An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders
An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders
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.
A subset of non-responders to standard of care treatments (pegylated interferon and ribavrin) is termed null responders. Null responders are the most treatment refractory population. Treatment for null responders is currently limited: retreatment with SOC results in approximately 5% sustained virologic response (SVR).
CTS-1027 may facilitate the activity of interferon by preventing MMP-induced cleavage and deactivation in both phases of clinical response to therapy. In addition, CTS-1027, like ribavirin, alone does not significantly affect viral replication, but both CTS-1027 and ribavirin are likely to impact response to therapy during the second and slower phase of the clinical response.
The potential of MMP inhibition to facilitate the action of interferon, together with ribavirin-driven up-regulation of interferon stimulated genes, has the potential to yield a potent host immune response in this highly resistant null-responder patient population. Again, since MMP inhibition is thought to target the second slower phase kinetics, the initial treatment duration in this trial will be 24 weeks.
This trial will evaluate the safety and efficacy of CTS-1027 combined with SOC in patients who did not previously respond to SOC therapy.
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:
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:
Evidence of portal hypertension including:
Cirrhosis defined by one or both of the following criteria:
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:
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.