Randomized, Multicenter Study to Find Optimal Treatment Duration in Patients With Chronic Hepatitis C and Subtype 1 or 4 Depending on HCV RNA Level at Week 8 and Week 12
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 737
- 主要终点
- Percentage of Participants With Relapse Rate in Groups A and B by Genotype at the End of Follow-up (Part 1)
研究概览
简要总结
This study will compare the efficacy and safety of 2 different treatment durations of peginterferon alfa-2a (Pegasys) plus ribavirin in patients with CHC. The anticipated time on study treatment is 1-2 years, and the target sample size is greater than (>) 500 individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients with chronic hepatitis C and genotype 1 (1a or 1b) or genotype 4
- •Age between 18 and 70 years
- •Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
- •Present with at least one elevated serum alanine-aminotransferase (ALT) level higher than normal in the last 6 months before therapy start including the screening period
- •Positive HCV-RNA level in serum
- •Laboratory parameters (within 35 days prior to study start): -Hepatitis A anti - IgM negativity, HIV-Ab negativity, HBsAg negativity, Hemoglobin values > 12 g/dl in women or > 13 g/dl in men, Leukocyte count (WBC) > 3 000 /mcl, Platelets count > 100 000/mcl, Creatinine not 1.5 times higher than normal, normal TSH, normal uric acid with a maximum tolerance of 15 % in patients without history of gout
- •Liver biopsy findings within 6 months prior to study therapy consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis. Biopsies older than 1 year are eligible only after direct communication with the principal investigator
- •Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug. If there is no laboratory report existing, the physician should make an entry in the medical history that the pregnancy test was negative.
- •All fertile females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end. All fertile men with female partners must be using two forms of effective contraception during treatment and during the 7 months after treatment end.
- •Written informed consent obtained
排除标准
- •Any IFN and / or Pegylated IFN and ribavirin therapy at any previous time
- •Class B or C cirrhosis as coded by Child Pugh classification
- •Women with ongoing pregnancy or breast feeding
- •Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) 6 months prior to the first dose of study drug
- •Any investigational drug 6 weeks prior to the first dose of study drug
- •Drug addiction within 1 year prior to study start (patients participating in an official methadone program are eligible)
- •Diabetes mellitus in patients receiving an insulin therapy
- •Hemophiliac patients (due to the increased risk of requested liver biopsy)
- •History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
- •History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
- •History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease. Exception: if there is a current psychiatric report which certifies there is no contraindication to interferon therapy, patient may be included
- •History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis etc.)
- •History or other evidence of chronic pulmonary disease associated with functional limitation
- •History of a severe seizure disorder or current anticonvulsant use
- •History of severe cardiac disease and severe coronary heart disease within the last 6 months (angina pectoris, congestive heart failure, recent myocardial infarction, severe hypertension or significant arrhythmia). If there is clinical suspicion of coronary heart disease cardiologic workup of the patient prior to study entry is recommended.
- •History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
- •History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
- •History of major organ transplantation with an existing functional graft
- •Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
- •Inability or unwillingness to provide informed consent or abide by the requirements of the study
- •Additional exclusion criteria concerning ribavirin:
- •Male partners of women who are pregnant
- •Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, history of GI bleeding, etc) or for whom anemia would be medically problematic
- •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 would not be well-tolerated
研究组 & 干预措施
PEG-IFN 24 weeks
Participants will receive PEG-IFN (180 microgram [mcg]), subcutaneously (sc), once weekly for 24 weeks and Ribavirin 1000-1200 milligram per day (mg/day) (<75 kilogram (kg); >75 kg) for 24 weeks.
干预措施: Ribavirin (Drug)
PEG-IFN 24 weeks
Participants will receive PEG-IFN (180 microgram [mcg]), subcutaneously (sc), once weekly for 24 weeks and Ribavirin 1000-1200 milligram per day (mg/day) (<75 kilogram (kg); >75 kg) for 24 weeks.
干预措施: Peginterferon alfa-2a (Drug)
PEG-IFN 48 weeks
Participants will receive PEG-IFN (180 mcg), sc, once weekly for 48 weeks and Ribavirin 1000-1200 mg/day (<75kg; >75 kg) for 48 weeks.
干预措施: Peginterferon alfa-2a (Drug)
PEG-IFN 24/72 weeks
Participants will receive PEG-IFN (180 mcg), sc, once weekly and Ribavirin 1000-1200 mg/day (<75kg; >75 kg) till week 24; if patient is still HCV RNA positive. Treatment will be stopped if participant is HCV RNA negative at week 24 -treatment with PEG-IFN (180 mcg), sc, once weekly and Ribavirin 1000-1200 mg/day (<75kg; >75 kg) till week 72
干预措施: Peginterferon alfa-2a (Drug)
PEG-IFN 24/72 weeks
Participants will receive PEG-IFN (180 mcg), sc, once weekly and Ribavirin 1000-1200 mg/day (<75kg; >75 kg) till week 24; if patient is still HCV RNA positive. Treatment will be stopped if participant is HCV RNA negative at week 24 -treatment with PEG-IFN (180 mcg), sc, once weekly and Ribavirin 1000-1200 mg/day (<75kg; >75 kg) till week 72
干预措施: Ribavirin (Drug)
PEG-IFN 48 weeks
Participants will receive PEG-IFN (180 mcg), sc, once weekly for 48 weeks and Ribavirin 1000-1200 mg/day (<75kg; >75 kg) for 48 weeks.
干预措施: Ribavirin (Drug)
PEG-IFN 72 weeks
Participants will receive PEG-IFN (180 mcg), sc, once weekly for 72 weeks and Ribavirin 1000-1200 mg/day (<75 kg; > 75 kg) for 72 weeks.
干预措施: Ribavirin (Drug)
PEG-IFN 72 weeks
Participants will receive PEG-IFN (180 mcg), sc, once weekly for 72 weeks and Ribavirin 1000-1200 mg/day (<75 kg; > 75 kg) for 72 weeks.
干预措施: Peginterferon alfa-2a (Drug)
结局指标
主要结局
Percentage of Participants With Relapse Rate in Groups A and B by Genotype at the End of Follow-up (Part 1)
时间窗: Up to Week 96
Relapse rate (RR) was defined as the percentage of participants with non-detectable HCV RNA (\< 100 copies/ml) at the end of treatment and detectable HCV RNA at the end of follow-up. End of treatment was defined as Week 48 for Group A and Week 72 for Group B, respectively. The end of follow-up was defined as Week 72 for Group A and Week 96 for Group B, respectively. Relapse rate for treatment Groups A and B, stratified for genotype (Genotype I and Genotype IV) and Week 4 response (\< 600 units/milliliter \[U/ml\] and \>= 600 U/ml) is presented.
Percentage of Participants Achieving Sustained Virological Response in Groups A1, B1, and E by Genotype at the End of Follow-up (Part 2)
时间窗: Up to Week 96
The Sustained Virological Response (SVR) was defined as the percentage of participants in each group with non-detectable HCV RNA result at 24 weeks post completion of the treatment period (HCV RNA \< 15 IU/ml at Week 72 of Groups A1 and E, and at Week 96 of Group B1). Participants without a HCV RNA results at this time point were considered as non-responders. The end of follow-up was defined as Week 72 for Groups A1 and E, and Week 96 for Group B1. The SVR for treatment Groups A1 + B1 and E, stratified for genotype (Genotype I and Genotype IV) is presented.
次要结局
- Percentage of Participants With Virological Response Rate in Groups A, B, C, and D at the End of Treatment Period (Part 1)(Up to Week 72)
- Mean Fatigue Severity Scale Scores for Groups A and B Over Time (Part 1)(Baseline (Day 1), Week 24, Week 48 and Week 72, and Week 96)
- Percentage of Participants Achieving Sustained Virological Response in Groups A, B, C, and D at the End of Follow-up (Part 1)(Up to Week 96)
- Mean Short Form-36 Questionnaire Scores for Groups A and B Over Time (Part 1)(Baseline (Day 1), Week 24, Week 48, Week 72, and Week 96)
- Number of Participants With Fibrosis Grades 0 to 4 at Baseline (Part 1)(Baseline (Day 1))
- Number of Participants With Adverse Events and Serious Adverse Events (Part 1)(Up to Week 96)
- Percentage of Participants With Relapse Rates in Groups A1 and B1 at the End of Follow-up (Part 2)(Up to Week 96)
- Percentage of Participants With Virological Response Rates in Group A1, B1, C and D at the End of the Treatment Period (Part 2)(Up to Week 72)
- Percentage of Participants Achieving Sustained Virological Response in Groups C and D by Genotype at the End of Follow-up (Part 2)(Up to Week 96)
- Mean Short Form-36 Questionnaire Scores for Groups A1, B1, and C Over Time (Part 2)(Baseline (Day 1), Week 24, Week 48, Week 72, and Week 96)
- Mean Fatigue Severity Scale Scores for Groups A1, B1 and C Over Time (Part 2)(Baseline (Day 1), Week 24, Week 48 and Week 72, and Week 96)
- Number of Participants With Fibrosis Grades 0 to 4 at Baseline (Part 2)(Baseline (Day 1))
- Number of Participants With Adverse Events and Serious Adverse Events (Part 2)(Up to Week 96)