A Phase I/IIa Dose Escalation Study of Repeated Administration of "CYT107" (Glyco-r-hIL-7) Add-On Treatment in Genotype 1 or 4 Hcv Infected Patients Resistant to Pegylated Interferon-Alpha and Ribavirin
试验速览
- 阶段
- 1 期
- 发起方
- Cytheris SA
- 入组人数
- 18
- 试验地点
- 8
- 主要终点
- To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin
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 standard bi-therapy in patients with Hepatitis C chronic infection identified as non responders to the standard bi-therapy alone.
详细描述
This is a Phase I/IIa inter-patient dose-escalation study assessing weekly doses of Interleukin-7 (CYT107) in adult patients infected by virus genotype 1 or 4 of Hepatitis C and resistant to standard treatment with Peg-Interferon and Ribavirin (bitherapy).
The dose escalation is aimed at establishing the safety of a biologically active doses of CYT107 added to the combination therapy of pegylated interferon-alpha and ribavirin. At each dose level, study patients will receive one subcutaneous administration of CYT107 per week for a total of 4.
Groups of 6 patients will be entered at each dose level of CYT107. Three dose levels are planned.
Eligible patients initially receive bi-therapy for 6-10 weeks. Thereafter, CYT107 is added for a cycle of four weekly injections at a defined dose level while standard bi-therapy continues for 9 weeks after CYT107 treatment discontinuation. The patients are then followed on a regular basis until reaching 48 weeks after the CYT107 treatment. The duration of study is approximatively 60 weeks with 20-25 weeks of bi-therapy.
Participants will have 1 overnight hospitalization and 15 clinic visit on a period of 60 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Genotype 1 or 4 infected patients
- •Age > 18 years
- •Absence of viral response to previous treatments with pegylated interferon-alpha plus ribavirin defined as:
- •Absence of early viral response (EVR) with detectable HCV and with a decrease HCV RNA load < 2 logs, measured by a quantitative PCR tests after 12 weeks of treatment, as compared to baseline levels measured by a similar technique; or
- •Absence of end of treatment response defined by detectable HCV RNA at the end of treatment (24 weeks or 48 weeks)
- •Metavir ≤ F3 assessed by biopsy in the last 12 months or by fibroscan if Fibroscan® result < 10 kPa in the last 6 months (biopsy can be avoided)
排除标准
- •Active infection by HBV (positive HBs Ag or positive anti HBc antibodies with a detectable HBV DNA viral load).
- •Infection by HIV-1 and /or HIV-2
- •Apart from HCV infection, presence of active infection requiring a specific treatment or a hospitalization
- •Other liver disease (notably from alcoholic, metabolic or immunological origin)
- •Body mass index (BMI) > 30kg/m2
- •Relapse after previous response to pegylated IFN alpha and ribavirin therapy
- •Any history of malignancy apart from curatively treated basal cell carcinoma or in situ cervical carcinoma
- •History of clinical autoimmune disease or active auto-immune disease
- •History of severe asthma, presently on chronic medications
- •Significant cardiac or pulmonary disease
- •Prior solid organ or hematopoietic cell transplantation
- •Dialyzed patient
- •Inability to give informed consent
研究组 & 干预措施
CYT107
干预措施: Interleukin-7 (Drug)
结局指标
主要结局
To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin
时间窗: 12 weeks after the start of IL-7
次要结局
- To characterize pharmacokinetics and pharmacodynamics of CYT107(12 weeks after the start of IL-7)
- To evaluate in the context of a dose escalation strategy the potential anti-viral effect of CYT107(12 weeks after the start of IL-7)
- To evaluate the immune specific response to HCV(12 weeks after the start of IL-7)
- To document the long-term safety and viral load variations(48 weeks after the start of IL-7)