Placebo controlled, double-blind, multicenter study utilizing Standard of Care (SOC) 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 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 \< 2 log decline in HCV-RNA at Week 12 but \> 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.
The Principal Investigators, other site personnel, and patients will be blinded to the HCV-RNA results for the first 12 weeks of therapy.
At Week 12, the study treatment blind will be broken by the study's Interactive Web Randomization System (IWRS). However, the Principal Investigators, other investigative site personnel, patients, and Sponsor will remain blinded to treatment allocation until Week 24 (see below). The patients on the SOC + placebo arm will continue treatment as follows:
* Patients on SOC + placebo who do not achieve at least a 2 log decline in their HCV-RNA at Week 12 will be automatically rolled-over into the SOC + 15 mg CTS-1027 twice a day (BID) arm. The treatment duration for these patients will be 60 weeks (i.e., 12 weeks on SOC + placebo, followed by 48 weeks on SOC + 15 mg BID).
* Those patients on SOC + placebo who achieve ≥ 2 log decline at Week 12 will continue on SOC therapy until Week 48.
Patients in the SOC + CTS-1027 arms will continue with the same treatment regimen for the initial 24 weeks regardless of HCV-RNA changes.
At Week 24, the study blind will be formally broken. Patients will continue the study as follows:
* Patients in the SOC + CTS-1027 arms who achieve ≥ 2 log HCV-RNA decline by Week 24 will continue with the same treatment regimen they were assigned during the Double-Blind Phase for an additional 24 weeks.
* Patients in the SOC + CTS-1027 15 mg BID and the SOC + CTS-1027 30 mg BID arms who achieve a \<2 log HCV-RNA decline by Week 24 will escalate to the next higher dose of CTS-1027 for an additional 24 weeks.
* Patients in the SOC + CTS-1027 60 mg BID arm who do not achieve at least a 2 log HCV-RNA decline by Week 24 will be discontinued from the study.
All patients will be seen 4 and 12 weeks (Follow-Up Period) after the end of treatment. If a patient's HCV-RNA is undetectable at the end of treatment, he/she will be seen for an additional follow-up visit 24 weeks after the end of treatment.
