Safety and Efficacy of BIP48 (Peginterferon Alfa 2b 48kDa) Compared With Pegasys® (Peginterferon 2a 40kDa) for Treatment of Chronic Hepatitis C: Randomized, Multicentric Study With Blinded Analysis
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 740
- 试验地点
- 1
- 主要终点
- The rate of sustained virologic response - SVR - measured by PCR at 24 weeks after treatment.
研究概览
简要总结
The purpose of the study is to demonstrate the noninferiority of BIP48 (48 kDa peginterferon alfa-2b) compared to Pegasys ® (40 kDa peginterferon alfa-2a) associated with ribavirin, in naive patients with chronic hepatitis C.
详细描述
The study will be an open, multicenter, randomized, controlled phase II - III trial. Patients (n = 740) will be randomized (1:1) to receive BIP48 (peginterferon alfa-2b 48kDa) or Pegasys ® (peginterferon alfa-2a 40kDa) 180 micrograms ,subcutaneously,once a week,associated with ribavirin at a dose 1000-1250 mg, orally, daily. For genotype 1 treatment time will be 48 to 72 weeks and for genotypes 2 and 3, 24 to 48 weeks. The study's population will be naive patients, of both sex, between 18 and 70 years old, with chronic hepatitis C (HCV), genotypes 1, 2 or 3, from 18 to 25 Brazilian research centers. Diagnostic criteria will be as followed: positive anti-HCV and qualitative PCR, liver biopsy showing any degree of fibrosis and at least mild inflammatory activity, performed in the last 24 months. The interruption Criteria will be: no partial virological response at 12 weeks and positive quantitative PCR at week 24.The primary outcome will be the rate of sustained virologic response and the secondary endpoints will be the quality of life during treatment, frequency of adverse events and cost-effectiveness. As a substudy, will be performed a comparative assessment in 24 patients, evaluating viral kinetics, pharmacokinetics and pharmacodynamics of repeated doses of both alfapeginterferons .
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •anti-HCV positive;
- •viral load of HCV positive;
- •viral genotypes 1, 2 or 3;
- •the absence of previous treatment for chronic hepatitis C;
- •liver biopsy performed in the last 36 months classified by Metavir score as at least A1, with any degree of fibrosis ;
- •age from 18 to 70 years old;
- •hemoglobin greater than 11 g / dl;
- •platelet count higher than 75.000/mm3;
- •neutrophils higher than 1.500/mm3;
- •use of, at least two contraceptive methods during treatment and up to 36 weeks after the last dose of study medication (for male or female subjects in fertile age );
- •concordance and signing of the informed consent.
排除标准
- •decompensated cirrhosis (Child-Pugh score> 6);
- •history of bleeding gastroesophageal varices;
- •hemoglobinopathies;
- •hepatocellular carcinoma;
- •co-infection with HIV or HBV;
- •other coexisting chronic liver disease, as autoimmune hepatitis, Wilson disease, hemochromatosis, chronic obstructive cholestatic disease or autoimmune disease, alcoholic liver disease;
- •malignancies except basal cell carcinoma in situ or cervix carcinoma;
- •systemic autoimmune diseases, except compensated autoimmune thyroid diseases ;
- •uncontrolled seizures;
- •primary immunodeficiencies;
- •myelosuppression;
- •coagulation disorders;
- •thrombophilias;
- •thrombopathy ;
- •decompensated heart failure;
- •chronic renal failure;
- •diagnosis of other comorbidity that would compromise the subject's participation in the research study as judged by the investigator (eg, neuropsychiatric diseases, systemic infection or antibiotic use within 4 weeks, decompensated diabetes mellitus, ischemic heart disease, heart failure, respiratory or renal or uncontrolled hypertension);
- •prior organ transplantation, except cornea;
- •alcohol consumption exceeding 20g/day for women and 40g/dia for men during the past six months;
- •use of illicit drugs in the previous six months;
- •use of immunosuppressive agents during the previous six months;
- •pregnancy or lactation;
- •male research subjects whose sexual partner is pregnant;
- •previous treatment with IFN or ribavirin in the last 6 months prior to inclusion;
- •subjects with hypersensibility to IFN alpha and / or any of its components;
- •subjects with hypersensibility to ribavirin and / or any of its ingredients;
- •participation in another clinical study in the last 12 months
研究组 & 干预措施
Pegasys ®
Patients will receive Pegasys ® (peginterferon alfa-2a 40kDa) at a dose of 180 micrograms, subcutaneously, once a week, associated with ribavirin at a dose 1000-1250 mg,daily. For genotype 1 treatment time is 48 to 72 weeks and for genotypes 2 and 3, 24 weeks.
干预措施: BIP 48 (Peginterferon alfa 2b 48kDA) (Drug)
Pegasys ®
Patients will receive Pegasys ® (peginterferon alfa-2a 40kDa) at a dose of 180 micrograms, subcutaneously, once a week, associated with ribavirin at a dose 1000-1250 mg,daily. For genotype 1 treatment time is 48 to 72 weeks and for genotypes 2 and 3, 24 weeks.
干预措施: Peginterferon alfa 2a 40kDA (Drug)
BIP 48 (Peginterferon alfa 2b 48kDA)
Patients will receive BIP 48, 180 micrograms a week, SC, for the same period as Pegasys ®.
干预措施: BIP 48 (Peginterferon alfa 2b 48kDA) (Drug)
结局指标
主要结局
The rate of sustained virologic response - SVR - measured by PCR at 24 weeks after treatment.
时间窗: HCV PCR will be measured at 24 weeks after the end of therapy (week 48 for genotypes 2 and 3 and week 72 for genotype 1)
次要结局
- Frequency of adverse events(Clinical exam, blood tests and immunogenicity evaluation will be done twice monthly, in the first month, and then monthly until the end of treatment( week 24 for genotypes 2 and 3 and week 48 for genotype 1).)
- Virologic response at the end of treatment(Viral load will be measured at the end of treatment (week 24 for genotypes 2 and 3 and week 48 for genotype 1))