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

Primary Purpose

X-linked Hypophosphatemic Rickets/Osteomalacia

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
KRN23
Sponsored by
Kyowa Kirin Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for X-linked Hypophosphatemic Rickets/Osteomalacia

Eligibility Criteria

1 Year - 12 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

KRN23

Arm Description

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

Outcomes

Primary Outcome Measures

Number of subjects for each adverse events
Percentage of subjects for each adverse events

Secondary Outcome Measures

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

Full Information

First Posted
July 11, 2017
Last Updated
August 31, 2022
Sponsor
Kyowa Kirin Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03233126
Brief Title
A Study of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
July 6, 2017 (Actual)
Primary Completion Date
February 17, 2020 (Actual)
Study Completion Date
February 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Kirin Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
X-linked Hypophosphatemic Rickets/Osteomalacia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
KRN23
Arm Type
Experimental
Arm Description
Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 128
Intervention Type
Drug
Intervention Name(s)
KRN23
Intervention Description
Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86
Primary Outcome Measure Information:
Title
Number of subjects for each adverse events
Time Frame
up to week 128
Title
Percentage of subjects for each adverse events
Time Frame
up to week 128
Secondary Outcome Measure Information:
Title
Effect to body temperature
Time Frame
up to week 128
Title
Effect to pulse rate
Time Frame
up to week 128
Title
Effect to respiratory rate
Time Frame
up to week 128
Title
Effect to blood pressure
Time Frame
up to week 128
Title
Effect to 12-Lead Electrocardiogram
Time Frame
up to week 128
Title
Effect to Renal Ultrasound
Time Frame
up to week 128
Title
Effect to Echocardiogram
Time Frame
up to week 128
Title
Serum phosphorus concentration at each test time point
Time Frame
up to week 128
Title
1,25(OH)2D at each test time point
Time Frame
up to week 128
Title
Alkaline phosphatase at each test time point
Time Frame
up to week 128
Title
Urine phosphorus at each test time point
Time Frame
up to week 128
Title
Tubular reabsorption of phosphate at each test time point
Time Frame
up to week 128
Title
TmP/GFR at each test time point
Time Frame
up to week 128
Title
Change from baseline in serum phosphorus
Time Frame
up to week 128
Title
Change from baseline in 1,25(OH)2D
Time Frame
up to week 128
Title
Change from baseline in alkaline phosphatase
Time Frame
up to week 128
Title
Change from baseline in urine phosphorus
Time Frame
up to week 128
Title
Change from baseline in tubular reabsorption of phosphate
Time Frame
up to week 128
Title
Change from baseline in TmP/GFR
Time Frame
up to week 128
Title
Improvement in Radiographic Global Impression of Change(RGI-C) global score
Time Frame
up to week 128
Title
Change from baseline on Rickets Severity Score (RSS) total score
Time Frame
up to week 128
Title
Change from baseline in the Six Minute Walk Test
Time Frame
up to week 128
Title
Change in height-for-age z-scores from baseline
Time Frame
up to week 128
Title
Serum KRN23 concentration
Time Frame
up to week 128
Title
Anti-KRN23 antibody
Time Frame
up to week 128

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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; 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 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 = 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: 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.
Facility Information:
Facility Name
Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center
City
Yokohama
State/Province
Kanagwa
Country
Japan
Facility Name
National University Corporation Osaka University Hospital
City
Suita
State/Province
Osaka
Country
Japan
Facility Name
Osaka Hospital, Japan Community Healthcare Organization (JCHO)
City
Ōsaka
State/Province
Osaka
Country
Japan
Facility Name
Okayama Saiseikai General Hospital Outpatient Center
City
Okayama
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No

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

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