OUTLINE OF PROTOCOL
002A
A PHASE I MULTICENTER,
RANDOMIZED TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF
VACCINIA-HIV ENVELOPE RECOMBINANT VACCINE (HIVAC-1e) IN COMBINATION
WITH SOLUBLE RECOMBINANT ENVELOPE VACCINE
Subjects: Healthy, HIV-1
uninfected adult volunteers without identifiable high-risk behavior
for HIV-1 infection, who have a history of smallpox vaccination >5
years prior to enrollment.
Schema:
|
Group
|
Treatment
|
Accrual*
|
Immunization Schedule
|
|
Day 0
|
Day 60
|
Day 180
|
Day 365
|
|
T1
|
VaxSyn/VaxSyn
|
10
|
V
|
V
|
V2
|
V2
|
|
T2
|
VaxSyn/HIVAC-1e
|
10
|
V
|
H
|
H
|
V2
|
|
T3
|
HIVAC-1e/VaxSyn
|
10
|
H
|
V
|
V2
|
V2
|
|
T4
|
HIVAC-1e/HIVAC-1e
|
5
|
H
|
H
|
V2
|
V2
|
|
Total
|
n = 35
|
|
|
|
|
V: VaxSyn 640 µg dose
V2: VaxSyn 640 •g (2-320 µg doses)
H: HIVAC-1e 2•1x109 pfu/ml
* Volunteers were randomized to one of the four groups
ACCRUAL, IMMUNIZATIONS, AND
FOLLOW-UP COMPLETED
Product Description: HIVAC-1e:
Vaccinia vector containing HIV-1 LAI rgp160 [Bristol
Myers-Squibb/Oncogen]
VaxSyn: Baculovirus/insect cell-derived HIV-1 LAI rgp160 in alum
[MicroGeneSys]
Time Period: First volunteer
entered on 05/06/91 and the last enrolled on 09/27/91; follow-up of
15 months.
Clinical Sites: Saint Louis
University, University of Washington, Vanderbilt
University
Study Chair: Lawrence Corey,
University of Washington
INCLUSION CRITERIA
- Age: >18 and
<60
- Sex: Male or Female, provided that conditions
are met which are designed to minimize the possibility that they
are pregnant or might become pregnant.
- Normal history and physical
examination
- Normal complete blood count and differential
defined as:
- Hematocrit >35% for women;
>39% for men
- White count >4000
cells/mm3 with normal differential
- Total lymphocyte count >800
cells/mm3
- T4 cells >500
cells/mm3
- Platelets (120,000-550,000)
- Normal urinalysis
- Normal ALT (<3.0 x upper normal limit) and
creatinine (0.1-1.6 mg/dl)
- Negative ELISA to HIV
- Negative Western Blot test for HIV (i.e., no
reactivity at gp160, gp120, gp41)
- Negative HIV p24 antigen test
- Normal cell mediated immune responses using
Merieux skin test
- History of smallpox vaccination >5 years
prior to study enrollment
- Normal immunoglobulin levels
EXCLUSION CRITERIA
- Subjects with identifiable high risk behavior
for HIV infection as determined by screening questions designed to
identify risk factors for HIV infection. Specific exclusions
include:
- Active intravenous drug use
- More than 2 sexual partners or sexual
contact with a high-risk partner in the preceding
6 months
- Blood or blood product transfusion within the
previous 6 months
- History of immunodeficiency, chronic illness,
or use of immunosuppressive medications in subjects or household
contact
- Lactating women
- Eczema, active or recent (within the past
year)
- Pregnant spouse or pregnant household
contact
- Household contact with child less than
12 months of age
- Household contact with person with
eczema
- Hypersensitivity to insects
- Prior receipt of an experimental HIV
vaccine
- Medical or psychiatric condition that makes it
unlikely the patient will comply with the protocol
STUDY GOALS
This Phase I vaccine trial of vaccinia-HIV
envelope recombinant vaccine and soluble recombinant gp160 vaccine
has as an objective the evaluation of differences in the immune
response between vaccinia naive and vaccinia immune subjects,
including the following:
- Frequency, time and titer of seroconversion to
HIV envelope proteins. This will include time to detection and
titer of HIV antibodies to gp160, 120 and 41 as detected by
Western blot and EIA antibodies.
- Development of anti-HIV neutralizing
antibody
- Stimulation of anti-HIV cell-mediated immunity
as measured by standard lymphoproliferative assays to HIV
antigens
- Development of CTL responses to HIV envelope
protein
- Adverse reactions (local, systemic or
immunologic), including assessment of severity of reactions
relative to the parent vaccine strain