A study of the safety of combining BIT225 with pegylated interferon and ribavirin, in patients with hepatitis C virus infection, including measurement of the concentration and distribution of BIT225 in the body and antiviral activity.

Exclusion Criteria37

• Patients who have received an investigational drug for HCV.
• Positive results for Hepatitis B (Hepatitis B surface antigen) and HIV antibody at Screening.
• History or presence of other evidence of a medical condition associated with chronic liver disease (e.g., chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, autoimmune hepatitis, Wilson’s disease, Gilbert’s syndrome, homozygote alpha1-antitrypsin deficiency, alcoholic liver disease, and toxin exposures).
• Bridging cirrhosis or cirrhosis confirmed on a biopsy obtained within the past 36 months as judged by a local pathologist. Note: patients with Metavir (or equivalent index) stage 3 fibrosis on a previous biopsy or patients with no previous biopsy will require an abdominal ultrasound within 6 months of first dose showing no evidence of cirrhosis
• History or signs of decompensated liver disease manifested by presence of Child-Pugh class B or C, ascites, variceal bleeding, or hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency
• History or other evidence of clinically significant renal disease.
• Pregnancy or breast feeding, male partners of pregnant females.
• Abnormal haematological and biochemical parameters within 60 days of Entry:
• a. Absolute neutrophil count <1000/mm3
• b. Haemoglobin <11 g/dL in females or 13 g/dL in males
• c. Platelet count <150,000/mm3
• d. International normalized ratio (INR) >1,5
• e. Total bilirubin within normal reference range
• f. Creatinine > 1.5 mg/dL
• Estimated creatinine clearance < 80 mL/minute at Screening. Value will be calculated using the Cockcroft-Gault formula.
• Screening ECG QTcB value >/= 450 ms.
• The consumption / administration of prohibited concomitant medication (prescribed, over-the-counter or complementary) at the time of the Screening visit. Any medication taken from 28 days prior to first dose through to the end of the participation in the study must be approved by the Biotron Medical Monitor in consultation with the Investigator.
• Active drug or alcohol use or dependence that, in the opionion of the site investigator, would interfere with adherence to study requirements.
• A positive result on urine screen for drugs of abuse and alcohol breath test at Screening or Day -1 which in the opinion of the Investigator should preclude them from participation in the study.
• History of severe psychiatric disease, which in the opinion of the Investigator should preclude them from participation in the study. Uncontrolled or active depression or other psychiatric disorder such as untreated Grade >/=3 psychiatric disorder, Grade >/=3 disorder not amenable to medical intervention, or any hospitalization within the past 52 weeks that in the opinion of the site investigator might preclude tolerability of study requirements.
• Any prior suicide attempt.
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, rheumatoid arthritis requiring more than intermittent non-steroidal anti-inflammatory medications for management, etc.) that may be exacerbated by interferon use.
• History or other evidence of chronic pulmonary disease associated with functional limitation.
• History of documented or presumed coronary artery disease or cardiovascular disease, clinically significant arrhythmia.
• History of a severe seizure disorder or current anticonvulsant use.
• History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha-fetoprotein >50 ng/mL.
• History of having received any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
• History of major organ transplantation with an existing functional graft.
• Active thyroid disease (use of thyroid hormone replacement therapy permitted by TSH or free T4 must be in normal range.) Any patient with a baseline increased risk for anaemia (e.g. thalassemia, spherocytosis, history of Gastrointestinal bleeding, etc) or for whom anaemia would be medically problematic.
• History or other evidence of severe retinopathy.
• Serious illness requiring systemic treatment and/or hospitalization within 24 weeks prior to entry; serious illness including malignancy, active coronary artery disease within 24 weeks prior to study entry; or other chronic medical conditions that may preclude completion of the protocol in the CRS investigator’s opinion. Such conditions may be discussed with the protocol chair/vice chair.
• Known allergy/sensitivity oh any hypersensitivity to components of study drug or its formulation.
• Heavy smokers (> 10 cigarettes per day) who are unable to refrain from smoking during the confinement periods in this trial.
• Difficulty abstaining from grapefruit and grapefruit containing products from 7 days prior to the first dose of investigational product until the end of the dosing period.
• Difficulty abstaining from high consumption of >2 cups coffee/tea/caffeine containing soft drinks per day.
• Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to anticipated dose administration.
• Current use of herbal medications or unwillingness to cease use during study participation.