NCT02396342已完成1 期
A Phase I/II, Open-label, Uncontrolled, Single-dose, Dose-ascending, Multi-centre Trial Investigating an Adeno-associated Viral Vector Containing a Codon-optimized Human Factor IX Gene (AAV5-hFIX) Administered to Adult Patients With Severe or Moderately Severe Hemophilia B
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 10
- 试验地点
- 7
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
This study evaluates how safe gene therapy treatment with AAV5-hFIX is in adult patients with severe or moderately severe hemophilia B and severe bleeding type.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Age ≥ 18 years
- •Patients with congenital hemophilia B classified as one of the following:
- •Known severe FIX deficiency with plasma FIX activity level < 1% and a severe bleeding phenotype defined by one of the following:
- •Currently on prophylactic FIX replacement therapy for a history of bleeding
- •Currently on on-demand therapy with a current or past history of frequent bleeding defined as four or more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints
- •Known moderately severe FIX deficiency with plasma FIX activity level between ≥ 1% and ≤ 2% and a severe bleeding phenotype defined by one of the following:
- •Currently on prophylactic FIX replacement therapy for a history of bleeding
- •Currently on on-demand therapy with a current or past history of frequent bleeding defined as four or more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints
- •More than 150 previous exposure days of treatment with FIX protein.
- •Acceptance to use a condom during sexual intercourse in the period from Investigational Medicinal Product (IMP) administration until AAV5 has been cleared from semen, as evidenced by the central laboratory from negative analysis results for at least 3 consecutively collected semen samples (this criterion is applicable also for subjects who are surgically sterilized)
- •Following receipt of verbal and written information about the trial, the subject has provided signed informed consent before any trial related activity is carried out.
排除标准
- •History of FIX inhibitors measured to be ≥ 0.6 Bethesda Units (BU)/mL
- •FIX inhibitors ≥ 0.6 BU/mL at Visit 1 (measured by the local laboratory)
- •Neutralizing antibodies against AAV5 at Visit 1 (measured by the central laboratory)
- •Visit 1 laboratory values (measured by the central laboratory):
- •alanine aminotransferase > 2 times upper normal limit
- •aspartate aminotransferase > 2 times upper normal limit
- •total bilirubin > 2 times upper normal limit
- •alkaline phosphatase > 2 times upper normal limit
- •creatinine > 1.5 times upper normal limit
- •Positive HIV serological test at Visit 1, not controlled with anti-viral therapy as shown by cluster of differentiation 4+ counts ≤ 200 per μL or by a viral load of >200 copies per mL (measured by the central laboratory)
- •Active infection with Hepatitis B or C virus as reflected by Hepatitis B Surface Antigen (HBsAg), Hepatitis B extracellular Antigen (HBeAg), Hepatitis B Virus DeoxyriboNucleic Acid (HBV DNA) or Hepatitis C Virus RiboNucleic Acid (HCV RNA) positivity, respectively, at Visit 1 (measured by the central laboratory).
- •History of Hepatitis B or C exposure, currently controlled by antiviral therapy
- •Any coagulation disorder other than hemophilia B
- •Thrombocytopenia, defined as a platelet count below 50 × 10E9 / L, at Visit 1 (measured by the central laboratory)
- •Body mass index < 16 or ≥ 35 kg/m2
- •Planned surgery for the initial 6 months after IMP administration in this trial
- •Previous arterial or venous thrombotic event (e.g. acute myocardial infarction, cerebrovascular disease and venous thrombosis)
- •Active severe infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, 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 protocol procedures or with the degree of tolerance to the IMP
- •Known significant medical condition including disseminated intravascular coagulation, fibrinolysis and liver fibrosis which, in the opinion of the investigator, may confound, contraindicate or limit the interpretation of either safety or efficacy data
- •Known history of an allergic reaction or anaphylaxis to FIX products
- •Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients
- •Previous gene therapy treatment and/or previous participation in a gene therapy clinical trial
- •Receipt of an experimental agent within 60 days prior to Visit 1
- •Current participation or anticipated participation within one year after IMP administration in this trial in any other interventional clinical trial involving drugs or devices.
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: From AMT-060 infusion through end of study (5 years post-dose)
次要结局
- Total Consumption of FIX Replacement Therapy(From AMT-060 infusion through end of study (5 years post dose).)
- FIX-replacement-therapy-free FIX Activity(From AMT-060 infusion through end of study (5 years post-dose))
- Total IgG and IgM Antibody Titers to AAV5(AMT-060 infusion through end of study (5 years post dose))
- Number of Subjects Developing Neutralizing Antibodies to AAV5(From AMT-060 infusion through end of study (5 years post dose))
- Total Annualized Bleeding Rate (ABR)(From AMT-060 infusion through end of study (5 years post-dose))
- Change From Baseline in Short Form-36 (SF-36) Quality of Life (QoL) Scores(From AMT-060 infusion through the end of study (5 years post dose))
- Time to Vector DNA Stopped Shedding From Blood, Nasal Secretions, Saliva, Urine, Feces, and Semen(From AMT-060 infusion through end of study (5 years post dose).)
- Number of Subjects With Antibodies to FIX(From AMT-060 infusion through the end of study (5 years post dose))
- Number of Subjects With FIX Inhibitors(From AMT-060 infusion through the end of study (5 years post dose))
- Number of Subjects With Clinically Significant Inflammatory Markers: IL-1β, IL-2, IL-6, INFγ, MCP-1(From AMT-060 infusion through 18 weeks post dose)
- Number of Subjects With a Positive AAV5 Capsid-specific T Cell Response(From AMT-060 infusion through 26 weeks post-dose)
研究者
研究点 (7)
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