H5N1 Influenza Clinical Trial
Official title:
Phase 1 Study of Safety and Immunogenicity of Ad4-H5-VTN in Ad4 Seronegative and Seropositive 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.
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.
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. 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.
We will conduct an expansion H5N1 boost phase of this study, in which all vaccinees from the
initial phase of the study will be offered re-enrollment to receive a booster vaccination
with an FDA-approved H5N1 inactivated monovalent influenza vaccine. We will offer enrollment
in the expansion phase to all participants who received the Ad4-H5-Vtn vaccine in the initial
phase, regardless of whether they also received the recombinant hemagglutinin influenza H5
vaccine boost. We will also enroll individuals who have never received an H5 influenza
vaccine as controls. Participants will receive a single vaccination with the H5N1 vaccine and
be seen for follow-up visits 4 and 8 weeks later for immunogenicity evaluations.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01443663 -
Evaluating the Safety and Immune Response to an H5N1 Influenza Vaccine in People Who Have Previously Received an H5N1 or H7N3 Influenza Vaccine and in People Who Have Never Received a Live Attenuated Influenza Vaccine
|
Phase 1 | |
| Completed |
NCT01382329 -
H5N1 Vaccine Study in Japanese Adults
|
Phase 2/Phase 3 |