Phase 2B Dose Ranging Study of Locteron Plus Ribavirin to Treat HCV

The aim of SELECT-2 study was to compare the safety and efficacy of Locteron to PegIntron. SELECT-2 was a 72-week Phase 2b, multicenter, international trial of treatment-naïve genotype-1 chronic HCV subjects who were randomized 1:1:1:1 and dosed with one of three doses [640ug (n=29), 480ug (n=29), 320ug (n=28)] of q2week Locteron or weekly doses of 1.5ug/kg PEG2b (n=30). Subjects received these regimens in combination with weight-based ribavirin (800-1400 mg) for up to 48 weeks. Subjects and staff were blinded to Locteron dose for the first 12 weeks. Subjects without early virologic response by 12 weeks, and without viral negativity by 24 weeks, discontinued treatment for lack of efficacy. Adverse events including flu symptoms and depression, Beck Depression Inventory (BDI), Short Form-36, HCV RNA and safety labs were measured at standard intervals at clinic visits through Week 72. In addition, daily subject self-reports of flu symptoms using an electronic subject reporting tool (ePRO) were collected for the first 12 weeks.

Inclusion criteria

• Male and female subjects 18 through 69 years of age, inclusive
• Chronic hepatitis C genotype 1
• HCV ribonucleic acid (RNA) level > 10,000 IU/mL (by RT-PCR) at screening
• Creatine clearance ≥ 50 mL/min
• Neutrophil count > 1500 cells/mm3
• Platelet count > 90,000/mm3
• Hemoglobin > 12 g/dL for females and > 13 g/dL for males
• Female subjects of child-bearing potential agreeing to use dual methods for contraception
• Male subjects with female sexual partners agreeing to use effective birth control methods
• Negative serum pregnancy test for women of child-bearing potential • Compensated liver disease defined as INR < 1.5, conjugated bilirubin < 1.5 X ULN, serum albumin > 3.0 g/dL.

Exclusion criteria

• Prior antiviral treatment for hepatitis C
• Co-infection with HIV or hepatitis B virus
• Subjects with a body mass index (BMI) above 32 kg/m2
• Current or prior history of clinical hepatic decompensation
• Evidence of HCC
• Uncontrolled diabetes mellitus as evidenced by HbA1C ≥ 8.5% at screening
• Known hypersensitivity to interferon alfa or ribavirin
• Chronic liver disease other than HCV not limited to HBV, hemochromatosis, auto-immune hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease)
• Clinically significant hemoglobinopathy such as thalassemia major and sickle cell anemia
• History of moderate, severe or uncontrolled psychiatric disease including depression and prior suicide attempts
• History of immune-mediated disease
• Significant renal or neurological disease
• Severe degree (> GOLD stage III) of chronic pulmonary disease (COPD) or active, severe asthma
• Subjects with severe cardiac disease (e.g., heart failure, recent [i.e., within 6 months prior to first dosing] myocardial infarction, angina, serious arrhythmias, including prolonged QTc [> 450 mSec], uncontrolled hypertension)
• History of significant central nervous system (including CNS trauma) or seizure disorders
• Cancer within the last 5 years, or previous cancer with a high risk of recurrence, including metastatic breast cancer; non-melanoma skin cancer is not an exclusion criterion
• History of solid organ or bone marrow transplantation
• Clinical or laboratory evidence of uncontrolled thyroid disease, e.g., by thyroid stimulating hormone (TSH) level > 1.2 X upper limit of normal
• Clinically significant retinopathy; this needs to have been excluded by an eye exam performed by an ophthalmologist within the last 6 months prior to screening for subjects with hypertension or diabetes mellitus
• Drug abuse or alcohol consumption within the last 6 months which, in the opinion of the investigator, may affect study participation or outcome. Subjects in a supervised methadone treatment program on a stable regimen for > 6 months may be considered
• Taken any experimental agent within 12 weeks prior to screening
• More than 30 days of systemic immunosuppressive medication to include steroids in doses equivalent to or greater than 10 mg prednisone per day within 30 days prior to screening (inhaled corticosteroids are allowed)
• Nursing mother or male partner of pregnant female.