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

• ClinicalTrials.gov Identifier: NCT04308096
• Recruitment Status: Completed
• First Posted: March 13, 2020
• Last Update Posted: September 6, 2022
• Sponsor: Kyowa Kirin Co., Ltd.
• Information provided by (Responsible Party): Kyowa Kirin Co., Ltd.

Study Description

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

Condition or disease	Intervention/treatment	Phase
XLH	Drug: KRN23	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 9, 2018
• Actual Primary Completion Date: December 4, 2020
• Actual Study Completion Date: December 4, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of subjects for each adverse events [ Time Frame: up to week 140 ]
2. Effect to Body temperature [ Time Frame: up to week 140 ]
3. Effect to Pulse rate [ Time Frame: up to week 140 ]
4. Effect to Respiratory rate [ Time Frame: up to week 140 ]
5. Effect to Systolic blood pressure in sitting position [ Time Frame: up to week 140 ]
6. Effect to Diastolic blood pressure in sitting position [ Time Frame: up to week 140 ]
7. Effect to 12-lead electrocardiogram (ECG) [ Time Frame: up to week 140 ]
   The presence of abnormality in the electrocardiogram
8. Effect to renal ultrasound [ Time Frame: up to week 140 ]
   The evaluation to nephrocalcinosis in five grades by renal ultrasound
9. Effect to Echocardiogram [ Time Frame: up to week 140 ]
   The presence of ectopic calcification in the heart by Echocardiogram

Secondary Outcome Measures :

1. Concentration of serum phosphorus [ Time Frame: up to week 140 ]
2. Concentration of serum 1,25(OH)2D [ Time Frame: up to week 140 ]
3. Concentration of urinary phosphorus [ Time Frame: up to week 140 ]
4. Concentration of tubular resorption of phosphorus（TRP） [ Time Frame: up to week 140 ]
5. Concentration of maximum tubular reabsorption of phosphate/glomerular filtration rate (TmP/GFR) [ Time Frame: up to week 140 ]
6. concentration of Carboxy terminal cross-linked telopeptide of type 1 collagen (CTx) (Adult patients with XLH) [ Time Frame: up to week 140 ]
7. concentration of Procollagen type 1 N-propeptide (P1NP) (Adult patients with XLH) [ Time Frame: up to week 140 ]
8. concentration of Bone-specific alkaline phosphatase (BALP)(Adult patients with XLH) [ Time Frame: up to week 140 ]
9. Concentration of serum alkaline phosphatase (ALP) (Pediatric patients with XLH) [ Time Frame: up to week 140 ]
10. Motor functions (6 minutes walk test (6MWT)) [ Time Frame: up to week 140 ]
11. Radiographic findings of fracture and enthesopathy (Adult patients with XLH) [ Time Frame: up to week 140 ]
    The presence of radiographic fracture and enthesopathy assessed by X-ray (Adult patients with XLH)
12. Rickets Severity Score (RSS) (Pediatric patients with XLH) [ Time Frame: up to week 140 ]
13. Radiographic Global Impression of Change (RGI-C)(Pediatric patients with XLH) [ Time Frame: up to week 140 ]
14. Z score of height (LMS method) (Pediatric patients with XLH) [ Time Frame: up to week 140 ]

Other Outcome Measures:

1. Pharmacokinetics (Serum KRN23 concentration) [ Time Frame: up to week 140 ]
2. Immunogenicity (Anti-KRN23 Antibody) [ Time Frame: up to week 140 ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Japan

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center

Yokohama, Kanagawa, Japan

National University Corporation Osaka University

Suita, Osaka, Japan

The University of Tokyo Hospital

Bunkyō-Ku, Tokyo, Japan

Toranomon Hospital

Minato-Ku, Tokyo, Japan

Okayama Saiseikai General Hospital

Okayama, Japan

Japan Community Health Care Organization Osaka Hospital

Osaka, Japan

Osaka City University Hospital

Osaka, Japan

Korea, Republic of

Asan Medical Center

Seoul, Korea, Korea, Republic of

Seoul National University hospital

Seoul, Korea, Korea, Republic of

Sponsors and Collaborators

Kyowa Kirin Co., Ltd.

More Information

• Responsible Party: Kyowa Kirin Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04308096
• Other Study ID Numbers: KRN23-004
• First Posted: March 13, 2020
• Last Update Posted: September 6, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Familial Hypophosphatemic Rickets; Rickets; Osteomalacia; Rickets, Hypophosphatemic; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Hypophosphatemia; Phosphorus Metabolism Disorders; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn