Clinical trial NCT02312687: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: X-Linked Hypophosphatemia
Keywords: XLH
FGF23
KRN23
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Kirin Co., Ltd.
First posted: 2014-12-09
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death
timeFrame: Screening through the end of study plus 4-8 weeks. The mean duration of burosumab exposure was 165.6 weeks (range: 68-184 weeks).
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
timeFrame: Through Week 184
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category
timeFrame: Through Week 184
measure: Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category
timeFrame: Through Week 184
measure: Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests
timeFrame: Through Week 184
measure: Number of Participants With Clinically Significant Changes From Baseline in ECGs
timeFrame: Through Week 184
measure: Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category
timeFrame: Through Week 184
measure: Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline
timeFrame: Through Week 184
measure: Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing
timeFrame: Through Week 184
measure: Change From Baseline Over Time in Serum Phosphorus
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in Serum iPTH
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in Serum Total FGF23
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in Serum Free FGF23
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in Serum 1,25(OH)2D
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Ovr Time in 2-hour Urine TmP/GFR
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in in 2-hour Urine TRP
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in FEP
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in 24-hour Urine Phosphorus
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in 24-Hour Urine Calcium
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in 24-Hour Urine Creatinine
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in Total ALP
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in BALP
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in CTx
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
measure: Change From Baseline Over Time in P1NP
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University California San Francisco Hospital
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Houston
country: United States
facility: Houston Methodist Reasearch Institute
state: Texas
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Medical Director
role: STUDY_DIRECTOR
References: