A phase IIIb, Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Patients From Birth to 12 Months of Age with Hemophilia A without Inhibitors
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 31
- 试验地点
- 12
- 主要终点
- 1. Number of treated bleeds over time
研究概览
简要总结
To evaluate the efficacy, safety, pharmacokinetic (PK) profile, pharmacodynamics (PD) parameters and immune response to treatment of emicizumab
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Overall Design
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •No history of documented FVIII inhibitor (i.e., < 0.6 BU/mL), FVIII drug-elimination half-life < 6 hours, or FVIII recovery < 66%
- •Mandatory receipt of vitamin K prophylaxis according to local standard practice
- •Diagnosis of severe congenital hemophilia A (intrinsic FVIII level < 1%)
- •A negative test for FVIII inhibitor (i.e., < 0.6 Bethesda units [BU]/mL) locally assessed during the 2-week screening period for all patients
- •Previously untreated patients (PUPs) or minimally treated patient (MTPs) (i.e., up to 5 days of exposure with hemophilia-related treatments, such as plasma-derived FVIII, recombinant FVIII, fresh frozen plasma, cryoprecipitate, or whole blood products)
- •Documentation of the details of the hemophilia-related treatments received since birth and documentation of the details of the bleeding episodes since birth
排除标准
- •Inherited or acquired bleeding disorder other than severe hemophilia A
- •Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study
- •Current active severe bleed, such as intracranial hemorrhage (ICH)
- •History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
- •Patients who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA, such as thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome) in the investigator's judgment
- •Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
结局指标
主要结局
1. Number of treated bleeds over time
1. Number of treated bleeds over time
2. Number of all bleeds over time
2. Number of all bleeds over time
3. Number of treated spontaneous bleeds over time
3. Number of treated spontaneous bleeds over time
4. Number of treated joint bleeds over time
4. Number of treated joint bleeds over time
5. Joint health, as assessed through use of the Hemophilia Joint Health Score (HJHS) and magnetic resonance imaging (MRI) score of specific joints at specified timepoints only during the 7-year long-term follow-up (LTFU) period
5. Joint health, as assessed through use of the Hemophilia Joint Health Score (HJHS) and magnetic resonance imaging (MRI) score of specific joints at specified timepoints only during the 7-year long-term follow-up (LTFU) period
6. Incidence and severity of adverse events, with severity determined according to WHO Toxicity Grading Scale
6. Incidence and severity of adverse events, with severity determined according to WHO Toxicity Grading Scale
7. Incidence of thromboembolic events and thrombotic microangiopathy (TMA)
7. Incidence of thromboembolic events and thrombotic microangiopathy (TMA)
8. Change from baseline in physical examination findings
8. Change from baseline in physical examination findings
9. Change from baseline in vital signs
9. Change from baseline in vital signs
10. Incidence of laboratory abnormalities
10. Incidence of laboratory abnormalities
11. Incidence and severity of injection-site reactions
11. Incidence and severity of injection-site reactions
12. Incidence of adverse events leading to study drug discontinuation
12. Incidence of adverse events leading to study drug discontinuation
13. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events
13. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events
14. Plasma trough concentrations (Ctrough) of emicizumab prior to study drug administration
14. Plasma trough concentrations (Ctrough) of emicizumab prior to study drug administration
15. Effect of emicizumab on PD parameters, including aPTT, thrombin generation (TG), and reported FVIII activity, as well as FIX antigen and FX antigen (emicizumab substrates) levels prior to study drug
15. Effect of emicizumab on PD parameters, including aPTT, thrombin generation (TG), and reported FVIII activity, as well as FIX antigen and FX antigen (emicizumab substrates) levels prior to study drug
次要结局
- Not applicable
研究者
Trial Information System - TISL
Scientific
F. Hoffmann-La Roche AG