Emicizumab PUPs and Nuwiq ITI Study
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 8
- 主要终点
- Cumulative incidence of inhibitors to FVIII
研究概览
简要总结
This study prospectively investigates the safety, FVIII immunogenicity, and hemostatic efficacy of prophylactic HEMLIBRA® given with a concomitant low dose recombinant factor VIII (rFVIII) known as NUWIQ®, in HA infants and children <3 years old who have had little to no previous exposure to FVIII. In addition, the study investigates the safety and efficacy of a novel FVIII ITI regimen in children <21 with existing low and high titer inhibitors (LTI and HTI).
详细描述
Hemophilia A (HA) is a congenital bleeding disorder caused by deficient or dysfunctional factor VIII (FVIII) which leads to bleeding correlated with severity. Management is focused on FVIII replacement in reaction to a bleed or preventive as prophylaxis. Effective treatment is complicated by the: (1) difficulty to administer standard replacement therapy via intravenous injection especially in infants and young children; and (2) development of inhibitors (FVIII neutralizing antibodies). Inhibitors can increase morbidity and mortality and exponentially raise the cost of health care. Although inherited and environmental risk factors for inhibitor formation have been identified, there is no effective strategy to prevent inhibitors from developing. Emicizumab (HEMLIBRA®) was recently approved by the Food and Drug Administration (FDA) in infants, children, and adults with congenital hemophilia A, with and without inhibitors, and offers hemostatic efficacy while reducing the burden of administration since it is given weekly, biweekly (every 2 weeks), or monthly via subcutaneous (SQ) route compared to the intravenous (IV) route of FVIII.
This study prospectively investigates the safety, FVIII immunogenicity, and hemostatic efficacy of prophylactic HEMLIBRA® given with a concomitant low dose recombinant factor VIII (rFVIII) known as NUWIQ®, in HA infants and children <3 years old who have had little to no previous exposure to FVIII. In addition, the study investigates the safety and efficacy of a novel FVIII ITI regimen in children <21 with existing low and high titer inhibitors (LTI and HTI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Untreated/minimally treated moderate HA no inhibitors
Previously untreated patients (PUPs) and minimally treated patients (MTPs) <3 years of age with moderately severe (≤2% FVIII) HA and no inhibitors.
干预措施: Nuwiq (low dose protocol) (Drug)
Untreated/minimally treated moderate HA no inhibitors
Previously untreated patients (PUPs) and minimally treated patients (MTPs) <3 years of age with moderately severe (≤2% FVIII) HA and no inhibitors.
干预措施: HEMLIBRA (Drug)
Treated any moderate HA with existing inhibitors
Children <21 years of age with moderately severe (≤2% FVIII) HA and with already existing inhibitors (LTI or HTI).
干预措施: HEMLIBRA (Drug)
Treated any moderate HA with existing inhibitors
Children <21 years of age with moderately severe (≤2% FVIII) HA and with already existing inhibitors (LTI or HTI).
干预措施: Nuwiq (Atlanta protocol) (Drug)
结局指标
主要结局
Cumulative incidence of inhibitors to FVIII
时间窗: Duration of the follow up (up to 36 months)
Cumulative incidence of inhibitors to FVIII will be recorded
Number of Immune Tolerance Induction (ITI) success cases
时间窗: Duration of the follow up (up to 36 months)
ITI success case is confirmed if three of below are criteria met: 1. Inhibitor titre \< 0.6 BU/mL for at least 2 consecutive measurements 2. FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg BW approximately 15 to 30 min post-injection 3. Half-life of FVIII ≥ 6 h
Number of Immune Tolerance Induction (ITI) partial success cases
时间窗: Duration of the follow up (up to 36 months)
ITI partial success case is confirmed if two of below criteria are met: 1. Inhibitor titre \< 0.6 BU/mL for at least 2 consecutive measurements 2. FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg BW approximately 15 to 30 min post-injection 3. Half-life of FVIII ≥ 6 h
Number of Immune Tolerance Induction (ITI) partial response cases
时间窗: Duration of the follow up (up to 36 months)
ITI partial response case is confirmed if one of below criteria is met: 1. Inhibitor titre \< 0.6 BU/mL for at least 2 consecutive measurements 2. FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg BW approximately 15 to 30 min post-injection 3. Half-life of FVIII ≥ 6 h
Number of Immune Tolerance Induction (ITI) partial failure cases
时间窗: Duration of the follow up (up to 36 months)
ITI partial failure case is confirmed if none of below criteria are met, but participant who initially had a high-titre inhibitor (≥ 5 BU/mL) has a low-titre inhibitor (\< 5 BU/mL) at end of ITI. 1. Inhibitor titre \< 0.6 BU/mL for at least 2 consecutive measurements 2. FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg BW approximately 15 to 30 min post-injection 3. Half-life of FVIII ≥ 6 h
Number of Immune Tolerance Induction (ITI) failure cases
时间窗: Duration of the follow up (up to 36 months)
ITI failure case is confirmed if none of below criteria are met: 1. Inhibitor titre \< 0.6 BU/mL for at least 2 consecutive measurements 2. FVIII recovery ≥ 66% of the predefined reference value of 1.5% IU/kg BW approximately 15 to 30 min post-injection 3. Half-life of FVIII ≥ 6 h
次要结局
- Change in blood levels of anti-Emicizumab antibodies(Weekly x4 (±3 days), then monthly (±7 days) up to 36 months)
- Number of infusions of Nuwiq/Novo7 for treatment of an acute bleeding episode(Duration of the follow up (up to 36 months))
- Number of infusions of rFVIII or rFVIIa for treatment of an acute bleeding episode(Duration of the follow up (up to 36 months))
- Number of joint bleeding events over time (≥3 bleeds in the same joint over the last 24 weeks)(6 months follow up)
- Annualized bleeding rate (ABR)(Duration of the follow up (up to 36 months))
- Change in blood levels of emicizumab (HEMLIBRA®) in young children (1 month to 24 months of age)(Weekly for 4 weeks, monthly for 5 months, and every 3 months until study end (up to 36 months))
- Number of target joint bleeding events over time (≥3 bleeds in the same joint over the last 24 weeks)(12 months follow up)
- Number of adverse events(Duration of the follow up (up to 36 months))
- Change in blood levels of anti-FVIII antibodies(Weekly x4 (±3 days), then monthly (±7 days) up to 36 months)
- Microbiota composition of stool in infants with vs. without inhibitors(Duration of the follow up (up to 36 months))
- Change in CATCH scale score(Baseline, 36 months)
- Change in Adapted Inhib-QoL scale score(Baseline, 36 months)
研究者
Robert Sidonio
Associate Professor
Emory University