Experimental AD4-H5-VTN Vaccine in Healthy Volunteers
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. 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. Tonsillar Participants will receive a booster dose of vaccine [SK1]at the 26-week visit and be seen for follow-up visits at Weeks 30 and 34. Household and intimate contacts will also be enrolled and monitored for Adenovirus and HAI antibodies.
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:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
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).
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. All subjects will be offered to receive a booster vaccination with a recombinant hemagglutinin influenza H5 vaccine after the 26-week visit and be seen for follow-up visits 4 and 8 weeks following booster immunization, with an additional telephone follow-up 6 months after boosting. Household and intimate contacts will also be enrolled and monitored for Adenovirus and HAI antibodies following Ad4-H5-Vtn administration only; household and intimate contacts will not be enrolled or monitored during the boost portion of the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01443936
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Mark Connors, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|