Back to resultsLong-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)
Primary Purpose
X-Linked Hypophosphatemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
KRN23
Sponsored by
About this trial
This is an interventional treatment trial for X-Linked Hypophosphatemia focused on measuring XLH, FGF23, KRN23
Eligibility Criteria
Inclusion Criteria:
- 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)
- 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.
- 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:
- 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.
- Presence of nephrocalcinosis on renal ultrasound that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
- Participation in an investigational drug or device trial within 30 days of enrollment (other than KRN23-INT-001 or KRN23-INT-002).
- 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.
- Use of medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening.
Sites / Locations
- University California San Francisco Hospital
- Yale University School of Medicine
- Indiana University Hospital
- Duke University
- Houston Methodist Reasearch Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
KRN23
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death
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.
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category
Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category
Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests
Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Clinically Significant Changes From Baseline in ECGs
Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category
Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline
Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing
Change From Baseline Over Time in Serum Phosphorus
Change From Baseline Over Time in Serum iPTH
Change From Baseline Over Time in Serum Total FGF23
Change From Baseline Over Time in Serum Free FGF23
Change From Baseline Over Time in Serum 1,25(OH)2D
Change From Baseline Ovr Time in 2-hour Urine TmP/GFR
Change From Baseline Over Time in in 2-hour Urine TRP
Change From Baseline Over Time in FEP
Change From Baseline Over Time in 24-hour Urine Phosphorus
Change From Baseline Over Time in 24-Hour Urine Calcium
Change From Baseline Over Time in 24-Hour Urine Creatinine
Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio
Change From Baseline Over Time in Total ALP
Change From Baseline Over Time in BALP
Change From Baseline Over Time in CTx
Change From Baseline Over Time in P1NP
Secondary Outcome Measures
Full Information
NCT ID
NCT02312687
First Posted
December 3, 2014
Last Updated
April 14, 2023
Sponsor
Kyowa Kirin, Inc.
Collaborators
Kyowa Kirin Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02312687
Brief Title
Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
January 30, 2015 (Actual)
Primary Completion Date
November 30, 2018 (Actual)
Study Completion Date
November 30, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Kirin, Inc.
Collaborators
Kyowa Kirin Co., Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
X-Linked Hypophosphatemia
Keywords
XLH, FGF23, KRN23
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
KRN23
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
KRN23
Other Intervention Name(s)
burosumab, Crysvita®
Intervention Description
solution for SC injection
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death
Description
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.
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).
Title
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Description
Clinically significant changes from baseline reported as adverse events are presented.
Time Frame
Through Week 184
Title
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category
Description
Clinically significant changes from baseline reported as adverse events are presented.
Time Frame
Through Week 184
Title
Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category
Description
Clinically significant changes from baseline reported as adverse events are presented.
Time Frame
Through Week 184
Title
Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests
Description
Clinically significant changes from baseline reported as adverse events are presented.
Time Frame
Through Week 184
Title
Number of Participants With Clinically Significant Changes From Baseline in ECGs
Description
Clinically significant changes from baseline reported as adverse events are presented.
Time Frame
Through Week 184
Title
Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category
Description
Clinically significant changes from baseline reported as adverse events are presented.
Time Frame
Through Week 184
Title
Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline
Time Frame
Through Week 184
Title
Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing
Time Frame
Through Week 184
Title
Change From Baseline Over Time in Serum Phosphorus
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in Serum iPTH
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in Serum Total FGF23
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in Serum Free FGF23
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in Serum 1,25(OH)2D
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Ovr Time in 2-hour Urine TmP/GFR
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in in 2-hour Urine TRP
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in FEP
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in 24-hour Urine Phosphorus
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in 24-Hour Urine Calcium
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in 24-Hour Urine Creatinine
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in Total ALP
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in BALP
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in CTx
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
Title
Change From Baseline Over Time in P1NP
Time Frame
Baseline, Weeks 24, 48, 72, 96, 120, 144
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
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.
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:
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.
Presence of nephrocalcinosis on renal ultrasound that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
Participation in an investigational drug or device trial within 30 days of enrollment (other than KRN23-INT-001 or KRN23-INT-002).
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.
Use of medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
University California San Francisco Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Indiana University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Houston Methodist Reasearch Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)
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