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)

Kyowa Kirin, Inc.10 个研究点分布在 1 个国家目标入组 20 人开始时间: 2015年1月30日最近更新: 2024年5月6日

适应症

试验速览

阶段: 2 期
状态: 已完成
发起方: Kyowa Kirin, Inc.
入组人数: 20
试验地点: 10
主要终点: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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)

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

性别: All
接受健康志愿者: 否

入选标准

•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.

排除标准

•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.

结局指标

主要结局

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: Through Week 184

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: Through Week 184

Clinically significant changes from baseline reported as adverse events are presented.

Change From Baseline Over Time in in 2-hour Urine TRP