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

A Phase 3 Long-term Extension Study of KRN23 in Patients With X-linked Hypophosphatemic Rickets/Osteomalacia and a Post-marketing Study of KRN23 Switched From the Phase 3 Long-term Extension Study

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

Study Overview

• Status: Completed
• Conditions: XLH
• Intervention / Treatment: Drug: KRN23

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Okayama, Japan
    • Okayama Saiseikai General Hospital
  • Osaka, Japan
    • Osaka City University Hospital
  • Osaka, Japan
    • Japan Community Health care Organization Osaka Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Hokkaido University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan
      • Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center
  • Osaka
    • Suita, Osaka, Japan
      • National University Corporation Osaka University
  • Tokyo
    • Bunkyō-Ku, Tokyo, Japan
      • The University of Tokyo Hospital
    • Minato-Ku, Tokyo, Japan
      • Toranomon Hospital
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of
      • Seoul National University Hospital
    • Seoul, Korea, Korea, Republic of
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.

2. Patients meeting any of the followings;

   1. For adult XLH patients, completion the final observation at Week 96 in UX023-CL303 or UX023-CL304
   2. For pediatric patients, completion the final observation at Week 64 in UX023-CL301
3. 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
4. For female patient with childbearing potential, or male patients with reproductive capacity; willingness to use acceptable methods of contraception while participating in the study
5. 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

Exclusion Criteria:

1. 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
2. Planned or recommended orthopedic surgery (implantation or removal), including staples, 8 plates or osteotomy, during the study period
3. Blood or blood product transfusion within 60 days prior to scheduled initial administration of investigational drug
4. Use of growth hormone therapy within 12 months prior to scheduled initial administration of investigational drug
5. Use of medication to suppress the secretion of parathyroid hormone (e.g., cinacalcet) within 60 days prior to scheduled initial administration of investigational drug
6. 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
7. Use of a therapeutic monoclonal antibody other than KRN23 within 90 days prior to scheduled initial administration of investigational drug
8. History of being positive for HIV antibody, HBs antigen and/or HCV antibody
9. 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:

1. 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.
2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: KRN23; Subjects will receive subcutaneous injections of KRN23 every 4 weeks (adult) or 2 weeks (pediatric) from Week 0 through Week 140.	Drug: KRN23; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
concentration of Carboxy terminal cross-linked telopeptide of type 1 collagen (CTx) (Adult patients with XLH)		up to week 140
concentration of Procollagen type 1 N-propeptide (P1NP) (Adult patients with XLH)		up to week 140
concentration of Bone-specific alkaline phosphatase (BALP)(Adult patients with XLH)		up to week 140
Concentration of serum alkaline phosphatase (ALP) (Pediatric patients with XLH)		up to week 140
Motor functions (6 minutes walk test (6MWT))		up to week 140
Radiographic findings of fracture and enthesopathy (Adult patients with XLH)	The presence of radiographic fracture and enthesopathy assessed by X-ray (Adult patients with XLH)	up to week 140
Rickets Severity Score (RSS) (Pediatric patients with XLH)		up to week 140
Radiographic Global Impression of Change (RGI-C)(Pediatric patients with XLH)		up to week 140
Z score of height (LMS method) (Pediatric patients with XLH)		up to week 140

Other Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (Serum KRN23 concentration)	up to week 140
Immunogenicity (Anti-KRN23 Antibody)	up to week 140

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 9, 2018
• Primary Completion (ACTUAL): December 4, 2020
• Study Completion (ACTUAL): December 4, 2020

Study Registration Dates

• First Submitted: February 26, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (ACTUAL): March 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 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: KRN23-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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