BIP48 (Peginterferon Alfa 2b 48kDa) Compared With Pegasys® (Peginterferon 2a 40kDa) for Treatment of Chronic Hepatitis C

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

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.

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 .

Inclusion Criteria:

1. anti-HCV positive;
2. viral load of HCV positive;
3. viral genotypes 1, 2 or 3;
4. the absence of previous treatment for chronic hepatitis C;
5. liver biopsy performed in the last 36 months classified by Metavir score as at least A1, with any degree of fibrosis ;
6. age from 18 to 70 years old;
7. hemoglobin greater than 11 g / dl;
8. platelet count higher than 75.000/mm3;
9. neutrophils higher than 1.500/mm3;
10. 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 );
11. concordance and signing of the informed consent.

Exclusion Criteria:

1. decompensated cirrhosis (Child-Pugh score> 6);
2. history of bleeding gastroesophageal varices;
3. hemoglobinopathies;
4. hepatocellular carcinoma;
5. co-infection with HIV or HBV;
6. other coexisting chronic liver disease, as autoimmune hepatitis, Wilson disease, hemochromatosis, chronic obstructive cholestatic disease or autoimmune disease, alcoholic liver disease;
7. malignancies except basal cell carcinoma in situ or cervix carcinoma;
8. systemic autoimmune diseases, except compensated autoimmune thyroid diseases ;
9. uncontrolled seizures;
10. primary immunodeficiencies;
11. myelosuppression;
12. coagulation disorders;
13. thrombophilias;
14. thrombopathy ;
15. decompensated heart failure;
16. chronic renal failure;
17. 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);
18. prior organ transplantation, except cornea;
19. alcohol consumption exceeding 20g/day for women and 40g/dia for men during the past six months;
20. use of illicit drugs in the previous six months;
21. use of immunosuppressive agents during the previous six months;
22. pregnancy or lactation;
23. male research subjects whose sexual partner is pregnant;
24. previous treatment with IFN or ribavirin in the last 6 months prior to inclusion;
25. subjects with hypersensibility to IFN alpha and / or any of its components;
26. subjects with hypersensibility to ribavirin and / or any of its ingredients;
27. participation in another clinical study in the last 12 months