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

X-Linked Hypophosphatemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02312687
• Other study ID #: UX023-CL203
• Status: Completed
• Phase: Phase 2
• Start date: January 30, 2015
• Est. completion date: November 30, 2018

Study information

• Verified date: November 2019
• Source: Kyowa Kirin, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 30, 2018
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypophosphatemic Rickets
• Hypophosphatemia
• X-Linked Hypophosphatemia

Intervention

Biological:
• KRN23
solution for SC injection

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina
United States	Houston Methodist Reasearch Institute	Houston	Texas
United States	Indiana University Hospital	Indianapolis	Indiana
United States	Yale University School of Medicine	New Haven	Connecticut
United States	University California San Francisco Hospital	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Kyowa Kirin, Inc.	Kyowa Kirin Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Screening through the end of study plus 4-8 weeks. The mean duration of burosumab exposure was 165.6 weeks (range: 68-184 weeks).
Primary	Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	Clinically significant changes from baseline reported as adverse events are presented.	Through Week 184
Primary	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.	Through Week 184
Primary	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.	Through Week 184
Primary	Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests	Clinically significant changes from baseline reported as adverse events are presented.	Through Week 184
Primary	Number of Participants With Clinically Significant Changes From Baseline in ECGs	Clinically significant changes from baseline reported as adverse events are presented.	Through Week 184
Primary	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.	Through Week 184
Primary	Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline		Through Week 184
Primary	Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing		Through Week 184
Primary	Change From Baseline Over Time in Serum Phosphorus		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in Serum iPTH		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in Serum Total FGF23		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in Serum Free FGF23		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in Serum 1,25(OH)2D		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Ovr Time in 2-hour Urine TmP/GFR		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in in 2-hour Urine TRP		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in FEP		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in 24-hour Urine Phosphorus		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in 24-Hour Urine Calcium		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in 24-Hour Urine Creatinine		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in Total ALP		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in BALP		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in CTx		Baseline, Weeks 24, 48, 72, 96, 120, 144
Primary	Change From Baseline Over Time in P1NP		Baseline, Weeks 24, 48, 72, 96, 120, 144