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

A Phase 3 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia and a Postmarketing Study of KRN23 Switched From the Phase 3 Trial

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

Study Overview

• Status: Completed
• Conditions: X-linked Hypophosphatemic Rickets/Osteomalacia
• Intervention / Treatment: Drug: KRN23

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Okayama, Japan
    • Okayama Saiseikai General Hospital Outpatient Center
  • Kanagwa
    • Yokohama, Kanagwa, Japan
      • Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center
  • Osaka
    • Suita, Osaka, Japan
      • National University Corporation Osaka University Hospital
    • Ōsaka, Osaka, Japan
      • Osaka Hospital, Japan Community Healthcare Organization (JCHO)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1）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.

2) 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;

1. 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
2. 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

Exclusion Criteria:

1）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

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 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:

1) 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KRN23; Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 128	Drug: KRN23; Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects for each adverse events	up to week 128
Percentage of subjects for each adverse events	up to week 128

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Effect to Renal Ultrasound	up to week 128
Effect to Echocardiogram	up to week 128
Serum phosphorus concentration at each test time point	up to week 128
1,25(OH)2D at each test time point	up to week 128
Alkaline phosphatase at each test time point	up to week 128
Urine phosphorus at each test time point	up to week 128
Tubular reabsorption of phosphate at each test time point	up to week 128
TmP/GFR at each test time point	up to week 128
Change from baseline in serum phosphorus	up to week 128
Change from baseline in 1,25(OH)2D	up to week 128
Change from baseline in alkaline phosphatase	up to week 128
Change from baseline in urine phosphorus	up to week 128
Change from baseline in tubular reabsorption of phosphate	up to week 128
Change from baseline in TmP/GFR	up to week 128
Improvement in Radiographic Global Impression of Change(RGI-C) global score	up to week 128
Change from baseline on Rickets Severity Score (RSS) total score	up to week 128
Change from baseline in the Six Minute Walk Test	up to week 128
Change in height-for-age z-scores from baseline	up to week 128
Serum KRN23 concentration	up to week 128
Anti-KRN23 antibody	up to week 128

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): February 17, 2020
• Study Completion (Actual): February 17, 2020

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (Actual): July 28, 2017

Study Record Updates

• Last Update Posted (Actual): September 6, 2022
• Last Update Submitted That Met QC Criteria: August 31, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Metabolism, Inborn Errors; Bone Diseases, Metabolic; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Metal Metabolism, Inborn Errors; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Hypophosphatemia, Familial; Hypophosphatemia; Rickets; Familial Hypophosphatemic Rickets; Rickets, Hypophosphatemic; Osteomalacia
• Other Study ID Numbers: KRN23-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No