Chiron Corp HCV E1/E2 Vaccine
Chiron Corp HCV E1/E2 Vaccine
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.
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.
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).

 -  Negative serum cryoglobulin

 -  Hepatitis B: negative Hepatitis B Surface Antigen (HBsAg) (using standard Food and
 Drug Administration FDA approved tests, e.g. Abbott or Organon).

 -  Hepatitis C: Anti-Hepatitis C Virus (HCV) negative and HCV Ribonucleic Acid (RNA)
 negative (using standard FDA approved tests, e.g. Abbott or Organon).

 -  HIV ELISA negative (using standard FDA approved tests, e.g. Abbott or Organon)
 (Written informed consent for HIV antibody testing will be obtained before obtaining
 the HIV sample.) Note: HIV vaccine volunteers who test positive by HIV ELISA and HIV
 western blot testing due to receipt of HIV vaccine may participate if they test
 negative by HIV DNA Polymerase Chain Reaction (PCR).

 -  Negative urine pregnancy test (females of child bearing potential) obtained at
 screening and at the day of each immunization.

 -  The ability to understand and sign a written informed consent document. Available for
 16 months after the first injection so that follow-up may be completed.

 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).

 -  Subjects with identifiable high-risk behavior for HCV infection as characterized by
 the following: injection drug use (IVDU) or cocaine snorting within the last year.

 -  Subject had a tattoo or body piercing within the past 6 months and/or is planning to
 acquire any tattoos or body piercing during the period of the study.

 -  Subjects with tattoos at the bilateral sites of needle insertion.

 -  Pregnant or lactating women. Women of child bearing potential must be using effective
 contraception for at least 30 days prior to initial immunization, unless for
 religious, social, or medical reasons they do not intend to have children and are
 practicing sexual abstinence. Subjects using birth control must agree to do so for the
 entire 64 week study period. Acceptable method of birth control is defined as hormonal
 contraceptives, intrauterine device (IUD), diaphragm with spermicide, condoms, a
 vasectomized partner or abstinence.

 -  Concomitant drug exclusion: corticosteroids (other than intranasal sprays or topical
 creams) or other known immunosuppressive drugs (such as chemotherapy for cancer); any
 experimental agent; any anti-tuberculosis medication, e.g., isoniazid (INH).

 -  Personnel engaged in the blinding of this study.

 -  Subjects who for any reason cannot adhere to the schedule of this protocol should not
 be enrolled in the study.

 -  Subjects who in the judgment of the investigator would not be good candidates due to
 medical, psychiatric, or social conditions which may interfere with or serve as a
 contradiction to adherence to the study protocol.

 -  Subjects with sex partners with known active Hepatitis B virus (HBV), HCV, or HIV
 infection.

 -  Currently abuses alcohol. Alcohol abuse is defined as requiring hospital admission for
 detoxification and therapy or alcohol use that has had a significant impact on
 personal relationships or ability to work productively.

 -  Not accessible by telephone or pager.

 -  Live attenuated immunization within 4 weeks of each vaccination.

 -  Inactivated immunization within 2 weeks of each vaccination.

 -  Febrile illness within 3 days of study entry based on verbal report by the subject.