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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.
Full description
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 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:
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.
Enrollment
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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 study
HCV genotype 1 infected null responders to prior therapy comprised of pegylated interferon and ribavirin (standard of care, SOC) defined as:
Screening HCV-RNA viral load of > 5.0 log (i.e., >100,000 IU/mL)
alpha-fetoprotein (AFP) less than or equal to 100 ng/mL
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
Thyroid Stimulating Hormone (TSH) within normal limits
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 study.
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:
Hepatic encephalopathy
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 > 1.2 x ULN), serum 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:
Prior exposure to CTS-1027
Patients who qualify as a null-responder based on treatment(s) other than pegylated interferon and ribavirin
History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose corrected Q-T interval (QTc) of > 450 milliseconds
History of or current autoimmune disease
Diagnosis of or symptoms suggestive of fibromyalgia
Currently on liver transplantation waiting list or recipient of any organ transplant
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
Exposure to any other investigational treatment for any aspect of disease associated with HCV during the past 6 months
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.
Primary purpose
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114 participants in 4 patient groups
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Data sourced from clinicaltrials.gov
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