NCT06003387招募中3 期
Phase 3b, Open-label, Multicenter, Single-dose Study Investigating Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B With Detectable Pretreatment AAV5 Neutralizing Antibodies
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- CSL Behring
- 入组人数
- 35
- 试验地点
- 55
- 主要终点
- Annualized Bleeding Rate (ABR)
研究概览
简要总结
The purpose of this study is to assess the risk of bleeding due to failure of expected pharmacological action of CSL222 in adults with severe or moderately severe hemophilia B with detectable pretreatment AAV5 Nabs.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Considered legally an adult, as defined by country regulations.
- •Has congenital hemophilia B with known severe or moderately severe FIX deficiency (less than or equal to [<=] 2% of normal circulating FIX) for which the participant is on continuous routine FIX prophylaxis.
- •Has 2 consecutive detectable AAV5 NAb titer results between Screening and Visit L-Final using a validated AAV5 NAb assay (based on central laboratory results).
- •Has greater than (>) 150 previous exposure days to FIX replacement therapy.
- •Has been on stable FIX prophylaxis for at least 2 months before Screening.
- •Has demonstrated capability to independently, accurately, and in a timely manner complete the eDiary during the Lead-in Period, as judged by the investigator.
- •Acceptance to adhere to contraception guidelines.
- •Able to provide informed consent after receipt of verbal and written information about the study.
- •Investigator believes that the participant (or the participant's legally acceptable representative[s]) understands the nature, scope, and possible consequences of the study and is able to adhere to the study procedures.
排除标准
- •History of FIX inhibitors or positive FIX inhibitor test at Prescreening, Screening or Visit L-Final (based on central laboratory results).
- •Screening or Visit L-Final laboratory values (based on central laboratory results) of total bilirubin > 2 × the upper limit of normal (ULN) (except if caused by Gilbert's syndrome).
- •Screening or Visit L-Final laboratory values (based on central laboratory results) of any of the following laboratory abnormalities:
- •ALT > 2 × the ULN
- •AST > 2 × the ULN
- •Alkaline phosphatase > 2 × the ULN
- •Serum creatinine > 2 × the ULN
- •Hemoglobin less than (<) 8 g/dL
- •Any condition other than hemophilia B resulting in an increased bleeding tendency.
- •Thrombocytopenia, defined as a platelet count <50 × 10^9/L, at Screening or Visit L Final (based on central laboratory results).
- •Any uncontrolled or untreated infection (human immunodeficiency virus [HIV], hepatitis B virus [HBV] and hepatitis C virus [HCV], or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiovascular, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, alcoholism, drug dependency, or any other psychological disorder evaluated by the investigator to interfere with adherence to the clinical study protocol procedures or with the degree of tolerance to CSL
- •Known history of allergy to corticosteroids or known medical condition that would require chronic administration of oral corticosteroids.
- •Known uncontrolled allergic conditions or allergy / hypersensitivity to any component of the CSL222 excipients (ie, sucrose, potassium chloride, potassium dihydrogen phosphate, sodium chloride, and disodium hydrogen phosphate).
- •Previous AAV5 gene therapy treatment.
- •Receipt of an experimental agent or device within 60 days before Screening until the end of the study.
研究组 & 干预措施
CSL222
Experimental
Participants will receive CSL222 as a single intravenous (IV) infusion of 2 × 10^13 genome copies per kilogram (gc/kg) on Day 1.
干预措施: CSL222 (AAV5-hFIXco-Padua) (Genetic)
结局指标
主要结局
Annualized Bleeding Rate (ABR)
时间窗: Months 7 to 18 after CSL222 treatment
The total bleeding episodes will be analyzed. ABR is calculated as the total bleeding episodes divided by the total time at risk.
次要结局
- Number of participants with Treatment Emergent Adverse Events (TEAEs)(Up to 60 months after CSL222 treatment)
- Percentage of participants with TEAEs(Up to 60 months after CSL222 treatment)
- Number of TEAEs(Up to 60 months after CSL222 treatment)
- Change in Liver ultrasound(Up to 60 months after CSL222 treatment)
- Number of participants who develop Factor IX (FIX) Inhibitors(Up to 60 months after CSL222 treatment)
- Percentage of participants who develop FIX Inhibitors(Up to 60 months after CSL222 treatment)
- Change in hematology and biochemistry parameters(Up to 60 months after CSL222 treatment)
- Percentage of participants with clinically significant increase in ALT or AST(Up to 60 months after CSL222 treatment)
- Percentage of participants with clinically significant AFP(Baseline and up to 60 months after CSL222 treatment)
- Number of participants with clinically significant increase in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)(Up to 60 months after CSL222 treatment)
- Corticosteroid use for ALT or AST increases after CSL222 treatment(Up to 60 months after CSL222 treatment)
- Number of participants with clinically significant Alpha-fetoprotein (AFP)(Baseline and up to 60 months after CSL222 treatment)
- Number of participants with infusion related reactions or hypersensitivity reactions(Throughout CSL222 infusion period and up to 60 months after CSL222 treatment)
- Change in the Uncontaminated Endogenous FIX activity(Baseline and up to Months 6, 12, and 18 after CSL222 treatment)
- Percentage of participants remaining free of continuous FIX prophylaxis(Months 7 to 18 after CSL222 treatment)
- Percentage of participants with infusion related reactions or hypersensitivity reactions(Throughout CSL222 infusion period and up to 60 months after CSL222 treatment)
- Annualized consumption of FIX replacement therapy(Months 7 to 18 after CSL222 treatment)
- Annualized infusion rate of FIX replacement therapy(Months 7 to 18 after CSL222 treatment)
- Number of participants remaining free of continuous FIX prophylaxis(Months 7 to 18 after CSL222 treatment)
- ABR for spontaneous bleeding episodes(Months 7 to 18 after CSL222 treatment)
- ABR for joint bleeding episodes(Months 7 to 18 after CSL222 treatment)
- ABR for FIX-treated bleeding episodes(Months 7 to 18 after CSL222 treatment)
- Correlation analysis of FIX activity levels with baseline AAV5 NAb titers(Months 7 to 18 after CSL222 treatment)
- Number of participants with new target joints and resolved pre-existing target joints(Months 7 to 18 after CSL222 treatment)
- Number of participants with zero bleeding episodes and zero FIX-treated bleeding episodes(Months 7 to 18 after CSL222 treatment)
- Percentage of participants with zero bleeding episodes and zero FIX-treated bleeding episodes(Months 7 to 18 after CSL222 treatment)
- Change in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Overall Score(Baseline and up to 18 months after CSL222 treatment)
- Number of Participants with Uncontaminated Endogenous FIX Activity of Greater than or Equal to (>=) 5%(Months 7 to 18 after CSL222 treatment)
- Change in the EQ-5D-5L Index Scores(Baseline and up to 18 months after CSL222 treatment)
- Percentage of Participants with Uncontaminated Endogenous FIX Activity of >= 5%(Months 7 to 18 after CSL222 treatment)
研究者
研究点 (55)
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