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

Inclusion criteria

• Patients aged ≥18 years old,
• With chronic hepatitis C (CHC) infection diagnosed by seropositivity for anti-HCV antibodies or detectable HCV-RNA, at least 6 months prior to screening.
• Patients with CHC infection of genotype 1 (1a, 1b or mixed 1a/1b)
• 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.
• In whom liver cirrhosis has been ruled out through fibro-scan or liver biopsy within 24 months prior to study enrolment.
• With a serum HCV viral load ≥ 100.000 IU/mL at screening
• With alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) serum measurements at screening less than 5 times of their upper limits of normal (ULN)
• With a body mass index (BMI) of at least 18 kg/m2, but not exceeding 36 kg/m2.
• For female subjects with childbearing potential: use of a known highly effective method of birth control
• For male subjects with partners of child bearing potential: use of appropriate contraceptive methods.
• Is able to effectively communicate with the investigator and other testing center personnel.
• Is able to participate and willing to give written informed consent and comply with the study restrictions.

Exclusion criteria

(principal):

• Hepatitis C infection of genotype 2, 3 or 4 or any mixed genotype (1/2, 1/3 and 1/4).
• A positive ELISA for HIV-1 or HIV-2.
• Hepatitis B virus (HBV) infection based on the presence of HBsAg.
• Hepatitis A virus (HAV) infection based on the presence of antiHAV-IgM. (AM 4)Criteria deleted
• Decompensated liver disease, or history of decompensated liver disease.
• 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.
• An active or suspected malignancy or history of malignancy within the last five years.
• 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.
• 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)
• Haemoglobin <12.0g/dL for women, and <13.0g/dL for men at screening.
• White blood cell count <2000 cells/mm3 at screening.
• Absolute neutrophil count <1500 cells/mm3 at screening.
• Platelet count <100.000 cells/mm3 at screening.
• ALT and AST levels ≥ 5 xULN at screening.
• Prothrombin time INR prolonged to 1.5xULN at screening.
• TSH an T4 outside normal limits and not adequately controlled thyroid function at screening.
• Poorly controlled diabetes mellitus as evidenced by HbA1c >7.5% at screening.
• Alfa-fetoprotein value >100ng/mL at screening.
• Total bilirubin >1.5xULN with ratio of direct/indirect >1, at screening unless predominantly conjugated and reflecting Gilbert's disease
• Estimated creatinine clearance of 30 mL/minute or less at screening.
• Women who are confirmed to be pregnant
• People with known hypersensitivity to any ingredient of the investigational agents
• Patients who are at risk of bleeding.
• Haemoglobinopathy
• Screening ECG QTc value ≥ 450ms and/or clinically significant ECG findings.
• History of clinically significant drug allergies.
• Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to anticipated dose administration.
• Any chronic viral (including HSV), bacterial, mycobacterial, fungal, parasitic, or protozoal infection.
• Requirement for chronic systemic corticosteroids.
• Receiving systemic antivirals, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to enrollment.