A Phase Randomized Open Labelled Controlled Dose Escalation Study of Repeated Administration of "CYT107" (Glyco-r-hIL-7) Added on Antiviral Treatment and Vaccination in HBeAg-negative Chronic Hepatitis B-infected Patients
试验速览
- 阶段
- 1 期
- 发起方
- Cytheris SA
- 入组人数
- 24
- 试验地点
- 8
- 主要终点
- To determine the short and long-term safety and biological activity of CYT107 in patients with a HBeAg-negative chronic hepatitis B who have, at screening a HBV DNA undetectable stable for at least 3 months with antiviral treatment.
研究概览
简要总结
This study is designed to evaluate the safety of biological active dose of a new experimental drug, IL-7, in combination with anti viral therapy and vaccine in patients with Hepatitis B chronic infection.
详细描述
This is a Phase I/IIa inter-patient dose-escalation study assessing weekly doses of Interleukin-7 (CYT107) in HBeAg-negative chronic hepatitis B infected adult patients. The dose escalation is aimed at establishing the safety of a biologically active doses of CYT107 added to the current antiviral therapy with entecavir or tenofovir and vaccination or not. At each dose level, study patients will receive one subcutaneous administration of CYT107 per week for a total of 4.
Groups of 8 patients will be entered at each dose level of CYT107. Three dose levels are planned.
At each dose level, patients are randomized between 2 arms of treatment: tritherapy (CYT107, vaccine and antiviral treatment) or bitherapy (CYT107 and vaccine). Each treatment group is composed of 4 patients, 3 receiving experimental treatments, 1 just the current antiviral treatment (control patient).
According to the treatment arm, eligible patients initially receive a vaccine if in treatment group of tritherapy, thereafter, CYT107 is added for a cycle of four weekly injections (if not a control patient) at a defined dose level. If in treatment group of tritherapy, patients will receive 2 additional doses of vaccine.
The treatment phase for the tritherapy group is from first vaccine D0 to last vaccine W12 and includes CYT107 administration from W4 to W7.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Chronic HBV-infected patients
- •HBeAg-negative patients
- •Age > 18 years
- •Patients with active chronic hepatitis at the start of the antiviral treatment
- •Patient with a HBV DNA undetectable (<70 copies/ml) stable for at least 3 months under entecavir or tenofovir treatment.
- •Ongoing treatment by entecavir or tenofovir at screening Note: previous treatment with pegylated IFN monotherapy, before the start of entecavir or tenofovir, is acceptable
排除标准
- •Infection by HCV
- •Infection by HIV-1 and /or HIV-2
- •Apart from HBV infection, presence of active infection requiring a specific treatment or a hospitalization
- •Previous treatment by lamivudine and/or nucleosides analogues
- •Inactive carrier
- •Cirrhosis
- •Other liver disease (notably from alcoholic, metabolic or immunological origin)
- •History of clinical autoimmune disease or active auto-immune disease
- •Type I diabetes mellitus
- •Severe asthma, presently on chronic medications
研究组 & 干预措施
Tritherapy: CYT107+ vaccine+ antiviral
干预措施: CYT107+GenHevac+entecavir or tenofovir (Drug)
Bitherapy: CYT107 + antiviral
干预措施: CYT107+ entecavir or tenofovir (Drug)
结局指标
主要结局
To determine the short and long-term safety and biological activity of CYT107 in patients with a HBeAg-negative chronic hepatitis B who have, at screening a HBV DNA undetectable stable for at least 3 months with antiviral treatment.
时间窗: Week 12
次要结局
- To characterize the pharmacokinetics and pharmacodynamics of CYT107 in humans chronically infected with HBV.(Week 12)
- To assess the effects of the tri-therapy (CYT107 + HBV vaccine + antiviral treatment) versus bi-therapy (CYT107 + antiviral treatment) versus control (antiviral treatment) on the markers of the HBV infection (antiviral activity)at W16 weeks and W52(Week 12 and Week 52)
- To quantify the effects of the tri-therapy (CYT107 + HBV vaccine + antiviral treatment) versus bi-therapy (CYT107 + antiviral treatment) versus control (antiviral treatment) on the immune system at W16 weeks(Week 16)