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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03233126
Recruitment Status : Active, not recruiting
First Posted : July 28, 2017
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Kyowa Kirin Co., Ltd.

Brief Summary:
The purpose of the study is to assess the efficacy and safety of KRN23 administered subcutaneously once every 2 weeks in children with X-linked hypophosphatemic rickets/osteomalacia(XLH)

Condition or disease Intervention/treatment Phase
X-linked Hypophosphatemic Rickets/Osteomalacia Drug: KRN23 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia
Actual Study Start Date : July 6, 2017
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : March 2020


Arm Intervention/treatment
Experimental: KRN23 Drug: KRN23
Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86




Primary Outcome Measures :
  1. Number of subjects for each adverse events [ Time Frame: up to week 88 ]
  2. Percentage of subjects for each adverse events [ Time Frame: up to week 88 ]

Secondary Outcome Measures :
  1. Effect to pulse rate [ Time Frame: up to week 88 ]
  2. Effect to respiratory rate [ Time Frame: up to week 88 ]
  3. Effect to blood pressure [ Time Frame: up to week 88 ]
  4. Effect to 12-Lead Electrocardiogram [ Time Frame: up to week 88 ]
  5. Effect to Renal Ultrasound [ Time Frame: up to week 88 ]
  6. Effect to Echocardiogram [ Time Frame: up to week 88 ]
  7. Serum phosphorus concentration at each test time point [ Time Frame: up to week 88 ]
  8. 1,25(OH)2D at each test time point [ Time Frame: up to week 88 ]
  9. Alkaline phosphatase at each test time point [ Time Frame: up to week 88 ]
  10. Urine phosphorus at each test time point [ Time Frame: up to week 88 ]
  11. Tubular reabsorption of phosphate at each test time point [ Time Frame: up to week 88 ]
  12. TmP/GFR at each test time point [ Time Frame: up to week 88 ]
  13. Change from baseline in serum phosphorus [ Time Frame: up to week 88 ]
  14. Change from baseline in 1,25(OH)2D [ Time Frame: up to week 88 ]
  15. Change from baseline in alkaline phosphatase [ Time Frame: up to week 88 ]
  16. Change from baseline in urine phosphorus [ Time Frame: up to week 88 ]
  17. Change from baseline in tubular reabsorption of phosphate [ Time Frame: up to week 88 ]
  18. Change from baseline in TmP/GFR [ Time Frame: up to week 88 ]
  19. Improvement in Radiographic Global Impression of Change(RGI-C) global score [ Time Frame: up to week 88 ]
  20. Change from baseline on Rickets Severity Score (RSS) total score [ Time Frame: up to week 88 ]
  21. Change from baseline in the Six Minute Walk Test [ Time Frame: up to week 88 ]
  22. Change in height-for-age z-scores from baseline [ Time Frame: up to week 88 ]
  23. Profiles of maximum concentration (Cmax) [ Time Frame: up to week 88 ]
  24. Profiles of half-life (t1/2) [ Time Frame: up to week 88 ]
  25. Profiles of area under the curve (AUC) [ Time Frame: up to week 88 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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
  3. Patients who have open growth plate
  4. Willing to perform a self-administration of KRN23 and available to perform a self-administration
  5. Diagnosis of XLH, and meeting any of the followings;

    1. phosphate-regulating gene with homologies to endopeptidases on the X chromosome(PHEX) mutation in either the patient or in a directly related family member with appropriate X-linked inheritance
    2. Serum intact FGF23 level at screening ≥ 30 pg/mL
  6. Finding evidence of rickets or clinical symptoms
  7. Meeting all of following criteria for laboratory test related to XLH;

    1. Serum P: < 3.0 mg/dL
    2. Serum Cr: Within the age-adjusted normal limits
    3. 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's instructions, as considered by the investigator or subinvestigator

Exclusion 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 within 60 days prior to screening
  6. Serum calcium levels outside the age-adjusted normal limits
  7. Intact parathyroid hormone(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
  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 human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus 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. Receiving 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03233126


Locations
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Japan
Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center
Yokohama, Kanagwa, Japan
National University Corporation Osaka University Hospital
Suita, Osaka, Japan
Osaka Hospital, Japan Community Healthcare Organization (JCHO)
Ōsaka, Osaka, Japan
Okayama Saiseikai General Hospital Outpatient Center
Okayama, Japan
Sponsors and Collaborators
Kyowa Kirin Co., Ltd.

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Responsible Party: Kyowa Kirin Co., Ltd.
ClinicalTrials.gov Identifier: NCT03233126     History of Changes
Other Study ID Numbers: KRN23-003
First Posted: July 28, 2017    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Rickets
Osteomalacia
Rickets, Hypophosphatemic
Familial Hypophosphatemic Rickets
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
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn