A Study of KRN23 in Adult and Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia
Study Details
Study Description
Brief Summary
Assess the efficacy and safety of KRN23 administered subcutaneously once every 4 or 2 weeks in adult or children with XLH
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: KRN23 Subjects will receive subcutaneous injections of KRN23 every 4 weeks (adult) 2 weeks (pediatric) |
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
- Number of subjects for each adverse events [up to 72 weeks]
- Body temperature [up to 72 weeks]
- Pulse rate [up to 72 weeks]
- Respiratory rate [up to 72 weeks]
- Systolic blood pressure in sitting position [up to 72 weeks]
- Diastolic blood pressure in sitting position [up to 72 weeks]
- Effect to 12-lead electrocardiogram (ECG) [up to 72 weeks]
The presence of abnormality in the electrocardiogram
- Effect to renal ultrasound [up to 72 weeks]
The evaluation to nephrocalcinosis in five grades by renal ultrasound
- Effect to Echocardiogram [up to 72 weeks]
The presence of ectopic calcification in the heart by Echocardiogram
Secondary Outcome Measures
- Concentration of serum phosphorus [up to 72 weeks]
- Concentration of serum 1,25(OH)2D [up to 72 weeks]
- Concentration of urinary phosphorus [up to 72 weeks]
- Tubular reabsorption of phosphate from 2-hour urine [up to 72 weeks]
- Concentration of maximum tubular reabsorption of phosphate/glomerular filtration rate (TmP/GFR) [up to 72 weeks]
- Carboxy terminal cross-linked telopeptide of type 1 collagen (CTx) [up to 72 weeks]
- Procollagen type 1 N-propeptide (P1NP) [up to 72 weeks]
- Bone-specific alkaline phosphatase (BALP) [up to 72 weeks]
- Concentration of serum alkaline phosphatase (ALP) (Pediatric patients with XLH) [up to 72 weeks]
- Motor functions (6 minutes walk test (6MWT)) [up to 72 weeks]
- Radiographic findings of fracture and enthesopathy (Adult patients with XLH) [up to 72 weeks]
The presence of radiographic fracture and enthesopathy assessed by X-ray (Adult patients with XLH)
- Rickets Severity Score (RSS) [up to 72 weeks]
- Radiographic Global Impression of Change (RGI-C) [up to 72 weeks]
- Z score of height (LMS method) (Pediatric patients with XLH) [up to 72 weeks]
Other Outcome Measures
- Pharmacokinetics (Serum KRN23 concentration) [up to 72 weeks]
- Immunogenicity (Anti-KRN23 Antibody) [up to 72 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
- 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.
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Patients meeting any of the followings;
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For adult XLH patients, completion the final observation at Week 96 in UX023-CL303 or UX023-CL304
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For pediatric patients, completion the final observation at Week 64 in UX023-CL301
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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
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For female patient with childbearing potential, or male patients with reproductive capacity; willingness to use acceptable methods of contraception while participating in the study
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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:
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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
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Planned or recommended orthopedic surgery (implantation or removal), including staples, 8 plates or osteotomy, during the study period
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Blood or blood product transfusion within 60 days prior to scheduled initial administration of investigational drug
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Use of growth hormone therapy within 12 months prior to scheduled initial administration of investigational drug
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Use of medication to suppress the secretion of parathyroid hormone (e.g., cinacalcet) within 60 days prior to scheduled initial administration of investigational drug
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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
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Use of a therapeutic monoclonal antibody other than KRN23 within 90 days prior to scheduled initial administration of investigational drug
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History of being positive for HIV antibody, HBs antigen and/or HCV antibody
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Anyone otherwise considered unsuitable for the study by the investigator or subinvestigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hokkaido University Hospital | Sapporo | Hokkaido | Japan | |
| 2 | Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center | Yokohama | Kanagawa | Japan | |
| 3 | National University Corporation Osaka University | Suita | Osaka | Japan | |
| 4 | The University of Tokyo Hospital | Bunkyō-Ku | Tokyo | Japan | |
| 5 | Toranomon Hospital | Minato-Ku | Tokyo | Japan | |
| 6 | Okayama Saiseikai General Hospital | Okayama | Japan | ||
| 7 | Japan Community Health Care Organization Osaka Hospital | Osaka | Japan | ||
| 8 | Osaka City University Hospital | Osaka | Japan | ||
| 9 | Asan Medical Center | Seoul | Korea | Korea, Republic of | |
| 10 | Seoul National University hospital | Seoul | Korea | Korea, Republic of |
Sponsors and Collaborators
- Kyowa Kirin Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KRN23-004