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Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)

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: NCT02312687
Recruitment Status : Completed
First Posted : December 9, 2014
Results First Posted : December 16, 2019
Last Update Posted : December 16, 2019
Sponsor:
Collaborator:
Kyowa Kirin Co., Ltd.
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief Summary:

The primary objectives of this study are to:

  • Assess the long-term safety of KRN23 subcutaneous (SC) administration in adult subjects with XLH
  • Assess the proportion of subjects achieving serum phosphorus levels in the normal range (2.5-4.5 mg/dL) with long-term administration of KRN23
  • Assess long-term pharmacodynamics (PD) of KRN23 as measured by changes in the following: serum intact parathyroid hormone (iPTH); serum and urinary phosphorus; ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) and tubular reabsorption of phosphate (TRP); serum 1,25-dihydroxy vitamin D (1,25[OH]2D); serum fibroblast growth factor 23 (FGF23); bone biomarkers: serum alkaline phosphatase (ALP), bone-specific ALP (BALP), carboxy terminal crosslinked telopeptide of type I collagen (CTx), and procollagen type 1 N-terminal propeptide (P1NP)
  • Assess long-term immunogenicity of KRN23 as measured by presence of anti-KRN23 antibody (ADA)

Condition or disease Intervention/treatment Phase
X-Linked Hypophosphatemia Biological: KRN23 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2b, Open-Label, Long-Term Extension Study to Evaluate the Safety and Pharmacodynamics of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)
Actual Study Start Date : January 30, 2015
Actual Primary Completion Date : November 30, 2018
Actual Study Completion Date : November 30, 2018


Arm Intervention/treatment
Experimental: KRN23
KRN23 subcutaneous (SC) injections every 4 weeks. Starting doses will be based on the subject's last dose in study KRN23-INT-001 (NCT02312687) or KRN23-INT-002 (NCT01571596). Doses may be titrated to achieve the target peak serum phosphorus range.
Biological: KRN23
solution for SC injection
Other Names:
  • burosumab
  • Crysvita®




Primary Outcome Measures :
  1. Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death [ Time Frame: Screening through the end of study plus 4-8 weeks. The mean duration of burosumab exposure was 165.6 weeks (range: 68-184 weeks). ]
    An AE is defined as any untoward medical occurrence, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the investigator or sponsor, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; an important medical event. A TEAE is an AE that occurred on or after the first burosumab dose. AEs were graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). AEs were classified by the Investigator as possibly related, probably related, or definitely related.

  2. Number of Participants With Clinically Significant Changes From Baseline in Vital Signs [ Time Frame: Through Week 184 ]
    Clinically significant changes from baseline reported as adverse events are presented.

  3. Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category [ Time Frame: Through Week 184 ]
    Clinically significant changes from baseline reported as adverse events are presented.

  4. Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category [ Time Frame: Through Week 184 ]
    Clinically significant changes from baseline reported as adverse events are presented.

  5. Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests [ Time Frame: Through Week 184 ]
    Clinically significant changes from baseline reported as adverse events are presented.

  6. Number of Participants With Clinically Significant Changes From Baseline in ECGs [ Time Frame: Through Week 184 ]
    Clinically significant changes from baseline reported as adverse events are presented.

  7. Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category [ Time Frame: Through Week 184 ]
    Clinically significant changes from baseline reported as adverse events are presented.

  8. Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline [ Time Frame: Through Week 184 ]
  9. Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing [ Time Frame: Through Week 184 ]
  10. Change From Baseline Over Time in Serum Phosphorus [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  11. Change From Baseline Over Time in Serum iPTH [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  12. Change From Baseline Over Time in Serum Total FGF23 [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  13. Change From Baseline Over Time in Serum Free FGF23 [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  14. Change From Baseline Over Time in Serum 1,25(OH)2D [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  15. Change From Baseline Ovr Time in 2-hour Urine TmP/GFR [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  16. Change From Baseline Over Time in in 2-hour Urine TRP [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  17. Change From Baseline Over Time in FEP [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  18. Change From Baseline Over Time in 24-hour Urine Phosphorus [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  19. Change From Baseline Over Time in 24-Hour Urine Calcium [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  20. Change From Baseline Over Time in 24-Hour Urine Creatinine [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  21. Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  22. Change From Baseline Over Time in Total ALP [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  23. Change From Baseline Over Time in BALP [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  24. Change From Baseline Over Time in CTx [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]
  25. Change From Baseline Over Time in P1NP [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144 ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Have participated in Kyowa Hakko Kirin Pharma, Inc.'s KRN23-INT-001 (NCT01340482) or KRN23-INT-002 (NCT01571596) studies (received at least 2 doses of KRN23)
  2. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min or eGFR of 45 to < 60 mL/min at Screening with confirmation that the renal insufficiency was not due to nephrocalcinosis.
  3. Sexually active subjects must be willing to use an acceptable method of contraception (e.g., double barrier method) while participating in the study and for 30 days after receiving the last dose of KRN23.

Exclusion Criteria:

  1. Subject experienced a safety-related event in the KRN23-INT-001 or KRN23-INT-002 study that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
  2. Presence of nephrocalcinosis on renal ultrasound that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
  3. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
  4. Participation in an investigational drug or device trial within 30 days of enrollment (other than KRN23-INT-001 or KRN23-INT-002).
  5. Use of a pharmacologic vitamin D metabolite or analog (e.g., calcitriol, doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g., Maalox® and Mylanta®) within 21 days prior to Screening or during the study.
  6. Use of medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening.

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): NCT02312687


Locations
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United States, California
University California San Francisco Hospital
San Francisco, California, United States, 94143
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, Indiana
Indiana University Hospital
Indianapolis, Indiana, United States, 46202
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Texas
Houston Methodist Reasearch Institute
Houston, Texas, United States, 77030
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Kyowa Kirin Co., Ltd.
Investigators
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Study Director: Medical Director Ultragenyx Pharmaceutical Inc
  Study Documents (Full-Text)

Documents provided by Ultragenyx Pharmaceutical Inc:
Study Protocol  [PDF] September 29, 2017
Statistical Analysis Plan  [PDF] April 27, 2016

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Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02312687    
Other Study ID Numbers: UX023-CL203
First Posted: December 9, 2014    Key Record Dates
Results First Posted: December 16, 2019
Last Update Posted: December 16, 2019
Last Verified: November 2019
Keywords provided by Ultragenyx Pharmaceutical Inc:
XLH
FGF23
KRN23
Additional relevant MeSH terms:
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Familial Hypophosphatemic Rickets
Hypophosphatemia
Phosphorus Metabolism Disorders
Metabolic Diseases
Rickets, Hypophosphatemic
Rickets
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Calcium Metabolism Disorders
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders