A Study of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia

NCT03233126 | Completed Phase 3

• 1 other identifier: KRN23-003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

Before switching to the post-marketing study: To evaluate the efficacy and safety of KRN23 administered subcutaneously once every 2 weeks in children with X-linked hypophosphatemic rickets/osteomalacia(XLH). After switching to the post-marketing study: To evaluate the safety and efficacy of KRN23, which is switched from the investigational product to the post-marketing study drug, at the approved dose and dosing regimen in subjects who continue treatment

Conditions

X-linked Hypophosphatemic Rickets/Osteomalacia

Outcome Measures

Primary Outcomes (2)

• Number of subjects for each adverse events

  up to week 128

• Percentage of subjects for each adverse events

  up to week 128

Secondary Outcomes (25)

• Effect to body temperature

  up to week 128

• Effect to pulse rate

  up to week 128

• Effect to respiratory rate

  up to week 128

• Effect to blood pressure

  up to week 128

• Effect to 12-Lead Electrocardiogram

  up to week 128

Study Arms (1)

KRN23

EXPERIMENTAL

Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 128

Drug: KRN23

Interventions

KRN23 DRUG

Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86

KRN23

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ）Personally submitted voluntary written informed consent by a legally authorized representative.If appropriate, written or verbal assent to participate in the study should be obtained from patients.
• \) Aged ≥ 1 and ≤12 years 3）Patients who have open growth plate 4）Willing to perform a self-administration of KRN23 and available to perform a self-administration 5）Diagnosis of XLH, and meeting any of the followings;
• phosphate-regulating gene with homologies to endopeptidases on the X chromosome(PHEX) mutation in either the patient or in a directly related family member with appropriate X-linked inheritance
• Serum intact FGF23 level at screening ≥ 30 pg/mL 6） Finding evidence of rickets or clinical symptoms 7）Meeting all of following criteria for laboratory test related to XLH;
• a）Serum P: \< 3.0 mg/dL b）Serum Cr: Within the age-adjusted normal limits c）Serum 25(OH)D: ≥ 16 ng/mL 8） For female patients who have reached menarche with child bearing potential; a negative urine pregnancy test at screening 9）For female patients with child baring potential, or male patients with reproductive capacity; willingness to use an acceptable method of contraception while participating in the study 10） Willingness to provide access to prior medical records to determine eligibility including data on imaging tests, blood chemistry, diagnosis, medication, and surgical history 11） Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by the investigator or subinvestigator

You may not qualify if:

• ）Height percentile \> 50% based on age-adjusted Japanese norms at screening 2）Use of aluminum hydroxide antacids, systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to screening 3）Current or prior use of leuprorelin, triptorelin, goserelin, or other drugs known to delay puberty 4）Use of growth hormone therapy within 12 months before screening 5）Use of medication to suppress parathyroid hormone within 60 days prior to screening 6）Serum calcium levels outside the age-adjusted normal limits 7）Intact parathyroid hormone(iPTH) levels ≥ 163 pg/mL 8）Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale: 0 = Normal
• = Faint hyperechogenic rim around the medullary pyramids
• = More intense echogenic rim with echoes faintly filling the entire pyramid
• = Uniformly intense echoes throughout the pyramid
• = Stone formation: solitary focus of echoes at the tip of the pyramid 9）Planned or recommended orthopedic surgery 10）Blood or blood product transfusion within 60 days prior to screening 11）History of malignancy within 5 years prior to registration 12）History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody 13）Predisposition to infection, or history of recurrent infection or known immunodeficiency 14）Use of any investigational product or investigational medical device within 4 months prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments 15）Receiving investigational agent in the UX023-CL301 study 16）Use of a therapeutic monoclonal antibody other than KRN23 within 90 days prior to screening 17）History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies 18）Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator
• Subjects eligible for enrollment in the post-marketing clinical study must meet both of the following criteria:
• \) Personally submitted voluntary written informed consent to participate in the postmarketing clinical study by a legally authorized representative. If appropriate, written or verbal assent to participate in the post-marketing clinical study should be obtained from subjects.

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead

Study Sites (4)

Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center

Yokohama, Kanagwa, Japan

Location

Osaka Hospital, Japan Community Healthcare Organization (JCHO)

Osaka, Osaka, Japan

Location

National University Corporation Osaka University Hospital

Suita, Osaka, Japan

Location

Okayama Saiseikai General Hospital Outpatient Center

Okayama, Japan

Location

Related Publications (1)

• Kubota T, Namba N, Tanaka H, Muroya K, Imanishi Y, Takeuchi Y, Kanematsu M, Sun W, Seino Y, Ozono K. Self-Administration of Burosumab in Children and Adults with X-Linked Hypophosphataemia in Two Open-Label, Single-Arm Clinical Studies. Adv Ther. 2023 Apr;40(4):1530-1545. doi: 10.1007/s12325-022-02412-x. Epub 2023 Jan 31.

  PMID: 36719566 DERIVED

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets; Osteomalacia

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

Study Design

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

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 28, 2017
• Study Start: July 6, 2017
• Primary Completion: February 17, 2020
• Study Completion: February 17, 2020
• Last Updated: September 6, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (4)