Standard of Care (SOC) With or Without CTS-1027 in Hepatitis C (HCV) Null-Responders

• Status: Terminated
• Trial end date: 2011-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Conatus Pharmaceuticals Inc.
• Treatments: Interferons; Ribavirin

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.