Study of the Safety, Pharmacodynamics (PD) and Efficacy of KRN23 in Children From 1 to 4 Years Old With X-linked Hypophosphatemia (XLH)

NCT02750618 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: UX023-CL205
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objectives of the study are to:

• Establish the safety profile of KRN23 for the treatment of XLH in children between 1 and 4 years old
• Determine the PD effects of KRN23 treatment on serum phosphorus and other PD markers that reflect the status of phosphate homeostasis in children between 1 and 4 years old with XLH

Conditions

X-Linked Hypophosphatemia

Outcome Measures

Primary Outcomes (2)

• Change From Baseline at Week 40 in Serum Phosphorus

  The Generalized Estimation Equation (GEE) model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with exchangeable covariance structure.

  Baseline, Week 40

• Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation

  An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. A serious AE was defined as an AE that at any dose, in the view of either the Investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or disability, a congenital anomaly/birth defect, or other important medical events (according to the investigator). An AE was considered a TEAE if it occurred on or after the first dose and was not present prior to the first dose, or it was present prior to the first dose but increased in severity during the study. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

  From first dose of study drug through the end of the study (Week 160). Maximum duration of exposure to study drug was 160 weeks.

Secondary Outcomes (11)

• Radiographic Global Impression of Change (RGI-C) Score at Week 40

  Week 40

• RGI-C Score at Week 64

  Week 64

• Change From Baseline in Rickets at Week 40 as Assessed by the RSS Total Score

  Baseline, Week 40

• Change From Baseline in Rickets at Week 64 as Assessed by the RSS Total Score

  Baseline, Week 64

• RGI-C Lower Limb Deformity Score at Week 40

  Week 40

Study Arms (1)

Burosumab Q2W

EXPERIMENTAL

Burosumab subcutaneous (SC) injections every 2 weeks (Q2W) for a total of 160 weeks.

Biological: Burosumab

Interventions

Burosumab BIOLOGICAL

solution for subcutaneous injection

Also known as: KRN23, Crysvita®, UX023

Burosumab Q2W

Eligibility Criteria

• Age: 1 Year - 4 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female, aged ≥1 year and \<5 years
• Diagnosis of XLH supported by ONE or more of the following
• Confirmed phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX) mutation in the patient or a directly related family member with appropriate X-linked inheritance
• Serum fibroblast growth factor 23 (FGF23) level \> 30 pg/mL by Kainos assay
• Biochemical findings associated with XLH including:
• Serum phosphorus \< 3.0 mg/dL (0.97 mmol/L)
• Serum creatinine within age-adjusted normal range
• Radiographic evidence of rickets
• Willing to provide access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history
• Provide written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
• Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule, and comply with the assessments

You may not qualify if:

• Unwilling to stop treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analog (e.g. calcitriol, alfacalcidol) during the screening period and for the duration of the study
• Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale: 0 = Normal, 1 = Faint hyperechogenic rim around the medullary pyramids, 2 = More intense echogenic rim with echoes faintly filling the entire pyramid, 3 = Uniformly intense echoes throughout the pyramid, 4 = Stone formation: solitary focus of echoes at the tip of the pyramid
• Planned or recommended orthopedic surgery including staples, 8-plates or osteotomy, within the clinical trial period
• Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits
• Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study
• Presence of a concurrent disease or condition that would interfere with study participation or affect safety
• History of recurrent infection or predisposition to infection, or of known immunodeficiency
• Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead

Study Sites (3)

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Shriners Hospital for Children

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Mao M, Carpenter TO, Whyte MP, Skrinar A, Chen CY, San Martin J, Rogol AD. Growth Curves for Children with X-linked Hypophosphatemia. J Clin Endocrinol Metab. 2020 Oct 1;105(10):3243-9. doi: 10.1210/clinem/dgaa495.

  PMID: 32721016 DERIVED

• Whyte MP, Carpenter TO, Gottesman GS, Mao M, Skrinar A, San Martin J, Imel EA. Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019 Mar;7(3):189-199. doi: 10.1016/S2213-8587(18)30338-3. Epub 2019 Jan 9.

  PMID: 30638856 DERIVED

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets

Interventions

burosumab

Condition Hierarchy (Ancestors)

Rickets, Hypophosphatemic; Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Hypophosphatemia; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8657

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 6, 2015
• First Posted: April 25, 2016
• Study Start: May 5, 2016
• Primary Completion: April 20, 2017
• Study Completion: September 10, 2019
• Last Updated: May 6, 2024
• Results First Posted: June 19, 2018

Record last verified: 2024-05

Locations

US (3)