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

X-linked Hypophosphatemic Rickets/Osteomalacia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03233126
• Other study ID #: KRN23-003
• Status: Completed
• Phase: Phase 3
• Start date: July 6, 2017
• Est. completion date: February 17, 2020

Study information

• Verified date: August 2022
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 17, 2020
• Est. primary completion date: February 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypophosphatemic Rickets
• Osteomalacia
• Rickets
• X-linked Hypophosphatemic Rickets/Osteomalacia

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Kyowa Kirin Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects for each adverse events		up to week 128
Primary	Percentage of subjects for each adverse events		up to week 128
Secondary	Effect to body temperature		up to week 128
Secondary	Effect to pulse rate		up to week 128
Secondary	Effect to respiratory rate		up to week 128
Secondary	Effect to blood pressure		up to week 128
Secondary	Effect to 12-Lead Electrocardiogram		up to week 128
Secondary	Effect to Renal Ultrasound		up to week 128
Secondary	Effect to Echocardiogram		up to week 128
Secondary	Serum phosphorus concentration at each test time point		up to week 128
Secondary	1,25(OH)2D at each test time point		up to week 128
Secondary	Alkaline phosphatase at each test time point		up to week 128
Secondary	Urine phosphorus at each test time point		up to week 128
Secondary	Tubular reabsorption of phosphate at each test time point		up to week 128
Secondary	TmP/GFR at each test time point		up to week 128
Secondary	Change from baseline in serum phosphorus		up to week 128
Secondary	Change from baseline in 1,25(OH)2D		up to week 128
Secondary	Change from baseline in alkaline phosphatase		up to week 128
Secondary	Change from baseline in urine phosphorus		up to week 128
Secondary	Change from baseline in tubular reabsorption of phosphate		up to week 128
Secondary	Change from baseline in TmP/GFR		up to week 128
Secondary	Improvement in Radiographic Global Impression of Change(RGI-C) global score		up to week 128
Secondary	Change from baseline on Rickets Severity Score (RSS) total score		up to week 128
Secondary	Change from baseline in the Six Minute Walk Test		up to week 128
Secondary	Change in height-for-age z-scores from baseline		up to week 128
Secondary	Serum KRN23 concentration		up to week 128
Secondary	Anti-KRN23 antibody		up to week 128