Study Procedures
Here you will find additional information about the Herpevac Trial for
Women study design and procedures. If you are interested in volunteering
for the Herpevac Trial, the information below will give you a better
idea of what is involved. Also, keep in mind that the study staff at
the clinic site in your area can answer additional questions you may
have.
Which study participants receive the herpes
vaccine?
Once enrolled in the study, participants are "randomized" into one of
the study groups. (Randomization means being selected by chance much
like flipping a coin.) There is an equal chance of receiving the investigational
herpes vaccine or the investigational hepatitis A vaccine. To make a
fair test of the investigational herpes vaccine, neither the participant
nor the study health care provider will know which vaccine has been
administered until the study is over.
Is there a risk of getting herpes from the
vaccine itself?
Is there a risk of getting herpes from the vaccine itself? No. The investigational
herpes vaccine will not cause HSV infection. The herpes vaccine
formulation contains no live or infectious virus. It uses only a particular
section of a herpes virus protein that stimulates immune response.
How much time will be spent in the clinic?
The study will last 20 months, with a total of eight scheduled study
visits after the screening visit—at approximately months 0, 1, 2, 6,
7, 12, 16 and 20. The visits are not required to take place on an exact
day, and there is some flexibility built in to the study in order to
help with scheduling. Details are available from study sites.
Visits are of differing durations depending on what needs to be done
at the visit, and whether or not the study participant needs extra time
for counseling or discussion. The first two visits (the screening visit
and the first vaccine visit) are expected to take the longest.
The screening visit: During this visit, there is time for the
interested volunteer to review information and ask questions about the
study. Volunteers decide whether or not they want to provide consent
for screening, which includes being tested for herpes. They are given
a consent form to review and sign, and afterwards a blood sample is
taken to test for antibodies to herpes simplex type 1 and type 2.
Those who choose to participate are given a brochure that has information
about the screening test and about obtaining their test results by calling
the Herpevac Trial for Women test results hotline. If a volunteer tests
negative for both types of herpes simplex, she will be invited to return
to the study site to participate in the vaccine trial. For those who
test positive, the test results hotline provides information and counseling
regarding the meaning of a positive test for herpes type 1 and/or type
2.
At each visit: At each study visit, and during the months in
between visits via telephone, participants are reminded of ways to reduce
the risk of getting herpes, and they are taught how to recognize possible
herpes symptoms. (If a participant experiences symptoms, she will be
asked to come to the clinic for assessment.) They are also asked about
their general health including what medications they are taking.
Visit 1: Clinic staff review the risks, benefits and procedures
involved in being in the study. There are opportunities to ask questions.
Volunteer eligibility is again reviewed, including medical history.
The volunteer’s temperature is taken. If appropriate, volunteers are
given a physical examination to assess anything reported in the history
that should be examined further.
- If it is determined that a woman is eligible to join the study,
she is asked to sign a consent form to participate. After that, a
urine pregnancy test is performed. Blood tests are taken for antibodies
to the vaccine (this is a baseline test, as none are expected) and
for antibodies to naturally occurring herpes infection, again as a
pre-vaccine baseline. If the participant is not pregnant and has no
fever, she will receive the vaccine. Vaccine is administered in whichever
arm is not used for writing.
- After the vaccine is given, the volunteer is asked to stay for 30
minutes. During that time, she is asked to fill out, in private, a
questionnaire that asks some personal questions about sexual activity
and contraceptive use. The questionnaire will be kept confidential,
but the answers of all volunteers, compiled in aggregate, will be
used later to assess which factors increase the risk for herpes.
- Before going home, the participant is given a card (memory aid)
on which to write down any symptoms she may experience during the
7 day period post-vaccination that might be related to the vaccination.
The site will be in contact with the volunteer 7 to 10 days after
the vaccination to ask questions about possible side effects. Participants
don’t need to return the card to the site—it’s just to help them remember
details.
Visit 2: This is similar to the first visit, in that volunteers
are asked some questions about possible side effects or changes in their
health and receive another urine test to ensure that they have not become
pregnant. No blood is taken during visit 2. If the volunteer is not
pregnant and has no fever, she will receive the second dose of the vaccine,
wait 30 minutes, and go home with the memory aid. A follow-up call from
the study staff will be made 7 to 10 days after the vaccine is given.
Visit 3: This visit is for health questions and blood tests
only. The blood tests taken are to look for antibody response to the
vaccine and to see if the participant has acquired herpes simplex type
1 and/or 2. (Again, the vaccine cannot give someone herpes. If the blood
test shows new infection with herpes, the cause would have to have been
exposure to another person with herpes infection.) In addition, blood
samples will be stored for future tests of immune responses other than
antibodies to the vaccine.
- During this visit, participants will again be asked to fill out,
in private, the personal questionnaire about sexual activity and contraceptive
use.
- There are about 4 months between visit 3 (month 2) and visit 4 (month
6). A staff member from the study site will be in contact with volunteers
once during each month to inquire about their health.
Visit 4: This is similar to visit 2, and during this visit volunteers
receive the third and final dose of the vaccine following the last urine
pregnancy test. This visit is different from visit 2 only in that blood
is drawn to test for herpes antibodies. After receiving the vaccine,
participants are asked to wait the standard 30 minutes and will be sent
home with the memory aid to assist them with recalling possible side
effects. Again, the study staff will call between days 7-10 after the
visit.
Visit 5: For this visit volunteers have blood drawn to test
for herpes antibodies and extra blood is drawn and stored to use later
to test for immune responses other than antibodies to the study vaccine.
- There are about 5 months between visit 5 (month 7) and visit 6 (month
12). Between these visits, a staff member from the study site will
be in contact with volunteers once each month to inquire about their
health.
Visits 6-8: The last three visits involve more blood testing
for herpes antibodies (both in response to vaccine and to any possible
new infection with herpes) and the completion of the sexual activity
questionnaire at each visit.
What happens if a participant thinks she has
acquired herpes during the study?
Throughout the study, participants are advised about ways to reduce
their risks of acquiring genital herpes (e.g.., risk can be reduced
by using condoms, by avoiding casual sexual activity, and by noticing
typical herpes lesions in potential sexual partners). However, herpes
is common, and it is expected that some women who are participating
in the study will become infected with herpes by exposure to another
person. It is very important to know who gets infected and who doesn’t,
because this information is what is used to assess whether or not the
vaccine is effective.
During the study, volunteers are asked to look for any signs and/or
symptoms of herpes and record them on a diary card. If a woman has symptoms
she thinks may be caused by herpes, she is instructed to go to the clinic
as soon as possible—if feasible within 24 to 48 hours—for evaluation.
At this visit, the health care provider will examine the genital area,
including visualization of the cervix with a speculum, similar to a
pelvic exam by a gynecologist. During this exam, any sores/ulcers that
are present will be swabbed for a laboratory culture test. Even if there
are no sores noted, the area of symptoms will be swabbed for culture
because sometimes lesions of herpes can be difficult to see.
What if a woman is diagnosed with herpes during
the study?
While a diagnosis of herpes can be made from swabbing the area where
a person may be having symptoms, it is also possible for someone to
be diagnosed even when there are no symptoms of herpes at all. This
diagnosis of a herpes infection would occur based on the antibody tests
that are being done during the study. If this happens, the site staff
will discuss the meaning of these test results with the participant.
If a volunteer acquires genital herpes disease (herpes detected by
culture) or HSV-2 infection (herpes detected by blood test) during the
study, she will be invited to enter a separate viral shedding study,
which will start a few months after the diagnosis of herpes is made.
What kind of rights do the volunteer participants
have?
Currently, there is no FDA-approved vaccine for the prevention of herpes,
and no treatment can cure herpes. Participants are involved in this
study because they want to. Participation is voluntary, there are no
costs for being in this study, and all participants have a right to
ask questions about the study at any time. Volunteers also have the
right to withdraw from the study at any time, and they will be under
no further obligation for study procedures or vaccinations.
