written informed consent by a parent after the study has been explained and prior to any research related procedures begin

Exclusion Criteria:

1. 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
2. The use or enrollment in studies using other investigational therapies including other monoclonal antibodies
3. Subject and their parent not willing or not able to give written informed consent
4. In the Investigators opinion, the patient may not be able to meet all the requirements for study participation
5. 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
6. Patient has a condition that in the opinion of the investigator could present a concern for subject safety or data interpretation.

Primary outcomes:
measure: The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Clinton
country: United States
facility: The Focus Center, PC
state: Utah
Study officials:
affiliation: Redwood Dermatology Sciences
name: Jeffrey Sugarman, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.