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临床试验/NCT01174446
NCT01174446已完成3 期

Recombinant Factor IX (BAX 326): A Phase 1/3, Prospective, Controlled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety and Immunogenicity in Previously Treated Patients With Severe or Moderately Severe Hemophilia B

Baxalta now part of Shire25 个研究点 分布在 14 个国家目标入组 86 人开始时间: 2010年7月29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
发起方
入组人数
86
试验地点
25
主要终点
Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose
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 purpose of this pivotal Phase 1/3 study is to determine the pharmacokinetic (PK) parameters, the hemostatic efficacy, and the safety of BAX 326, a recombinant factor IX, in previously treated patients (PTPs) with severe and moderately severe hemophilia B.

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
Double (Participant, Investigator)

入排标准

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

入选标准

  • •Main Inclusion Criteria:
  • •Participant is 12 to 65 years old at the time of screening
  • •Participant and/or legal representative has/have provided signed informed consent
  • •Participant has severe (factor IX (FIX) level < 1%) or moderately severe (FIX level 1-2%) hemophilia B (based on the one stage activated partial thromboplastin time (aPTT) assay), as tested at screening at the central laboratory
  • •Participant is previously treated with plasma-derived or recombinant FIX concentrate(s) for a minimum of 150 exposure days (EDs) (based on the participant's medical records); if a verifiable, documented history is unavailable, the participant can be enrolled if s/he has 100-150 EDs to any FIX product that are not fully documented and has participated in Study 050901 for at least 50 EDs to Immunine prior to enrollment (not valid for US and Japan).
  • •Participant has no evidence of a history of FIX inhibitors
  • •If the participant is to receive prophylactic treatment, the participant is willing to receive prophylactic treatment over a period of 6 months.
  • •If the participant is to receive on-demand treatment, the participant has ≥12 documented bleeding episodes requiring treatment within 12 months prior to enrollment and is willing to receive on-demand treatment for the duration of this study.

排除标准

  • •The participant has a history of FIX inhibitors with a titer ≥0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed in the respective local laboratory) at any time prior to screening
  • •The participant has a detectable FIX inhibitor at screening, with a titer ≥0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory
  • •The participant's weight is < 35 kg or > 120 kg
  • •The participant has a history of allergic reaction, eg, anaphylaxis, following exposure to FIX concentrate(s)
  • •The participant has a known hypersensitivity to hamster proteins or recombinant furin (rFurin)
  • •The participant has ongoing or recent evidence of a thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC)

结局指标

主要结局

Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose

时间窗: 72 hours

Computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2.

次要结局

  • Study Parts 1 and 3: Clearance (CL)(0-30 minutes before infusion up to 72 hours post-infusion)
  • Study Parts 1 and 3: Volume of Distribution at Steady State (Vss)(0-30 minutes before infusion up to 72 hours post-infusion)
  • Study Parts 1 and 3: Mean Residence Time (MRT)(0-30 minutes before infusion up to 72 hours post-infusion)
  • Incremental Recovery (IR) at 30 Minutes Over Time(0-30 minutes before infusion and 30 minutes post-infusion)
  • Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326(Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks))
  • Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose)(0-30 minutes before infusion up to 72 hours post-infusion)
  • Consumption of BAX326 Per Participant: Median Number of Infusions Per Month(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks))
  • Number of Participants Who Experienced Thrombotic Events(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • SF-36: HRQoL Physical Functioning' (PF)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Change in Incremental Recovery (IR) at 30 Minutes Over Time(0-30 minutes before infusion and 30 minutes post-infusion)
  • Consumption of BAX326 Per Event Per Participant(Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks))
  • Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks))
  • Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)(0-30 minutes before infusion up to 1 hour post-infusion)
  • Study Parts 1 and 3: Half Life (T 1/2)(0-30 minutes before infusion up to 72 hours post-infusion)
  • Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause(Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5))
  • Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause(At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3))
  • Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause(Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks))
  • Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability)(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Health Resource Use - Number of Hospitalizations(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Health Resource Use - Days Lost From Work or School(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Occurrence of Treatment Related Total Binding Antibodies(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Number of Adverse Events (AEs) After BAX326 Treatment(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks))
  • EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • SF-36: HRQoL 'Mental Health' (MH)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • SF-36: HRQoL Role-Physical (RP)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • SF-36: HRQoL Role-Emotional(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Number of Participants With Adverse Events (AEs) After BAX326 Treatment(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks))
  • General Pain Assessment Through a Visual Analog Scale (VAS)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • SF-36: HRQoL Bodily Pain(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Health Resource Use - Unscheduled Doctor's Office Visits(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • SF-36: HRQoL Vitality(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • SF-36: HRQoL General Health(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Health Resource Use - Total Days of Hospital Stay(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • Health Resource Use - Emergency Room Visits(Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks))
  • SF-36: HRQoL Mental Health(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • SF-36: HRQoL Social Functioning(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))
  • Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)(Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31))

研究者

发起方
Baxalta now part of Shire
申办方类型
Industry
责任方
Sponsor

研究点 (25)

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