A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of MVA-BN in a Dose Response Regimen Followed by Administration of Dryvax in Healthy Adult Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Smallpox
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- Adverse Events and side effects to the vaccines.
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The overall goals of this study are to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naive adults and to determine the optimum dose of MVA-BN to induce immune responses and attenuate Dryvax take reactions. Participants will include 90 healthy volunteers, ages 18-32 years. Participants will be randomly assigned to 1 of 6 study groups (groups A-F). Participants will be involved in study related procedures for up to 2 years. During this time, volunteers will return periodically for blood draws to check immune responses.
Detailed Description
The primary goal of this phase I trial is to expand the available data on the safety and immunogenicity of MVA-BN in vaccinia-naïve adults. The secondary goals of this vaccine trial are: to determine the optimum dose of MVA-BN, given twice, to induce an immune response and attenuate Dryvax® take reactions; and to compare the ability of 2 routes of administration of MVA-BN, subcutaneous and intramuscular, to induce an immune response at the highest tested dose. A total of 90 healthy adult volunteers ages 18-32 will participate in this study. The volunteers will be randomly assigned to 1 of 6 groups to be immunized with: MVA-BN (subcutaneously) at 1 of 3 dose levels and Dryvax® (per scarification); placebo (subcutaneously) and Dryvax® (per scarification); MVA-BN (subcutaneously) at the highest dose level and placebo scarification; or MVA-BN (intramuscularly) at the highest dose level and Dryvax® (per scarification). The study will last about 30 months. Each volunteer's participation will last 6 months for all treatment groups. Subjects randomized to treatment groups D and E will have follow-up for 2 years. During this time, volunteers will return periodically for blood draws to check immune responses. Subjects will require visits for dressing changes as needed post-Dryvax vaccination. Variables to be investigated include: adverse events and side effects to the vaccines, and immunogenicity testing including antibody and cellular responses to the vaccines.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Never received smallpox vaccination.
- •Read, signed and dated informed consent document.
- •Availability for follow-up for the planned duration of the study two years after first immunization.
- •Acceptable medical history by screening evaluation and limited physical examination.
- •For women, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination.
- •If the volunteer is female and of child bearing potential, she agrees to use acceptable contraception, and not become pregnant for at least 56 days after the last vaccination. A woman is considered of child bearing potential unless post-menopausal or surgically sterilized. \[Acceptable contraception methods are restricted to effective intrauterine devices (IUDs) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination.\] Women who are not sexually active must agree to use one of the acceptable contraception methods if they are of childbearing potential.
- •Negative ELISA for HIV.
- •ALT\<1.25 times institutional upper limit of normal.
- •Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
- •Negative urine glucose by dipstick or urinalysis.
Exclusion Criteria
- •History of immunodeficiency.
- •Typical vaccinia scar.
- •Known or suspected history of smallpox vaccination.
- •Military service prior to 1989 or after January
- •Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
- •Malignancy, including squamous cell skin cancer or basal cell skin cancer at vaccination site or history of skin cancer at the vaccination site.
- •Active autoimmune disease. Persons with vitiligo or thyroid disease on thyroid replacement are not excluded.
- •History of keloid formation.
- •History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor.
- •History of an immediate family member (father, mother, brother or sister) who has had onset of ischemic heart disease before age 50 years.
Outcomes
Primary Outcomes
Adverse Events and side effects to the vaccines.
Time Frame: Reactogenicity will be evaluated for a 2-week period post-vaccination at each time point and for the duration of study.
Secondary Outcomes
- Immunogenicity testing of antibody and cellular responses to the vaccines.(Visit days 0, 14, 28, 42, 56, 112, 140, 182, 365, and 730.)