A Phase I, Randomized, Double-Blind, Dose-Ranging, Crossover Trial of HCV Vaccine (TG4040) in Patients With Chronic Hepatitis C to be Conducted in Two Parts

National Institute of Allergy and Infectious Diseases (NIAID)2 sites in 1 countryMarch 19, 2007

ConditionsHepatitis C

InterventionsPlacebo TG4040

DrugsPlacebo

Overview

Phase: Phase 1
Intervention: Placebo
Conditions: Hepatitis C
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Locations: 2
Primary Endpoint: Part I and Part II: safety including measures of reactogenicity, changes in blood counts and hepatic panel.
Status: Withdrawn
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of an investigational vaccine (TG4040) to prevent hepatitis C virus (HCV) infection. The primary goal of this study is to determine the safety of increasing doses of TG4040 versus placebo (an inactive substance) in subjects chronically infected with HCV. Approximately 85 patients, ages 18-65 years, with chronic HCV infection will be enrolled in this study at two sites, Saint Louis University and Cincinnati Children's Hospital. Volunteers will receive doses of TG4040 and placebo by injections into the thigh on different days, depending on which study group they belong to. Safety will be checked before doses are increased, and each participant will receive the study vaccine, TG4040, at some point during the study. Each subject will participate in the study for 8 months. This study may help produce a new vaccine that would improve control of HCV.

Detailed Description

The purpose of this study is to assess the safety, immunogenicity, and efficacy of the hepatitis C virus (HCV) vaccine, TG4040, in outpatients with chronic hepatitis C. The study will be conducted in two parts at two DMID Vaccine Treatment and Evaluation Unit (VTEU) Centers: Saint Louis University and Cincinnati Children's Hospital. Up to 85 subjects with chronic hepatitis C will receive the test vaccine via subcutaneous injection into the thigh. In Part I of this study, 18 subjects will be randomized to 1 of 3 groups. At the initial dosing time point, Group One will receive 10 to the 6th power particle-forming units (PFU) and Groups Two \& Three will receive saline placebo in 3 doses on Days 0, 7, and 14. After Safety Monitoring Committee (SMC) review, Group Two will receive a higher dose of TG4040 (10 to the 7th power PFU) and Groups One \& Three will receive saline placebo. After a further SMC review, Group Three will receive a higher dose of TG4040 (10 to the 8th power PFU) and Groups One \& Two will receive saline placebo. (Each subject will therefore be treated with one course of TG4040 and receive two courses of placebo). In Part II of this study, 60 subjects (30 non-responders or relapse subjects-Part IIa, and 30 treatment naïve, Part IIb) will be randomized into two groups to receive either 10 to the 8th power PFU (or the highest tolerated dose) of TG4040 or saline placebo at two dosing time points with a crossover design. (Each subject will therefore be vaccinated with the same dose of TG4040 and also receive a course of placebo.) Subjects enrolled in either Part I or Part II of the study will participate for 8 months. The primary objective for Part I of the study is to assess the safety of escalating doses of TG4040 versus placebo administered to non-responders or relapse subjects with chronic hepatitis C. The secondary objective for Part I of the study is to assess immunogenicity of escalating doses of TG4040 versus placebo administered to non-responders or relapse subjects with chronic hepatitis C. The primary safety objective for Part II of the study is to assess the safety of the dose of TG4040 selected from Part I versus placebo when administered to subjects with chronic hepatitis C, either non-responders or relapse subjects or treatment- naïve subjects. The primary efficacy objective for Part II of the study is to assess antiviral activity against HCV of TG4040 versus placebo in subjects with chronic hepatitis C, non-responders or relapse subjects or treatment-naïve subjects, assessed as a 1 log reduction in serum level of HCV RNA. The secondary objective for Part II of the study is to assess immunogenicity of TG4040 versus placebo in subjects with chronic hepatitis C, non-responders or relapse subjects or treatment-naïve subjects, and correlate this with reductions in serum levels of HCV RNA. For Part I, the primary outcome measures are related to safety and include measures of reactogenicity, changes in blood counts and hepatic panel. For Part II, the primary outcome variable is a change in serum levels of HCV RNA compared to baseline. A decrease in more than 1 log from baseline will be considered a significant effect. In addition to this, other primary outcome measures will also include safety and include measures of reactogenicity, changes in blood counts and hepatic panel. Secondary outcomes measures include those tests aimed at assessing immunogenicity of the vaccine candidate and include, but are not limited to, development of anti-HCV using standard commercial assays and research assays, developed of enhanced in vitro T cell reactivity when stimulated with HCV antigens.

Registry

clinicaltrials.gov

Start Date

March 19, 2007

End Date

September 2007

Last Updated

7 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

Inclusion Criteria

•Part I and Part II:
•Informed consent obtained and signed;
•Male or female patients, age 18-65 years old (inclusive)
•Female patients will be menopausal for at least 12 months, surgically sterile or agree not to become pregnant from the time of study enrollment until at least 28 days after the administration of vaccine or placebo. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized.
•If the volunteer is female, of childbearing potential, and sexually active, she agrees to use acceptable contraception. (Acceptable contraception methods are restricted to effective intrauterine devices (IUDs) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination and for the entire study period post-vaccination).
•Note: A woman is eligible if she is monogamous with a vasectomized male or abstinent, without the additional need for hormonal or barrier birth control methods upon review of a reproductive history.
•With chronic hepatitis C evidenced by:
•HCV RNA detectable in blood, and
•A liver biopsy compatible with chronic hepatitis C;
•Infected with HCV genotype 1;

Exclusion Criteria

•Part I and Part II:
•Co-infection with HBV (indicated by the presence of hepatitis B surface antigen (HBsAg) in serum) or HIV (anti-HIV in serum); patients with HIV positive sexual partner (by history) will not be included;
•Current HCV therapies through out the trial period
•Current alcohol abuse or drug addiction that in the opinion of the investigator may interfere with the subject's ability to comply with trial procedures.
•History of immunodeficiency
•Known or suspected impairment of immunologic function including moderate to severe kidney impairment
•Malignancy within the last 5 years, not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site or history of skin cancer at the vaccination site
•Significant cardiac disease, evidenced by:
•History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath on activity, or other heart conditions under the care of a physician
•Baseline ECG showing clinically significant abnormalities (e.g., all kinds of advanced atrioventricular block or intraventricular block with QRS \>120msec, QTc \>460 msec, or frequent premature atrial contractions, atrial fibrillation or other atrial arrhythmias, \> ventricular couplets or ST-T wave abnormalities diagnostic of myocardial ischemia or prior myocardial infarction. EKGs will be interpreted by an identified cardiologist at Saint Louis University prior to enrollment.

Time Frame: Solicited reactogenicity and AEs will be collected on the day of vaccination and daily for 6 days following vaccination. Unsolicited AEs will be collected throughout the study period.

Part II: change in serum levels of HCV RNA compared to baseline.

Time Frame: Part I: screening days -60 and -30, days 0, 14, 28 and month 6. Part II: screening days -60 and -30, days 0, 14, 28, 56, 90, and 180.

Secondary Outcomes

Tests to assess immunogenicity of the vaccine candidate and include, but are not limited to, development of anti-HCV using standard commercial assays and research assays, developed of enhanced in vitro T cell reactivity when stimulated with HCV antigens.(Part I: time points 1, 2, and 3-days 0, 7 and 14 post-vaccination and 2 months following the 3rd vaccination. Part II: time points 1 and 2-days 0, 7 and 14 post vaccination and 1, 2, 3 and 6 months following the 2nd vaccination.)