An Open-Label, Multicentre, Long-Term Follow-Up Study to Investigate the Safety and Durability of Response Following Dosing of a Novel Adeno-Associated Viral Vector (FLT180a) in Patients With Haemophilia B
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 10
- 主要终点
- Durability of Response
研究概览
简要总结
Severe haemophilia B (HB) is a bleeding disorder where a protein made by the body to help make blood clot is either partly or completely missing. This protein is called a clotting factor; with severe HB, levels of clotting Factor IX (nine; FIX) are very low and affected individuals can suffer life threatening bleeding episodes. HB mainly affects boys and men (approximately one in every 30,000 males). Current treatment for HB involves intravenous infusions of FIX as regular treatment (prophylaxis) or 'on demand' treatment. On demand treatment is highly effective at stopping bleeding but cannot fully reverse long-term damage that follows after a bleed. Regular treatment can prevent bleeding; however it is invasive for patients and also expensive.
This clinical study aims to investigate the long-term safety and durability of FIX activity in participants who have been dosed with a new gene therapy product (FLT180a) in earlier clinical studies. Following administration, FLT180a results in production of FIX in the participants' liver cells which is then released into the blood stream. The aim is to have the participants' own body produce levels of FIX that allow for clotting to occur as normal as would be seen in a non-HB individual. This would remove the need for prophylaxis or on demand treatment following just a single administration of FLT180a.
Up to 50 participants who have already been administered with FLT180a in the EU and US will take part in this study. Participants will be followed up in this trial until they have reached 15 years after being dosed. Participants will undergo procedures including physical examinations, join assessments, blood tests and liver ultrasounds. Participants will also need to complete a diary to document occurrence of bleeding episodes and record the amount of Factor IX concentrate they receive. Patient reports outcomes including measures of Quality of Life, disability and physical activity will also be collected.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Patients who have previously received FLT180a within a clinical study.
- •Able to give full informed consent and able to comply with all requirements of the study including long-term follow-up for the time frame the study requires.
- •Willing to practice barrier contraception until at least three consecutive semen samples after vector administration are negative for vector sequences.
排除标准
- 未提供
研究组 & 干预措施
FLT180a
Participants who have received gene therapy vector (FLT180a)
干预措施: FLT180a (Biological)
结局指标
主要结局
Durability of Response
时间窗: From entry to 5 years post dosing
Durability of response will be estimated by the rate of decline of the FIX activity observed from study entry (Primary Endpoint)
Primary Safety Measurement
时间窗: From entry to 5 years post dosing
Frequency of treatment-emergent adverse events/reactions (AE/ARs) reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or later (Primary Safety).
次要结局
- Haemostatic Effectiveness - Bleeding Rates(From entry to 5 years post dosing)
- Haemostatic Effectiveness - FIX Concentrate Consumption(From entry to 5 years post dosing)
- FIX Activity Levels including 150% or above(From entry to 5 years post dosing)
- FLT180a effectiveness related to surgical/dental procedures by assessment of measurement of absolute blood loss at Time of surgery, Time of drain removal (if applicable)(From entry to 5 years post dosing)
- FLT180a effectiveness related to surgical/dental procedures by assessment of blood transfusion requirement, volume and number of transfusions at Time of surgery, Time of drain removal (if applicable)(From entry to 5 years post dosing)
- FIX Activity Levels at or below 150%(From entry to 5 years post dosing)
- FIX Activity Levels - Change from baseline(From entry to 5 years post dosing)
- Secondary Safety Measurement(From entry to 5 years post dosing)
- FLT180a effectiveness related to surgical/dental procedures by assessment of consumption of exogenous clotting factors at Time of surgery, Time of drain removal (if applicable)(From entry to 5 years post dosing)
- FLT180a effectiveness related to surgical/dental procedures by assessment of efficacy of haemostasis as judged by surgeon on a 4-point scale at Time of surgery, Time of drain removal (if applicable)(From entry to 5 years post dosing)
- Immune response to the hFIX transgene product (i.e., development of inhibitors) will be assessed by measurement of the level of inhibitors.(From entry to 5 years post dosing)
- Clearance of vector genomes (vgs) in plasma, urine, saliva, stool and semen.(From entry to complete clearance of vgs in all sample pools.)