A Phase I/II, Open Clinical Trial to Assess the Safety, Tolerability and Efficacy of a Fixed Dose Combination Therapy of: Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (Peg-IFN Alpha-2a) and Ribavirin (RBV) in Chronic Hepatitis C Genotype 1 Infected Subjects Who Failed to Respond Following a Course of Peg-IFN and RBV Therapy (SoC).
试验速览
- 阶段
- 1 期
- 入组人数
- 36
- 主要终点
- Change from baseline in physical examination
研究概览
简要总结
The study is aimed to investigate the safety, tolerability and efficacy of a fixed dose combination therapy of: Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (PEG-IFN alpha-2a) and Ribavirin (RBV) in Chronic Hepatitis C Genotype 1 Infected adult subjects who failed to respond following a course of PEG-IFN and RBV Therapy.
详细描述
This is a phase I/II, open clinical trial to assess the safety, tolerability and preliminary efficacy data of a fixed dose combination therapy of: HCQ, Peg-IFN alpha-2a and RBV in chronic hepatitis C genotype 1 infected subjects who failed to respond following a course of Peg-IFN and RBV Therapy (SoC). The study is a single center trial to be conducted at the Department of Gastroenterology & Hepatology, at Sheba Medical Center, Tel Hashomer, Israel.
Overall, thirty six (36) patients will be recruited. All patients enrolled will have a documented history of chronic HCV disease and being non-responder on earlier Peg-IFN based treatment lasting for at least 12 consecutive weeks prior to study enrolment.
The expected duration of patient screening period prior to enrollment into this study is in-between six weeks (42 days) up to 2 days prior to the study enrollment day at visit 2 (verification of compliance with inclusion/exclusion criteria including clinical laboratory results). Eligible patients will be enrolled into the study and will be observed twice on the first week of the study, once a week during the initiation of the treatment period at weeks 2,3 and week 4, later during the treatment period once a month at weeks 8-48 and at two follow up visits post treatment to take place at week 60 and 72 (allowing a time window of ± 5 days for all visits).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females between 18 and 70 years old.
- •Subjects diagnosed to have positive HCV antibodies using a third generation test.
- •Subject is diagnosed to have detectable HCV RNA by PCR.
- •Liver biopsy or FibroTest showing a METAVIR score ≥F2 and/or ≥A
- •Subject diagnosed to have compensated liver disease.
- •Subject is non-responder (null or partial) on prior Peg-IFN and RBV based treatment lasting for at least 12 consecutive weeks.
- •Treatment not discontinued due to intolerability to Peg-IFN or RBV.
- •Subjects able to comprehend and give informed consent for participation in this study.
- •Subject is willing to be treated and commit to all visits.
排除标准
- •Anti HCV therapy contraindications.
- •Subject is identified as a relapser on prior Peg-IFN and RBV based treatment.
- •Hypersensitivity to one of the three drugs (HCQ, Peg-IFN, RBV).
- •Patient has Anaemia,neutropenia, thrombocytopenia, elevated bilirubin levels, elevated ALT and/or AST, or elevated creatinin and INR greater than 1.
- •Concomitant liver disease other than hepatitis C: chronic hepatitis B, alcoholic liver disease, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency.
- •Decompensated cirrhosis (Child Pugh >A).
- •Clinical evidence for hepatocellular carcinoma.
- •Human immunodeficiency virus co-infection.
- •Major uncontrolled psychiatric illness. Minor or situational depressions are allowed.
- •Active elicit drug or alcohol abuse.
- •Serious co-morbid conditions as: heart failure, significant coronary heart disease, chronic obstructive pulmonary disease, renal insufficiency, poorly controlled diabetes, autoimmune disorders, and malignant diseases in the previous 5 years.
- •Immunosuppressive treatment including corticosteroids,
- •Untreated or uncontrolled or thyroid disease.
- •Solid transplant organ (renal, heart, or lung).
- •Pregnancy or unwillingness to practice double contraception or abstinence by the subject of childbearing potential or partner.
- •Subject objects to the study protocol.
- •Concurrent participation in any other clinical study within 30 days prior to enrollment.
研究组 & 干预措施
Combination therapy
干预措施: Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (Peg-IFN alpha-2a) and Ribavirin (Biological)
结局指标
主要结局
Change from baseline in physical examination
时间窗: Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
Body system screaning
Change from baseline in vital Signs
时间窗: Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
Heart Rate, Blood Presure, Respiratory Rate , Body temperature
Change from baseline in clinical laboratory parameters
时间窗: Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
Hematology, Blood Chemistry, Coagulation parameters, Urinalysis
Change from baseline in adverse events
时间窗: Twice on study first week , once a week during treatment initiation at weeks 2,3 ,4, later during treatment period once a month at weeks 8-48 and at weeks 60 and 72 follow up visits post treatment
All observed and or reported adverse events
次要结局
- HCV RNA level(at 4,12, 24, 48 and 72 weeks after treatment)