Study of CTS-1027 in Combination With Pegylated Interferon and Ribavirin in Hepatitis C Virus (HCV) Null-Responders
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: CTS-1027; Pegylated interferon; Ribavirin
Intervention description: CTS-1027 supplied in 5 and 10 mg tablets, 15 mg taken twice daily, for up to 48 weeks; Pegylated interferon, 180 micrograms in 0.5 ml of solution injected subcutaneously (SQ) once per week, for up to 48 weeks. Packaged in single use syringes.; Ribavirin, 200 mg capsules taken in two divided daily doses totaling 1000 mg (5 capsules) for patients weighing 75 kg or less, or 1200 mg (6 capsules) for patients weighing more than 75 kg for up to 48 weeks.
Intervention MeSH terms: Interferons; Ribavirin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HCV; Null Responder

Summary:

      The purpose of this study is to determine if the combination treatment of CTS-1027, pegylated
      interferon and ribavirin can improve the response rates in HCV patients who did not
      previously respond to pegylated interferon and ribavirin therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients of minimum adult legal age (according to local laws for
             signing the informed consent document), able to provide written informed consent, and
             understand and comply with the requirements of the trial

          -  HCV genotype 1 infected null responders to prior therapy comprised of pegylated
             interferon and ribavirin (standard of care, SOC) defined as:

               -  Failure to achieve an early virologic response (< 2 log decline in HCV-RNA by
                  Week 12), or

               -  If Week 12 HCV-RNA was not obtained but Week 24 was obtained, Week 24 response
                  was < 2 log decline

          -  Alpha-fetoprotein (AFP) <= 50 ng/mL

          -  Hemoglobin ≥ 12 g/dL, platelet count ≥ 125 x 10^9/L, and white blood cell count ≥ 1.5
             x 10^9/L

          -  In the opinion of the Principal Investigator, the patient met the 80%/80%/80% rule
             during the previous pegylated interferon and ribavirin therapy (i.e., received at
             least 80% of the pegylated interferon and ribavirin doses, at least 80% of the dose
             size, for at least 80% of the treatment duration)

          -  Willingness to utilize two reliable forms of contraception (for both males and females
             of childbearing potential) from screening to at least six months after the completion
             of the trial.

        Exclusion Criteria:

          -  < 2 log decline in HCV-RNA at Week 12 but > 2 log decline at any time from Week 12 to
             Week 24 during prior therapy with pegylated interferon and ribavirin (prior standard
             of care therapy)

          -  Decompensated or severe liver disease defined by one or more of the following
             criteria:

               -  Prothrombin time 3 seconds > control

               -  Direct bilirubin ≥ 1.5 x ULN

               -  Serum albumin below normal limits

               -  AST or ALT > 7 x ULN at screening

          -  Evidence of portal hypertension including:

               -  Varices on esophagogastroduodenoscopy (EGD) with or without a history of
                  gastrointestinal bleeding; or

               -  Ascites

          -  Cirrhosis defined by one or both of the following criteria:

               -  Liver biopsy showing cirrhosis

               -  Other clinical signs and symptoms suggestive of cirrhosis

          -  Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or
             other imaging techniques)

          -  Clinically significant ocular findings such as retinopathy, cotton wool spots, optic
             nerve disorder, retinal hemorrhage, or other abnormality

          -  Known history or presence of human immunodeficiency virus (HIV) infection

          -  Co-infection with hepatitis B virus (HBV)

          -  If female: pregnant, lactating, or positive serum or urine pregnancy test

          -  Male partners of women who are currently pregnant

          -  Renal impairment (creatinine > 1.5 x ULN), creatinine clearance < 50 mL/min, or
             hepatorenal syndrome with ascites

          -  Hospitalization for liver disease within 60 days of screening

          -  History of alcohol abuse (> 50 g per day) within the past year

          -  History of severe psychiatric disease, especially depression, characterized by:

               -  Suicide attempt

               -  Hospitalization for psychiatric disease

               -  Period of disability as a result of psychiatric disease

          -  Prior exposure to CTS-1027

          -  Prior triple treatment comprised of pegylated interferon, ribavirin, and protease
             and/or polymerase inhibitors

          -  History or presence of clinically concerning cardiac arrhythmias or prolongation of
             pre-dose QTc interval of > 450 milliseconds

          -  Other concomitant disease or condition likely to significantly decrease life
             expectancy (e.g., moderate to severe congestive heart failure) or any malignancy other
             than curatively treated skin cancer (basal cell or squamous cell carcinomas), unless
             adequately treated or in complete remission for ten or more years

          -  Any patient who has received any investigational drug or device within 30 days of
             dosing, or who is scheduled to receive another investigational drug or device during
             the course of this trial.