Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)
- Conditions
- X-Linked Hypophosphatemia
- Interventions
- Biological: KRN23
- Registration Number
- NCT02312687
- Lead Sponsor
- Kyowa Kirin, 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description KRN23 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.
- Primary Outcome Measures
Name Time Method Change From Baseline Over Time in BALP Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in CTx Baseline, Weeks 24, 48, 72, 96, 120, 144 Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category Through Week 184 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 Through Week 184 Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death 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.
Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline Through Week 184 Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Through Week 184 Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests Through Week 184 Clinically significant changes from baseline reported as adverse events are presented.
Number of Participants With Clinically Significant Changes From Baseline in ECGs Through Week 184 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 Through Week 184 Clinically significant changes from baseline reported as adverse events are presented.
Change From Baseline Over Time in 24-hour Urine Phosphorus Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in Serum Phosphorus Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in Serum iPTH Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in Serum Free FGF23 Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in in 2-hour Urine TRP Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in P1NP Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in 24-Hour Urine Calcium Baseline, Weeks 24, 48, 72, 96, 120, 144 Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing Through Week 184 Change From Baseline Over Time in Serum Total FGF23 Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in Serum 1,25(OH)2D Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Ovr Time in 2-hour Urine TmP/GFR Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in 24-Hour Urine Creatinine Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in FEP Baseline, Weeks 24, 48, 72, 96, 120, 144 Change From Baseline Over Time in Total ALP Baseline, Weeks 24, 48, 72, 96, 120, 144
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (5)
Houston Methodist Reasearch Institute
🇺🇸Houston, Texas, United States
Indiana University Hospital
🇺🇸Indianapolis, Indiana, United States
University California San Francisco Hospital
🇺🇸San Francisco, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Duke University
🇺🇸Durham, North Carolina, United States