NCT01913405已完成3 期
A Phase 3, Multi-Center, Open Label Study of Efficacy and Safety of PEGylated rFVIII (BAX 855) in Previously Treated Patients With Severe Hemophilia A Undergoing Surgical or Other Invasive Procedures
Baxalta now part of Shire44 个研究点 分布在 9 个国家目标入组 30 人开始时间: 2013年12月20日最近更新:
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 44
- 主要终点
- Global Hemostatic Efficacy Assessment Score (GHEA) - Composed of 3 Individual Ratings
研究概览
简要总结
The purpose of the study is to evaluate the efficacy and safety of BAX 855 in severe hemophilia A previously treated (PTP) males, 12 to 65 years of age who are undergoing elective surgical or other invasive procedures.
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
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant requires an elective major or minor surgical, dental or other invasive procedure (e.g. biopsy, endoscopy).
- •Participant and/or legal representative has/have provided signed informed consent.
- •Participant has severe hemophilia A (Factor VIII (FVIII) level <1%) as confirmed by the central lab at screening or a documented FVIII activity level <1%.
- •Participant was previously treated with FVIII concentrates with ≥150 documented exposure days (EDs).
- •Participant is currently receiving prophylaxis or on-demand therapy with FVIII concentrate.
- •Participant has a Karnofsky performance score of ≥60 at screening.
- •Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥200 cells/mm^3, as confirmed by central laboratory at screening.
- •Participant is Hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis as assessed by the investigator.
- •Participant is willing and able to comply with the requirements of the study protocol.
排除标准
- •Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Unit (BU) using the Nijmegen modification of the Bethesda assay) at screening as determined by the central laboratory or at any timepoint prior to screening (≥0.4 BU using the Nijmegen modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay).
- •History of ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
- •Participant has a platelet count <100 x 10^9/L, as confirmed by central laboratory at screening.
- •Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
- •Participant has severe chronic hepatic dysfunction (eg ≥5 X upper limit of normal alanine aminotransferase (ALT), as confirmed by the central laboratory at screening, or a documented International Normalized Ratio (INR) > 1.5).
- •Participant has a known hypersensitivity towards mouse or hamster proteins, polysorbate 80 or to PEG.
- •Participant is currently using or has recently (< 30 days) used pegylated drugs (other than BAX 855) prior to study participation or is scheduled to use such drugs during trial participation.
- •Participant is currently participating in another clinical drug (other than BAX 855) or device study or use of another investigational product or device within 30 days prior to study entry.
- •Participant has a diagnosis of an inherited or acquired hemostatic defect other than hemophilia A.
- •Participant is currently receiving, or scheduled to receive during the course of the study, an immunomodulating drug (eg, systemic corticosteroid agent at a dose equivalent to hydrocortisone >10 mg/day, or alpha interferon) other than anti-retroviral chemotherapy.
- •Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
结局指标
主要结局
Global Hemostatic Efficacy Assessment Score (GHEA) - Composed of 3 Individual Ratings
时间窗: Hemostatic efficacy assessments were performed intraoperatively, postoperatively on day 1 (approximately 24 hours after surgery) and perioperatively at day 14 or discharge (whichever was first).
GHEA=Sum of 1-3 ratings: Excellent: 7-9 (no category \<2), Good: 5-7 (no category \<1), Fair: 3-4 (no category \<1) 1. Intraoperative and 2. Postoperative (postoperative day 1) hemostatic efficacy assessments: Excellent=3: Blood Loss (BL) ≤ than expected for procedure type in non-hemophilic population (NHP) (≤100%), Good=2: BL ≤50% more than expect. for procedure type in NHP (101-150%), Fair=1: BL \>50% more than expect. for procedure type in NHP (\>150%), None=0: Significant bleeding-requiring rescue therapy (RT) 3. Perioperative hemostatic efficacy assessment (day 14 or discharge, whatever is first): Excellent=3: BL and required blood transfusions (BT) less than or similar (≤100%) to that expected for procedure type in NHP, Good=2: BL ≤50% more (101-150%) and BT less than or similar to that expected for procedure type in NHP, Fair=1: BL \>50% more (\>150%) and BT greater than expected in NHP, None=0: Significant bleeding-requiring RT, BT substantially greater than expected in NHP
次要结局
- Intraoperative Blood Loss(From initiation of surgery until end of surgery.)
- Postoperative Blood Loss(From completion of surgery until 24 hours after surgery.)
- Consumption of BAX855(From initial loading dose until discharge for daily weight-adjusted dose and from first infusion (PK/IR) until end of study for total weight-adjusted dose.)
- Pharmacokinetics (PK) - Mean Residence Time (MRT)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.)
- Overall Perioperative Blood Loss(From start of surgery until discharge or day 14, whichever occurred first.)
- Pharmacokinetics (PK) - Area Under the Plasma Concentration/Time Curve From Time 0 to 96 Hours Post-infusion (AUC0-96h)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.)
- Development of Treatment Emerging Binding Antibodies to Factor VIII (FVIII), Treatment Emergent Binding Antibodies to PEGylated Recombinant FVIII (BX855), and Treatment Emerging Binding Antibodies to Polyethylene Glycol (PEG)(Up to 105 days prior to surgery (Screening visit); and End of Study Visit (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).)
- Pharmacokinetics (PK) - Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity (AUC0-∞)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.)
- Pharmacokinetics (PK) - Clearance (CL)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.)
- Transfusion Requirements(From initiation of the surgery to 24 hours after completion of the surgery.)
- Occurrence of Bleeding Episodes and Additional Need for Surgical Intervention(Intra- and post-operative period, until the last intensified treatment after hospital discharge (minor surgery 1-3 days, major surgery average approximately 2 weeks))
- Pharmacokinetics (PK) - Terminal Half-life (T1/2)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.)
- Pharmacokinetics (PK) - Incremental Recovery(IR)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.)
- Development of Treatment Emerging Anti-chinese Hamster Ovary (CHO) Antibodies(Up to 105 days prior to surgery (Screening visit); and End of Study Visit (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).)
- Occurrence of Thrombotic Events(Throughout the entire study period from screening to completion/termination. For each participant the duration of treatment and the entire study period depended on the nature of the invasive procedure (ranged from 43 days to 162 days).)
- Clinically Significant Changes in Vital Signs - Systolic and Diastolic Blood Pressure (BP)(Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.)
- Clinically Significant Changes in Vital Signs - Respiratory Rate(Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.)
- Clinically Significant Changes in Vital Signs - Pulse Rate(Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.)
- Clinically Significant Changes in Routine Laboratory Parameters- Hematology and Chemistry(Throughout the entire study period from screening to completion/termination (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).)
- Pharmacokinetics (PK) - Apparent Volume of Distribution at Steady State (Vss)(PK measurements were done within 30 minutes pre-infusion, and post infusion at 15 (± 5) minutes, 3 hours (± 30 minutes), 9 hours (± 30 minutes), 32 (± 2) hours, 56 (± 4) hours and 96 (± 4) hours.)
- Development of Inhibitory Antibodies to Factor VIII (FVIII)(Up to 105 days prior to surgery (Screening visit); and End of Study Visit (variable for each participant and depends on the nature of the invasive procedure (treatment period ranged from 43 days to 162 days).)
- Clinically Significant Changes in Vital Signs - Body Temperature(Vital signs measurement prior to the PK/IR infusion and 15 minutes post-infusion.)
- Incidence of Severe Allergic Reactions (e.g. Anaphylaxis)(Throughout the entire study period from screening to completion/termination. For each participant the duration of treatment and the entire study period depended on the nature of the invasive procedure (ranged from 43 days to 162 days).)
- Other Investigational Product (IP) - Related Adverse Events(Throughout the entire study period from screening to completion/termination. For each participant the duration of treatment and the entire study period depended on the nature of the invasive procedure (ranged from 43 days to 162 days).)
研究者
研究点 (44)
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