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Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
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Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00449124 |
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.
Condition | Intervention | Phase |
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Hepatitis C |
Drug: Placebo Biological: TG4040 |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator), Dose Comparison, Crossover Assignment, Safety/Efficacy Study |
Official Title: | 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 |
Estimated Enrollment: | 85 |
Estimated Study Completion Date: | September 2007 |
Estimated Primary Completion Date: | September 2007 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Part I-group 1: Experimental
Part I/Group 1: Cycle 1-TG4040 10^6 PFU days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14; Cycle 3-Placebo days 0, 7 and 14.
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Drug: Placebo
Injections of 0.5 mL of normal saline solution (0.9% NaCl).
Biological: TG4040
Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10^6 PFU, TG4040 10^7 PFU and TG4040 10^8 PFU.
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Part IIa-group 1: Experimental
Part IIa/Group 1: Cycle 1-TG4040 10^8 PFU days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14.
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Drug: Placebo
Injections of 0.5 mL of normal saline solution (0.9% NaCl).
Biological: TG4040
Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10^6 PFU, TG4040 10^7 PFU and TG4040 10^8 PFU.
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Part IIa-group 2: Experimental
Part IIa/Group 2: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-TG4040 10^8 PFU days 0, 7 and 14.
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Drug: Placebo
Injections of 0.5 mL of normal saline solution (0.9% NaCl).
Biological: TG4040
Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10^6 PFU, TG4040 10^7 PFU and TG4040 10^8 PFU.
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Part I-group 3: Experimental
Part I/Group 3: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14; Cycle 3-TG4040 10^8 PFU days 0, 7 and 14.
|
Drug: Placebo
Injections of 0.5 mL of normal saline solution (0.9% NaCl).
Biological: TG4040
Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10^6 PFU, TG4040 10^7 PFU and TG4040 10^8 PFU.
|
Part I-group 2: Experimental
Part I/Group 2: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-TG4040 10^7 PFU days 0, 7 and 14; Cycle 3-Placebo days 0, 7 and 14.
|
Drug: Placebo
Injections of 0.5 mL of normal saline solution (0.9% NaCl).
Biological: TG4040
Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10^6 PFU, TG4040 10^7 PFU and TG4040 10^8 PFU.
|
Part IIb-group 1: Experimental
Part IIb/Group 1: Cycle 1-TG4040 10^8 PFU days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14.
|
Drug: Placebo
Injections of 0.5 mL of normal saline solution (0.9% NaCl).
Biological: TG4040
Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10^6 PFU, TG4040 10^7 PFU and TG4040 10^8 PFU.
|
Part IIb-group 2: Experimental
Part IIa/Group 2: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-TG4040 10^8 PFU days 0, 7 and 14.
|
Drug: Placebo
Injections of 0.5 mL of normal saline solution (0.9% NaCl).
Biological: TG4040
Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10^6 PFU, TG4040 10^7 PFU and TG4040 10^8 PFU.
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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.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Part I and Part II:
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:
Patients participating in:
patients who have never received IFN-based treatment
Patients must have compensated liver disease, defined through use of the Child-Pugh scoring system with:
Exclusion Criteria:
Part I and Part II:
Significant cardiac disease, evidenced by:
History of any one of the following:
United States, Missouri | |
Saint Louis University | |
Saint Louis, Missouri, United States, 63110-0250 | |
United States, Ohio | |
Cincinnati Children's Hospital Medical Center | |
Cincinnati, Ohio, United States, 45229-3039 |
Responsible Party: | HHS/NIAID/DMID ( Robert Johnson ) |
Study ID Numbers: | 05-0061 |
Study First Received: | March 15, 2007 |
Last Updated: | September 11, 2008 |
ClinicalTrials.gov Identifier: | NCT00449124 History of Changes |
Health Authority: | United States: Federal Government; United States: Institutional Review Board; United States: Food and Drug Administration |
hepatitis C, vaccine, TG4040 |
Virus Diseases Hepatitis Liver Diseases Digestive System Diseases |
Hepatitis, Chronic Hepatitis, Viral, Human Hepatitis C Hepatitis C, Chronic |
Virus Diseases Hepatitis RNA Virus Infections Liver Diseases |
Digestive System Diseases Flaviviridae Infections Hepatitis, Viral, Human Hepatitis C |