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

JRCT ID: jRCT2080223558

Registered date:15/06/2017

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: X-linked Hypophosphatemic Rickets/Osteomalacia
• Date of first enrollment: 31/07/2017
• Target sample size: 10
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : KRN23
INN of investigational material : burosumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : repeated SC administration

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

Outcome(s)

Primary Outcome

safety
AEs, lab values, vital signs, ECG, renal ultrasound, ECHO

Secondary Outcome

other
-

Key inclusion & exclusion criteria

• Age minimum: >= 1age old
• Age maximum: <= 12age old
• Gender: Both

Include 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 patients at the time of consent
3) Patients who have open growth plate at screening
4) Willing to perform a self-administration of KRN23 by the patients (if appropriate) and legally authorized representative, and available to perform a self-administration by the investigator or subinvestigator, during the study period at the time of consent
5) Diagnosis of XLH, and meeting any of the followings;
a) PHEX mutation in either the patient or in a directly related family member with appropriate X-linked inheritance
b) Serum intact FGF23 level at screening >= 30 pg/mL
6) Finding evidence of rickets (e.g. a cup-shaped depression of the metaphyseal end, enlargement of the epiphyseal line, fuzzing) or clinical symptoms such as X-legs and O-legs, by the judgment of investigator, in the simple X-ray evaluation at screening
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 instructions, as considered by the investigator or subinvestigator

Exclude 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 (e.g., cinacalcet) within 60 days prior to screening
6) Serum calcium levels outside the age-adjusted normal limits
7) Evidence of hyperparathyroidism (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 (implantation or removal), including staples, 8 plates or osteotomy, during the study period
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 HIV antibody, HBs antigen and/or HCV 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) Recieving 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

Related Information

• Primary Sponsor: Kyowa Kirin Co., Ltd.
• Secondary Sponsor: -
• Source(s) of Monetary Support: -
• Secondary ID(s): NCT03233126,JapicCTI-173614