A Phase I Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Immunogenicity of Chiron Corporation's HCV E1E2/MF59 Vaccine Administered to Healthy HCV-Negative Adults
Overview
- Phase
- Phase 1
- Intervention
- HCV E1E2/MF59
- Conditions
- Hepatitis C
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Evaluate the safety, tolerability, and immunogenicity of HCV E1E2/MF59 vaccine when administered at 3 dose levels on a multi-dose schedule.
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
The purposes of this study are to evaluate the safety, tolerability, and effectiveness of a vaccine (the HCV E1/E2/MF59 vaccine) against hepatitis C (HCV). The vaccine will be given to 60 healthy adult volunteers (aged 18-45 years) and the study will compare the immune system (the body's protective response) response to the HCV E1/E2 vaccine given at different dosage levels: 4 micrograms, 20 micrograms, or 100 micrograms in MF59 adjuvant (substance that can improve vaccine effectiveness). The volunteers will be assigned randomly (by chance) to 1 of 4 different groups. Volunteers in each group will receive a shot of the vaccine or a placebo (shot with no medication). Participants will be involved in study related procedures for up to 71 weeks, which includes blood samples, recording symptoms on a diary card, and 4 vaccine or placebo injections.
Detailed Description
Hepatitis C virus (HCV) has emerged as a significant public health concern throughout the world. Its estimated prevalence in the US is 1.5 percent, or 2.7 million people with chronic infection. As many as 170 million people may have chronic HCV infection worldwide. The Centers for Disease control currently estimates that 40,000 HCV infections occur yearly in the US, with most current infection acquired through illegal injection drug use. It is estimated that 70 percent of those infected will develop chronic liver disease. The purpose of this study is to conduct a Phase I vaccine trial with a novel vaccine, HCV E1E2/MF59. The study objectives are to evaluate the safety, tolerability, and immunogenicity of HCV E1E2/MF59 vaccine administered to healthy adult subjects and to compare the immune response to HCV E1E2 vaccine given at 4, 20, or 100 mcg in MF59 adjuvant. Sixty healthy adults, aged 18-45, will be randomized to receive one of 3 different doses of vaccine or placebo. Each subject will receive vaccine at 0, 4, 24, and 48 weeks. Study procedures will include blood sample collections and questions regarding risk factors for acquiring HCV.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, hepatitis C virus (HCV) negative.
- •18-45 year old healthy adults. Insufficient data are available in adults to judge risk in children.
- •In good general health as determined by medical history, physical examination and the following screening labs:
- •Complete Blood Count (CBC): Total WBC (White Blood Cell): 3.5-14 thousand/microliter (MCL); Hemoglobin (Hgb): Men: 12.2-18 g/dl and Women: 10.5-17 g/dl.
- •Creatinine: Men: less than or equal to 1.4 mg/dl; Women: less than or equal to 1.2 mg/dl.
- •Glucose: 50 mg/dl to less than or equal to 109 mg/dl.
- •Alanine Aminotransferase (ALT): Men 2-60 units/litre (U/I): Women: 3-40 U/I.
- •Aspartate Aminotransferase (AST): Men: 2-50 U/I, Women 2-35 U/I.
- •Total bilirubin: Men: less than or equal to 1.5 mg/dl: Women: less than or equal to 1.3 mg/dl.
- •Urinalysis: negative or trace protein, negative glucose, less than or equal to 3 Red Blood Cells (RBC)/High Power Field (HPF) and less than or equal to 5WBC/HPF (in nonmenstruating females).
Exclusion Criteria
- •Diabetes.
- •Cancer other than squamous cell skin cancer which has been excised.
- •History of myocardial infarction or arrhythmia requiring hospitalization.
- •Syncope requiring hospitalization.
- •Unconsciousness other than a simple concussion.
- •Seizures other than febrile seizures as a child \<5 years of age.
- •Current liver disease (not including Gilbert's disease).
- •Autoimmune disease (does not include thyroid disease or vitiligo).
- •Splenectomy.
- •Uncontrolled hypertension \[blood pressure (BP) \>150/90; anti-hypertensive medications are acceptable).
Arms & Interventions
Group C: 100 mcg HCV E1E2/MF59 vaccine
Sixteen subjects receive four doses of 100 mcg HCV E1E2/MF59 vaccine (0.5 mL total volume) and 4 subjects receive placebo at 0, 4, 24, and 48 weeks.
Intervention: HCV E1E2/MF59
Group C: 100 mcg HCV E1E2/MF59 vaccine
Sixteen subjects receive four doses of 100 mcg HCV E1E2/MF59 vaccine (0.5 mL total volume) and 4 subjects receive placebo at 0, 4, 24, and 48 weeks.
Intervention: Placebo
Group B: 20 mcg HCV E1E2/MF59 vaccine
Sixteen subjects receive four doses of 20 mcg HCV E1E2/MF59 vaccine (0.5 mL total volume) and 4 subjects receive placebo at 0, 4, 24, and 48 weeks.
Intervention: HCV E1E2/MF59
Group B: 20 mcg HCV E1E2/MF59 vaccine
Sixteen subjects receive four doses of 20 mcg HCV E1E2/MF59 vaccine (0.5 mL total volume) and 4 subjects receive placebo at 0, 4, 24, and 48 weeks.
Intervention: Placebo
Group A: 4 mcg HCV E1E2/MF59 vaccine
Sixteen subjects receive four doses of 4 mcg HCV E1E2/MF59 vaccine (0.5 mL total volume) and 4 subjects receive placebo at 0, 4, 24, and 48 weeks.
Intervention: HCV E1E2/MF59
Group A: 4 mcg HCV E1E2/MF59 vaccine
Sixteen subjects receive four doses of 4 mcg HCV E1E2/MF59 vaccine (0.5 mL total volume) and 4 subjects receive placebo at 0, 4, 24, and 48 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Evaluate the safety, tolerability, and immunogenicity of HCV E1E2/MF59 vaccine when administered at 3 dose levels on a multi-dose schedule.
Time Frame: Duration of study.
Secondary Outcomes
- Compare the immune response to HCV E1E2 vaccine given at 4 mcg, 20 mcg, or 100 mcg in MF59 adjuvant.(Weeks 0, 2, 4, 6, 8, 24, 26, 50, 52 and 64.)