Safety and Efficacy Study of Single Doses of TT-034 in Patients With Chronic Hepatitis C

This is an interventional treatment trial for Hepatitis C focused on measuring Genotype 1, Chronic Hepatitis C, CHC, HCV, Hepatitis, RNAi, shRNA, ddRNAi, AAV8, AAV, Adeno-associated virus, Adeno-associated viral vectors Read More

Inclusion Criteria:

Subjects must a history of chronic HCV infection defined as documented HCV genotype 1 infection for at least 6 months.

• Subjects must have:

  1. Documented failure to respond to prior treatment or relapse with a combination of peg-interferon (peg-IFN), ribavirin (RBV), and either boceprevir or telaprevir, OR a combination of peg-IFN and ribavirin or
  2. Subject is ineligible or unwilling to receive a combination of peg-IFN, RBV, and either boceprevir or telaprevir.

• Female subjects have to be of non-childbearing potential, defined as meeting any of the following criteria:

  1. Female subjects over the age 60.
  2. Female subjects aged 45-60 years old must be amenorrhoeic for at least 2 years and must have serum follicle stimulating hormone (FSH) levels > 30 IU/L.
  3. Female subjects with hysterectomy or bilateral oophorectomy. All female subjects must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline.
• Male subjects and their partners must be willing to comply with the following requirements to use 2 methods of effective contraception: Male subjects with a vasectomy must use a condom. Without a vasectomy, male subjects must use a condom. The female must be sterile or willing to use an additional form of contraception.
• Baseline HCV RNA level of > 100,000 IU/mL and:
• No evidence of cirrhosis at Screening
• At least 3 months since prior therapy for HCV
• A willingness to enroll in a 5 year follow-up safety study

Exclusion Criteria:

• Body mass index < 18.5 or > 30
• Total body weight > 80 KG
• Female subjects of childbearing potential (including females with tubal ligation) or women who are pregnant or nursing
• Male subjects who are unwilling to provide the required semen samples
• Presence of nAb levels to AAV8 that abrogate AAV8 transduction
• Severe Liver disease
• Hepatocellular carcinoma (HCC) or suspicion of HCC
• Coronary artery disease
• Platelet count of < 150 x 109/L or Creatinine ≥ 1.5 mg/dL at Screening
• Hypertension with systolic blood pressure consistently ≥ 130 mmHg or diastolic blood pressure consistently ≥ 90 mmHg
• Screening examinations indicative of possible occult malignancy unless cancer has been excluded
• Family history of colon cancer in any first-degree relative unless ruled out by colonoscopy
• Positive for human immunodeficiency virus 1 (HIV1) or HIV2 antibody
• Co-infection with hepatitis B virus
• History of autoimmune disease
• Renal impairment
• Hospitalization for liver disease within 60 days of Screening
• Use of drugs of abuse in the prior 3 months
• Other concomitant disease or condition likely to significantly decrease life expectancy or cancer
• Treatment with an investigational drug within 6 months preceding the first dose of trial medication
• Received an AAV vector previously or any other gene transfer agent in the previous 6 months
• History of cardiac abnormalities, as assessed at the Screening Visit
• Twelve-lead ECG demonstrating QTcB > 465 ms at Screening
• Chronic hepatic diseases
• Evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, neurologic, or allergic diseases.
• Evidence of autoimmune disease or pre-existing autoimmune or antibody-mediated diseases
• Use of immunosuppressive medications within 6 months before the entry into this study, except for inhaled or topical corticosteroids