A Phase I/II Clinical Trial With Interferon Alfa 5 in Treatment-Experienced Patients With Genotype-1 Chronic Hepatitis C

Phase I/II, Multicenter, Randomized, Open,Active-Controlled, ClinicalTrial to Evaluate PK, PD, Safety and Tolerability Of Interferon Alfa 5, S.C. 3 Times Per Week, For 29 Days, To Treat-Experienced Pat. With Genotype-1 Chronic Hepatitis C

The general aim of this study is to determine if 3 MIU of IFN-α5 in monotherapy, and 1,5 MIU of IFN-α5 combined with 1,5 MIU of IFN- α2b, are safe dose levels as well as to investigate the antiviral efficacy and pharmacodynamics (PD) of such doses and drugs in treatment-experienced HCV patients with genotype 1 chronic infection, after 29 days of treatment. It is also intended to determine pharmacokinetics (PK) of the safe dose achieved of IFN-α5 in monotherapy.

Inclusion Criteria:

1. Patients aged ≥18 years old,
2. With chronic hepatitis C (CHC) infection diagnosed by seropositivity for anti-HCV antibodies or detectable HCV-RNA, at least 6 months prior to screening.
3. Patients with CHC infection of genotype 1 (1a, 1b or mixed 1a/1b)
4. Defined as relapsers: those CHC patients who had achieved virologic response (HCV-RNA non detectable) at any time during the standard care of treatment for CHC with IFN-α2 or PegIFN-α2 + ribavirin, and maintained it trough the end of treatment at week 48 weeks, but HCV-RNA detection occurs before 6 months post-treatment.
5. In whom liver cirrhosis has been ruled out through fibro-scan or liver biopsy within 24 months prior to study enrolment.
6. With a serum HCV viral load ≥ 100.000 IU/mL at screening
7. With alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) serum measurements at screening less than 5 times of their upper limits of normal (ULN)
8. With a body mass index (BMI) of at least 18 kg/m2, but not exceeding 36 kg/m2.
9. For female subjects with childbearing potential: use of a known highly effective method of birth control
10. For male subjects with partners of child bearing potential: use of appropriate contraceptive methods.
11. Is able to effectively communicate with the investigator and other testing center personnel.
12. Is able to participate and willing to give written informed consent and comply with the study restrictions.

Exclusion Criteria(principal):

1. Hepatitis C infection of genotype 2, 3 or 4 or any mixed genotype (1/2, 1/3 and 1/4).
2. A positive ELISA for HIV-1 or HIV-2.
3. Hepatitis B virus (HBV) infection based on the presence of HBsAg.
4. Hepatitis A virus (HAV) infection based on the presence of antiHAV-IgM. (AM 4)Criteria deleted
5. Decompensated liver disease, or history of decompensated liver disease.
6. History or other evidence of a medical condition associated with decompensated renal, immunologically mediated, chronic pulmonary, cardiac, thyroid, severe retinopathy, severe psychiatric, organ transplantation, cancer, seizure disorder or pancreatitis diseases.
7. An active or suspected malignancy or history of malignancy within the last five years.
8. Patients with a documented drug and alcohol addiction free history of at least 12 months who are, in the opinion of the investigator unlikely to relapse, may be enrolled in the study.
9. Positive results for drug abuse at screening.Occasional use of cannabis previously to randomization is not an exclusion criteria -under investigator team criteria-. The patient should be advised of abstinence during the trial (AM 6)
10. Haemoglobin <12.0g/dL for women, and <13.0g/dL for men at screening.
11. White blood cell count <2000 cells/mm3 at screening.
12. Absolute neutrophil count <1500 cells/mm3 at screening.
13. Platelet count <100.000 cells/mm3 at screening.
14. ALT and AST levels ≥ 5 xULN at screening.
15. Prothrombin time INR prolonged to 1.5xULN at screening.
16. TSH an T4 outside normal limits and not adequately controlled thyroid function at screening.
17. Poorly controlled diabetes mellitus as evidenced by HbA1c >7.5% at screening.
18. Alfa-fetoprotein value >100ng/mL at screening.
19. Total bilirubin >1.5xULN with ratio of direct/indirect >1, at screening unless predominantly conjugated and reflecting Gilbert's disease
20. Estimated creatinine clearance of 30 mL/minute or less at screening.
21. Women who are confirmed to be pregnant
22. People with known hypersensitivity to any ingredient of the investigational agents
23. Patients who are at risk of bleeding.
24. Haemoglobinopathy
25. Screening ECG QTc value ≥ 450ms and/or clinically significant ECG findings.
26. History of clinically significant drug allergies.
27. Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to anticipated dose administration.
28. Any chronic viral (including HSV), bacterial, mycobacterial, fungal, parasitic, or protozoal infection.
29. Requirement for chronic systemic corticosteroids.
30. Receiving systemic antivirals, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to enrollment.