A Phase 4 Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE® (C1 Inhibitor [Human]) as Prophylactic Therapy in Subjects With Inadequately Controlled Hereditary Angioedema Attacks
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 20
- 试验地点
- 21
- 主要终点
- Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance
研究概览
简要总结
The objectives of the study were:
- To assess the safety and tolerability of escalating doses of CINRYZE.
- To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates.
- To assess the immunogenicity of CINRYZE.
详细描述
Qualifying subjects entered a 3-step dose escalation algorithm:
- Step 1: 1500 Units twice per week (starting dosing regimen for all subjects in the study)
- Step 2: 2000 Units twice per week
- Step 3: 2500 Units twice per week
Each step consisted of 12 weeks of safety monitoring, followed by calculation of average monthly angioedema attack rate based on subject reports of angioedema symptoms (regardless of intensity) and actual duration of therapy for that step.
If a subject was deemed a "success" at a given step and the investigator and medical monitor determined that it was safe for the subject to continue on that dose, the subject entered a 3 month follow-up period at that dose level with continued safety monitoring. The subject could not re-enter the study for purposes of dose escalation during the follow-up period.
If a subject was not deemed a "success," the subject initiated the next highest step of the dose escalation algorithm provided that the investigator and medical monitor agreed that dose escalation was appropriate. If at the end of Step 3 (2500 Units), a subject was not deemed a "success," then the Week 12 visit represented study completion and the subject was referred to the physician who manages their HAE care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for this protocol, subjects must:
- •Be ≥6 years of age and ≥25 kg body weight.
- •Have a confirmed diagnosis of HAE with a documented history of swelling of the face, extremities, gastrointestinal tract, genitalia, or larynx and a history of at least one of the following:
- •C1 INH gene mutation
- •C4 level below the lower limit of the reference range
- •C1 INH antigen level below the lower limit of the reference range
- •Functional C1 INH level below the lower limit of the reference range
- •Family history of HAE (i.e., grandparent, parent, sibling)
- •Have a history of >1.0 HAE attack per month (average) of any severity during the 3 consecutive months prior to screening while receiving the recommended CINRYZE dosing of 1000 Units every 3 to 4 days via intravenous injection.
- •If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
- •If a child, have a parent/legal guardian who is willing and able to provide written informed consent for the child to participate in the study (with assent from the child when appropriate).
排除标准
- •To be eligible for this protocol, subjects must not:
- •Have, as determined by the investigator and/or the sponsor's medical monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
- •Have a history of abnormal blood clotting or other coagulopathy.
- •Be taking prescription anticoagulant medication.
- •Have a history of allergic reaction to CINRYZE or other blood products.
- •Have participated in any other investigational drug study within the past 30 days (other than CINRYZE protocols).
- •Have received any blood products (other than CINRYZE) within 60 days prior to screening.
- •Have any of the following laboratory values at screening:
- •Hemoglobin <8 g/dL
- •White blood cell count <2 x 10^9/L or >20 x 10^9/L
- •Platelet count <50 x 10^9/L or >400 x 10^9/L
- •Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.0 x the upper limit of normal
- •Blood urea nitrogen and/or creatinine >2.0 x the upper limit of normal
- •Be pregnant or breastfeeding.
结局指标
主要结局
Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance
时间窗: 12 to 24 weeks at each dose level
Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.
次要结局
- Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates(12 weeks at each dose level)