Experimental AD4-H5-VTN Vaccine in Healthy Volunteers
- Adenoviruses typically cause cold or pink eye symptoms. These viruses may be used in vaccines to help stimulate an immune system response. Researchers want to test an adenovirus vaccine called the AD4-H5-VTN to see if it produces a strong enough immune response. AD4-H5-VTN may then be used as part of vaccines to prevent diseases such as malaria or HIV. However, because the vaccine may cause cold symptoms, the people who receive the vaccine and members of their household must take part in the study.
- To test the safety and effectiveness of the AD4-H5-VTN vaccine.
- Healthy volunteers between 18 and 45 years of age.
- Household members or intimate contacts of the volunteers between 18 and 65 years of age. People in households with young children or persons with immune system problems will not be allowed on this study.
- Participants will be screened with a physical exam and medical history. They will have blood and urine tests. They will also answer questions about their household and close contacts.
- Participants will receive the study vaccine in one of three forms: a pill, a nasal spray, or a throat spray given in the back of the mouth on the tonsils. Those who have the nasal or tonsil vaccine must stay in the hospital for 7 days after receiving it.
- Participants will keep diaries to record any symptoms or side effects of the vaccine.
- Followup study visits will be required weekly for the first month, and at 8 weeks, 6 months, and 1 year after taking the vaccine.
- Participants must not have vaccines (including seasonal flu vaccine) or allergy shots for 30 days before and after receiving the study vaccine....
Biological: Ad4-H5-VTN vaccination-tonsillar route
Biological: Ad4-H5-vaccination-oral route
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Study of Safety and Immunogenicity of Ad4-H5-VTN in Ad4 Seronegative and Seropositive Volunteers|
- Safety: evaluate local toxicity & amp; systemic reactions to vaccination. Severe reactions to vaccine (i.e. lower respiratory or GI tract disease) or systemic symptoms related to vaccine.
- Immunogenicity: Data collected for: H5-specific antibody, mucosal humoral, & amp; cellular immune response; vaccine virus shedding & amp; genetic stability; transmission of virus to household/intimate contacts.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||September 2014|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Biological: Ad4-H5-VTN vaccination-tonsillar route
This is a Phase 1 randomized, single center, dose-escalation study designed to evaluate the safety and immunogenicity of live, replication competent recombinant Adenovirus type 4-H5N1Influenza Vietnam 1194 Hemagglutinin (HA) (Ad4-H5-Vtn). Determining the optimal route and dose for this recombinant platform will greatly accelerate investigations of this vector as an influenza vaccine and an HIV vaccine platform.
Intranasal and tonsillar administration of the vaccine will be separately assessed. The oral enteric-coated capsule will also be assessed in 10 outpatients using similar blood sampling for comparison. The Ad4-H5-Vtn orally administered as enteric-coated capsules has already been evaluated in an ascending dose Phase 1 study, in dosages as high as 10(11) viral particles (vp).
The primary goal of this study is to evaluate safety of ascending dosages of the Ad4-H5-Vtn vaccine following intranasal and tonsillar administration. A dosage or dosages will be selected to further evaluate the humoral, cellular, and mucosal immune responses against both the vector and the inserted gene. The Ad4-H5-Vtn will be initiated at 10(3) vp. Once safety is established at the initial dose, a second round of testing will begin at the next ten-fold higher dose. The Ad4-H5-Vtn vaccine will be assessed in three participants at each dosage level. The maximum viral dose administered by the tonsillar route will be 10(8) vp.
In addition to clinical and laboratory monitoring of safety, the principal assessments will be shedding of the Ad4-H5-Vtn virus in rectal, cervicovaginal, throat, and nasal swabs, and assessment of the antibody (mucosal and systemic) response to the HA and to the Ad4 virus. Participants receiving the vaccination by the tonsillar route will remain in the NIH Special Clinical Studies Unit until they have 2 consecutive negative nasal washes or 7 days have elapsed since vaccination, whichever occurs first; they may remain on the unit longer if medically necessary. When safety has been confirmed in all three participants at a given dosage level, the next higher dose group is enrolled. If one grade 3 or greater toxicity (or pre-specified Grade 2 toxicity, see Section 3.4) attributable to the vaccine is observed, the group will be expanded at that dose. If a second attributable grade 3 or greater toxicity (or pre-specified Grade 2 toxicity, see Section 3.4) is observed, the dose will be reduced one level and the group will be expanded. Up to 25 Ad4-seronegative individuals will be enrolled at the maximum tolerated dose to fully evaluate safety and immunogenicity in the protocol.
All participants will be followed for 28 days following immunization, and again at 8 and 26 weeks to evaluate any long-term toxicity and persistence of immunity. Household and intimate contacts will also be enrolled and monitored for Adenovirus and HAI antibodies.
|Contact: April Poole, R.N.||(301) firstname.lastname@example.org|
|Contact: Mark Connors, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Mark Connors, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|