Standard of Care (SOC) With or Without CTS-1027 in Hepatitis C (HCV) Null-Responders
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: CTS-1027; pegylated interferon; Ribavirin; Placebo
Intervention description: Supplied in 30mg, 10mg, or 5mg tablets (depending on dose arm) taken twice daily for up to 48 weeks.; 180 micrograms in 0.5 ml of solution subcutaneously (SQ), delivered in single use syringes administered once per week, for up to 48 weeks.; 200 mg capsules of ribavirn 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; Tablets identical in appearance to CTS-1027 containing inactive ingredients.
Placebo arm patients: Two tablets taken twice daily, for a total daily dose of four tablets.
30 mg CTS-1027 patients: One tablet taken twice daily, for a total daily dose of two tablets. One bottle of placebo is added to the 30mg kits in order to maintain the study blind (all patients recieve two-bottle kits of CTS-1027 and/or placebo).
Intervention MeSH terms: Interferons; Ribavirin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 114.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HCV; Null Responders

Summary:

      Placebo controlled, double-blind, multicenter study utilizing standard of care (SOC)
      treatment (ribavirin plus pegylated interferon) in combination with CTS-1027 in genotype 1
      chronic Hepatitis C (HCV) patients who were null-responders to previous SOC therapy(ies).

      Null-responders are defined as patients who failed to achieve a greater than 2 log drop in
      HCV-RNA (Hepatitis C Ribonucleic acid, also known as "viral load") levels after 12 weeks of
      treatment (know as an "early virologic response", or EVR) during previous SOC therapy.

      If, during previous SOC treatment, a patient had a less than 2 log decline in HCV-RNA at Week
      12 but greater than 2 log decline in HCV-RNA at any time from Week 12 to Week 24, that
      patient is not a null-responder, and is excluded from study participation. If, during
      previous SOC treatment, a Week 12 HCV-RNA was not obtained, the post Week 12 response must
      have been < 2 log decline (and still HCV-RNA positive) in order for the patient to be defined
      as a null-responder.

      Patients will be screened and have up to 4 weeks to qualify for study entry. During this
      screening period, clinical and laboratory tests will be performed. At Week 0/Day 1, patients
      will undergo centralized, stratified (based on ethnicity), randomization to one of four
      treatment arms: SOC + one of three doses of CTS-1027 or SOC + placebo. Study treatment will
      last 24, 48, or 60 weeks, based on each patient's response to study treatment. SOC + placebo
      patients who do not show a virologic response after 12 weeks of therapy will be rolled onto
      SOC + 15mg CTS-1027, while maintaining the study blind.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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 study

          2. 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, post Week 12 HCV-RNA response was < 2 log
                  decline

          3. Screening HCV-RNA viral load of > 5.0 log (i.e., >100,000 IU/mL)

          4. alpha-fetoprotein (AFP) less than or equal to 100 ng/mL

          5. Hemoglobin greater than or equal to 12 g/dL for women and greater than or equal to 13
             g/dL for men, hemoglobin A1c less than or equal to 7.5 %, platelet count greater than
             or equal to 90 x 10^9/L, and white blood cell count greater than or equal to 1.5 x
             10^9/L

          6. Thyroid Stimulating Hormone (TSH) within normal limits

          7. 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)

          8. 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 study.

        Exclusion Criteria:

          1. < 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)

          2. Decompensated or severe liver disease defined by one or more of the following
             criteria:

               -  Prothrombin time 4 seconds > control or INR (international normalized ratio) >
                  1.2

               -  Total bilirubin ≥ 1.5 mg/dL or direct bilirubin ≥ 1 mg/dL

               -  Serum albumin below normal limits

               -  aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 5 x upper
                  limit of normal (ULN) at screening

               -  Presence of ascites

          3. Hepatic encephalopathy

          4. Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or
             other imaging techniques)

          5. Clinically significant ocular findings such as retinopathy, cotton wool spots, optic
             nerve disorder, retinal hemorrhage, or other abnormality

          6. Known history or presence of human immunodeficiency virus (HIV) infection

          7. Co-infection with hepatitis B virus (HBV)

          8. If female: pregnant, lactating, or positive serum or urine pregnancy test

          9. Male partners of women who are currently pregnant

         10. Renal impairment (creatinine > 1.2 x ULN), serum creatinine clearance < 50 mL/min, or
             hepatorenal syndrome with ascites

         11. Hospitalization for liver disease within 60 days of screening

         12. History of alcohol abuse (> 50 g per day) within the past year

         13. History of severe psychiatric disease, especially depression, characterized by:

               -  Suicide attempt

               -  Hospitalization for psychiatric disease

               -  Period of disability as a result of psychiatric disease

         14. Prior exposure to CTS-1027

         15. Patients who qualify as a null-responder based on treatment(s) other than pegylated
             interferon and ribavirin

         16. History or presence of clinically concerning cardiac arrhythmias or prolongation of
             pre-dose corrected Q-T interval (QTc) of > 450 milliseconds

         17. History of or current autoimmune disease

         18. Diagnosis of or symptoms suggestive of fibromyalgia

         19. Currently on liver transplantation waiting list or recipient of any organ transplant

         20. 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 five or more years

         21. Exposure to any other investigational treatment for any aspect of disease associated
             with HCV during the past 6 months

         22. Exposure to any investigational drug or device within 30 days of dosing, or scheduled
             receipt of another investigational drug or device during the course of this study.