Response Guided Therapy (RGT) for Boceprevir Combined With Peginterferon Alpha-2b Plus Ribavirin in Naïve Hispanic Patients With Genotype 1 Hepatitis C Infection
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- SVR based on intention to treat analysis
研究概览
简要总结
Hypothesis Response guided therapy improves significantly the overall SVR in Hispanics compared to historical control. There is no difference in SVR between patients with an undetectable HCV RNA at week 8 and week 28 who received a 4 week lead-in of PR plus 24 weeks of PR+BOC based treatment and patients with detectable HCV RNA at week 8 and undetectable HCV RNA at week 24 who received a lead-in of PR plus 32 weeks PR+BOC followed by based therapy and 12 weeks of PR.
详细描述
STUDY DESIGN AND ENROLLMENT Open label single arm pilot study enrolling Hispanic patients with HCV genotype 1 and naive to pegylated interferon and BOC treatment.
Definition of BOC RGT:
All patients will receive 4 weeks of PR (lead-in), and BOC will be added at the beginning of week 5. Patients who have an undetectable HCV RNA at week 8 and week 24 will receive 24 weeks of PR and BOC (28 weeks total treatment); patients who have a detectable HCV RNA at week 8, but an undetectable HCV RNA at week 24, will receive an additional 32 weeks of PR and BOC, followed by 12 weeks of PR (48 weeks total treatment).
Patients with cirrhosis or bridging fibrosis (Stage 4 fibrosis) will receive 4 weeks of lead in followed by 44 weeks of BOC and PR (total 48 weeks).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for this trial, patients must have documentation of the following:
- •Male or female > 18 years old
- •HCV genotype-1 infection
- •Liver biopsy consistent with Chronic Hepatitis C (CHC) within the last 3 years
- •No previous treatment with any anti-HCV therapy (approved or investigational)
- •For women of childbearing potential, a negative urine pregnancy test result documented within 24 hours prior to the first dose of any study drug (BOC, PEG-INF alfa-2b, or ribavirin). Additionally, all female patients of childbearing potential and all males with female partners of childbearing potential must use two forms of effective contraception (combined) during study treatment and for 6 months after treatment.
- •Willingness to give written informed consent and to participate in and comply with requirements of the study
排除标准
- •Patients with any of the following will not be eligible for participation:
- •Infection with HCV other than genotype 1
- •History or other evidence of a medical condition associated with chronic liver disease other than CHC (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
- •History or other evidence of decompensated liver disease (e.g., coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, bleeding from esophageal varices) or a Child-Pugh score > 6 (see Appendix 1)
- •Infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or HIV as demonstrated by a positive test at screening for anti-HAV immunoglobulin M (IgM) antibodies (Ab), hepatitis B surface antigen, anti-hepatitis B core protein IgM Ab, or anti-HIV antibodies
- •History of having received IFN, PEG-IFN, ribavirin, viramidine, levovirin, or investigational HCV protease or polymerase inhibitors at any previous time, or any other systemic antiviral therapy with established or perceived activity against HCV within 3 months prior to enrollment.
- •Pregnant or breastfeeding
- •Male partners of females who are pregnant or breastfeeding
- •Hemoglobin concentration < 12 g/dL in females or < 13 g/dL in males or any patient with an increased risk for anemia (e.g., thalassemia, sickle cell anemia, spherocytosis, history of gastrointestinal bleeding) or for whom anemia would be medically problematic
- •Absolute neutrophil count (ANC) < 1000 cells/mm3
- •Platelet count < 70,000 cells/mm3
- •Receipt of stimulating factors such as granulocyte colony stimulating factor (G-CSF), erythropoietin, or other therapeutic agents to elevate hematology parameters to facilitate patient entry into the study
- •Serum creatinine concentration > 1.5 times the upper limit of normal (ULN)
- •History of severe psychiatric disease, including psychosis and/or depression, characterized by a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease
- •Poorly controlled thyroid dysfunction
- •History of cardiac disease (e.g., New York Heart Association functional class II, III, or IV, myocardial infarction within the last 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina, or other significant cardiovascular diseases. In addition, patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well tolerated.
- •History of uncontrolled severe seizure disorder within the last year
- •Patients treated previously with protease or polymerase inhibitors
- •Coadministration of drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events including those in Appendix
- •Coadministration with potent CYP3A4/5 inducers, where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy.
研究组 & 干预措施
Hispanic, HCV genotype 1
Historical group will be a continuous group of Hispanic patients with genotype 1 who were naive to treatment and completed or initiated 48 weeks of pegylated interferon and ribavirin. Patients, who discontinued the treatment due to side effects, adherence issues, or treatment failure, will be included and analyzed based on intention to treat analysis. All patients will be stratified according to their SVR, relapse and no response rate. RVR, EVR, and ETR will be also collated and compared to the study group.
干预措施: Boceprevir (Drug)
结局指标
主要结局
SVR based on intention to treat analysis
时间窗: 24 weeks
Patients who have detectable HCV RNA at week 24 must have study treatment discontinued.
次要结局
- BDI II score 31 or above(48 weeks)
- Tolerance(48 weeks)
研究者
Zeid Kayali, MD
Associate Professor of Medicine
Arrowhead Regional Medical Center