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

NCT03581591 | Completed Phase 3 FDA Drug

• 1 other identifier: ENSKRN23.1
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypophosphatemia; Hypophosphatemic Rickets; Pain, Chronic

Outcome Measures

Primary Outcomes (1)

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

  18 months

Study Arms (1)

Primary; open label

EXPERIMENTAL

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.

Biological: Burosumab

Interventions

Burosumab BIOLOGICAL

recombinant human IgG1 monoclonal antibody to fibroblast growth factor 23)

Primary; open label

Eligibility Criteria

• Age: Up to 18 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Redwood Dermatology Sciences: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

The Focus Center, PC

Clinton, Utah, 84015, United States

Location

Related Publications (4)

• 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.

  PMID: 19419316 BACKGROUND

• 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.

  PMID: 20939065 BACKGROUND

• 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.

  PMID: 24569459 BACKGROUND

• 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.

  PMID: 24006476 BACKGROUND

MeSH Terms

Conditions

Hypophosphatemia; Rickets, Hypophosphatemic; Chronic Pain

Interventions

burosumab

Condition Hierarchy (Ancestors)

Phosphorus Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jeffrey Sugarman, MD PhD

  Redwood Dermatology Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2017
• First Posted: July 10, 2018
• Study Start: January 31, 2018
• Primary Completion: December 6, 2019
• Study Completion: December 6, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

US (1)