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临床试验/NCT02526160
NCT02526160已完成3 期

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study With Open-Label Extension to Assess the Efficacy and Safety of KRN23 in Adults With X-linked Hypophosphatemia (XLH)

Kyowa Kirin, Inc.50 个研究点 分布在 8 个国家目标入组 134 人开始时间: 2015年10月22日最近更新:
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适应症

试验速览

阶段
3 期
状态
已完成
入组人数
134
试验地点
50
主要终点
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
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 efficacy objective of this study is to establish the effect of burosumab treatment compared with placebo on increasing serum phosphorus levels in adults with XLH.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Treatment
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 65 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Male or female, aged 18 - 65 years, inclusive
  • •Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs) and at least ONE of the following at Screening:
  • •Documented phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) mutation in the patient or a directly related family member with appropriate X-linked inheritance
  • •Serum intact FGF23 (iFGF23) level > 30 pg/mL by Kainos assay
  • •Biochemical findings consistent with XLH at Screening Visit 2 following overnight fasting (min. 8 hours):
  • •Serum phosphorus < 2.5 mg/dL
  • •TmP/GFR of < 2.5 mg/dL
  • •Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥ 4 on Brief Pain Inventory (BPI) Questions 3 (Worst Pain) at Screening Visit
  • •(Skeletal pain that, in the opinion of the investigator, is attributed solely to causes other than XLH/osteomalacia-for example, back or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location-in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
  • •Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) or eGFR of 45 60 mL/min at Screening Visit 2 with confirmation that the renal insufficiency is not due to nephrocalcinosis
  • •If taking chronic pain medications (including narcotic pain medications/opioids), must be on a stable regimen for at least 21 days prior to Screening Visit 1, and be willing to maintain medications at the same stable dose(s) and schedule throughout the Placebo-controlled Treatment Period of the study. The dose must not exceed 60 mg oral morphine equivalents/day
  • •Provide written informed consent or if a minor, provide written consent and have a legally authorized representative willing and able to provide written informed consent, after the nature of the study has been explained, and prior to any research-related procedures
  • •Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
  • •Females of child-bearing potential must have a negative urine pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not to be of childbearing potential include those who have been in menopause for at least two years prior to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total hysterectomy or bilateral salpingo-oophorectomy
  • •Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use an effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence) from the period following the signing of the informed consent through 12 weeks after last dose of study drug
  • •Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments
  • •Must have completed at least 4 of 7 days of the patient diaries before the Baseline visit.

排除标准

  • •Use of a pharmacologic vitamin D metabolite or analog (calcitriol, doxercalciferol, and paricalcitol) within 14 days prior to Screening Visit 2
  • •Use of oral phosphate within 14 days prior to Screening Visit 2
  • •Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening Visit 2
  • •Chronic use of systemic corticosteroids defined as more than 10 days in the previous 2 months
  • •Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening Visit 2
  • •Serum intact parathyroid hormone (iPTH) ≥ 2.5 upper limit of normal (ULN) at Screening Visit 1
  • •Use of medication to suppress parathyroid hormone (PTH) (cinacalcet for example) within 60 days prior to Screening Visit 1
  • •Use of oral bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1
  • •Use of denosumab in the 6 months prior to Screening Visit 1
  • •Use of teriparatide in the 2 months prior to Screening Visit 1
  • •Planned or recommended orthopedic surgery within the first 24 weeks of the clinical trial period
  • •History of traumatic fracture or orthopedic surgery within 6 months prior to Screening Visit 1
  • •Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to Screening Visit 1
  • •Use of any investigational product or investigational medical device within 30 days prior to Screening Visit 1, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  • •OR, in Japan, use of any investigational product or investigational medical device within 4 months prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  • •Pregnant or breastfeeding at Screening /Baseline or planning to become pregnant (self or partner) at any time during the study
  • •Unable or unwilling to withhold prohibited medications throughout the study
  • •Presence or history of any hypersensitivity, allergic or anaphylactic reactions to any monoclonal antibody or KRN23 excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects.
  • •Prior history of positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
  • •History of recurrent infection or predisposition to infection, or of known immunodeficiency
  • •Presence of malignant neoplasm (except basal cell carcinoma)
  • •Presence of a concurrent disease or condition that would interfere with study participation or affect safety
  • •Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study

结局指标

主要结局

Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24

时间窗: Baseline through Week 24

次要结局

  • Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score(Baseline, 24 weeks)
  • Change From Baseline to Week 24 in the WOMAC Physical Function Score(Baseline, 24 weeks)
  • Change From Baseline Over Time in BPI Worst Pain Score(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in BFI Global Fatigue Score(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in WOMAC Physical Function Score(Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144)
  • Percent Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24(Baseline through Week 24)
  • Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score(Baseline, 24 weeks)
  • Change From Baseline Over Time in BFI Worst Fatigue Score(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx)(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in Serum Phosphorus(Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144)
  • Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus(Baseline, Week 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)(Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96)
  • Change From Baseline Over Time in BPI Pain Interference Score(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in WOMAC Stiffness Score(Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144)
  • Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Percent Change From Baseline Over Time in Serum Phosphorus(Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144)
  • Percent Change From Baseline Over Time in TmP/GFR(Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96)
  • Percent Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24(Baseline through Week 24)
  • Change From Baseline Over Time in BPI Pain Severity Score(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP)(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in 24-Hour Urinary Phosphorus(Baseline, Week 12, 24, 36, 48, 72, 96)
  • Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24(Baseline through Week 24)
  • Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24(Baseline through Week 24)
  • Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24(Baseline through Week 24)
  • Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP)(Baseline, Weeks 12, 24, 36, 48, 72, 96)
  • Change From Baseline Over Time in Serum 1,25(OH)2D(Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144)
  • Percent Change From Baseline Over Time in Serum 1,25(OH)2D(Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144)
  • Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP)(Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96)
  • Percent Change From Baseline Over Time in TRP(Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96)
  • Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24(Baseline through Week 24)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (50)

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