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

NCT04308096 | Completed Phase 3

• 1 other identifier: KRN23-004
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 10

Brief Summary

Before switching to the post-marketing study: Assess the efficacy and safety of KRN23 administered subcutaneously once every 4 or 2 weeks in adult or children with XLH After switching to the post-marketing study: To evaluate the safety and efficacy of KRN23, which was switched from the investigational product to the post-marketing investigational product, at the approved dose and dosing regimen in subjects who continued treatment

Conditions

XLH

Outcome Measures

Primary Outcomes (9)

• Number of subjects for each adverse events

  up to week 140

• Effect to Body temperature

  up to week 140

• Effect to Pulse rate

  up to week 140

• Effect to Respiratory rate

  up to week 140

• Effect to Systolic blood pressure in sitting position

  up to week 140

• Effect to Diastolic blood pressure in sitting position

  up to week 140

• Effect to 12-lead electrocardiogram (ECG)

  The presence of abnormality in the electrocardiogram

  up to week 140

• Effect to renal ultrasound

  The evaluation to nephrocalcinosis in five grades by renal ultrasound

  up to week 140

• Effect to Echocardiogram

  The presence of ectopic calcification in the heart by Echocardiogram

  up to week 140

Secondary Outcomes (14)

• Concentration of serum phosphorus

  up to week 140

• Concentration of serum 1,25(OH)2D

  up to week 140

• Concentration of urinary phosphorus

  up to week 140

• Concentration of tubular resorption of phosphorus（TRP）

  up to week 140

• Concentration of maximum tubular reabsorption of phosphate/glomerular filtration rate (TmP/GFR)

  up to week 140

Other Outcomes (2)

• Pharmacokinetics (Serum KRN23 concentration)

  up to week 140

• Immunogenicity (Anti-KRN23 Antibody)

  up to week 140

Study Arms (1)

KRN23

EXPERIMENTAL

Subjects will receive subcutaneous injections of KRN23 every 4 weeks (adult) or 2 weeks (pediatric) from Week 0 through Week 140.

Drug: KRN23

Interventions

KRN23 DRUG

The starting dose of KRN23 will be the dose used for the last administration in the preceding studies. The dose may be modified subsequently in accordance with the criteria for dose and dose adjustment.

KRN23

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Personally submitted voluntary written informed consent to participate in the study; For pediatric patients, 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.
• Patients meeting any of the followings;
• For adult XLH patients, completion the final observation at Week 96 in UX023-CL303 or UX023-CL304
• For pediatric patients, completion the final observation at Week 64 in UX023-CL301
• For female patients; women of childbearing potential (except for females who have not reached menarche, permanently sterilized, postmenopausal \[12 months with no menses without an alternative medical cause\] or anatomically not of childbearing potential) with negative pregnancy test at pre-treatment assessment of Week 0
• For female patient with childbearing potential, or male patients with reproductive capacity; willingness to use acceptable methods of contraception while participating in the study
• Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by investigator or subinvestigator

You may not qualify if:

• Use of oral phosphate for treating XLH, pharmacologic vitamin D metabolites or analogs, aluminum hydroxide antacids, systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to scheduled initial administration of investigational drug
• Planned or recommended orthopedic surgery (implantation or removal), including staples, 8 plates or osteotomy, during the study period
• Blood or blood product transfusion within 60 days prior to scheduled initial administration of investigational drug
• Use of growth hormone therapy within 12 months prior to scheduled initial administration of investigational drug
• Use of medication to suppress the secretion of parathyroid hormone (e.g., cinacalcet) within 60 days prior to scheduled initial administration of investigational drug
• Use of any investigational product (except for investigational product of the preceding study) or investigational medical device within 4 months prior to scheduled initial administration of investigational drug, or requirement for any investigational agent prior to completion of all scheduled study assessments
• Use of a therapeutic monoclonal antibody other than KRN23 within 90 days prior to scheduled initial administration of investigational drug
• History of being positive for HIV antibody, HBs antigen and/or HCV antibody
• Anyone otherwise considered unsuitable for the study by the investigator or subinvestigator
• At the time of switching to the post-marketing clinical study:
• Subjects eligible for enrollment in the post-marketing clinical study must have met both of the following criteria:
• Personally submitted voluntary written informed consent to participate in the postmarketing clinical study. For pediatric patients, personally submitted voluntary written informed consent by a legally authorized representative. If appropriate, written or verbal assent to participate in the post-marketing clinical study was to be obtained from subjects.
• Switching to the post-marketing clinical study was necessary and appropriate for the subject from the viewpoint of efficacy and safety, as judged by the investigator or subinvestigator

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead

Study Sites (10)

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Location

Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center

Yokohama, Kanagawa, Japan

Location

National University Corporation Osaka University

Suita, Osaka, Japan

Location

The University of Tokyo Hospital

Bunkyō-Ku, Tokyo, Japan

Location

Toranomon Hospital

Minato-Ku, Tokyo, Japan

Location

Okayama Saiseikai General Hospital

Okayama, Japan

Location

Japan Community Health Care Organization Osaka Hospital

Osaka, Japan

Location

Osaka City University Hospital

Osaka, Japan

Location

Asan Medical Center

Seoul, Korea, South Korea

Location

Seoul National University hospital

Seoul, Korea, South Korea

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

Interventions

burosumab

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: February 26, 2020
• First Posted: March 13, 2020
• Study Start: January 9, 2018
• Primary Completion: December 4, 2020
• Study Completion: December 4, 2020
• Last Updated: September 6, 2022

Record last verified: 2022-09

Locations

JP (8); KR (2)