A study of the safety of BIT225 in combination with pegylated interferon and ribavirin in patients with hepatitis C virus and human immunodeficiency virus co-infection, who are naive to treatment with pegylated interferon and ribavirin, and whose HIV is currently well controlled by standard antiretroviral therapy.

Exclusion Criteria38

• Patients who have received an investigational drug for HCV or HIV, HIV vaccine, immunomodulators (e.g. interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy, or other investigational therapy within 30 days prior to Day 0.
• Positive results for Hepatitis B (Hepatitis B surface antigen or HBV DNA in subjects with isolated HBcAb, defined as negative HBsAg, negative HBsAb and positive HBcAb (acute or chronic hepatitis B)) at Screening.
• Currently have any active AIDS defining illness (according to the CDC Surveillance Case Definition for HIV infection, AIDS-Defining Conditions, updated December 5, 2008).
• 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 liver 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 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.
• Abnormal haematological and biochemical parameters within 60 days of Entry:
• a. Absolute neutrophil count <1000/mm3
• b. Haemoglobin <12 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 outside of normal reference range
• f. Creatinine > 1.5 mg/dL
• Estimated creatinine clearance < 60 mL/minute at Screening, calculated using the Cockcroft-Gault formula.
• Screening ECG QTcB value >/= 450 ms.
• The consumption / administration of concomitant medication (prescribed, over-the-counter or complementary) at the time of the Screening visit listed as excluded medications. Any medication taken from 30 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 opinion of the site investigator, would interfere with adherence to study requirements.
• A positive result on urine screen for drugs of abuse at Screening which in the opinion of the Investigator should preclude them from participation in the study.
• History of severe psychiatric disease, or depression which in the opinion of the Investigator could be exacerbated by IFN therapy. 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 active 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.
• Evidence of an active or suspected cancer or a history of malignancy within 2 years of the study.
• History of having received any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to Day 0 or the expectation that such treatment will be needed at any time during the study.
• Active thyroid disease (use of thyroid hormone replacement therapy permitted but 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 until the participant either completes therapy or is clinically stable on therapy, in the opinion of the site Investigator, or at least 7 days prior to study entry.
• Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation.
• Unable to refrain from smoking during the PK evaluation periods of the trial.
• Difficulty abstaining from grapefruit, starfruit, and grapefruit containing products from 7 days prior to the first dose of investigational product until the end of the dosing period.
• 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.