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

• Status: Completed
• Trial end date: 2016-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The study is a first in man, dose escalation study that will measure the safety and efficacy of TT-034 in the treatment of patients with chronic hepatitis C. The study is divided into 5 dose levels. Subjects will be given a single dose delivered by IV infusion. The subjects will be monitored and the data analyzed. After a set time, between 6 and 10 weeks depending on the dose level, the next set of subjects will be dosed. The study drug is a gene therapy treatment that produces molecules that destroy the Hepatitis C virus (HCV) in infected cells. Once the study drug is given, it cannot be withdrawn. Additionally, once an individual receives a dose, he or she will not be able to receive a second dose, but will remain eligible to receive most other HCV treatments.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tacere Therapeutics, Inc.

Criteria

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