| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Influenza A Virus, H5N1 Subtype |
| Purpose: |
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Background:
- New vaccines against avian influenza, also known as "bird flu," are being developed and
require testing to determine if they are safe and effective and whether they have any side
effects. Researchers are interested in testing two experimental avian influenza vaccines to
see whether they are safe, if there are any side effects from the vaccines, and how the
body's immune response differs in response to different vaccination schedules. One vaccine
is an inactivated vaccine (made with killed or weakened influenza) and one is a DNA vaccine
that allows the body to use vaccine to make an immune system response to a specific part of
an avian influenza protein.
Objectives:
- To determine the safety and potential side effects of two experimental vaccines against
avian influenza.
- To evaluate whether the time between the two experimental vaccine injections affects
the immune response to the vaccine.
Eligibility:
- Healthy individuals between 18 and 60 years of age.
Design:
- Participants will be randomly divided (by chance) into six groups to receive two
injections of vaccine at different intervals. One group will receive only the
inactivated vaccine, while the other groups will receive the DNA vaccine followed by
the inactivated vaccine at different intervals (e.g., 4 weeks, 8 weeks, 12 weeks, 16
weeks or 24 weeks later).
- Participants will remain at the clinical center for at least 30 minutes after each
vaccination. A few days after each injection, participants will contact staff by
telephone or have a clinic visit. Participants will also be asked to complete a diary
card at home for 5 days to keep track of temperature changes, injection site skin
changes, and other effects.
- Four weeks after the first injection, participants will return for a clinic visit and
to provide blood samples for testing.
- Two weeks after the second injection, participants will return for a clinic visit and
provide blood samples (collected through apheresis) to provide information on immune
response to the vaccine.
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| Study summary: |
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An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity
of Prime-Boost Intervals with Monovalent Influenza Subunit Virion (H5N1) Vaccine,
A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant DNA
Plasmid (H5) Vaccine, VRC-AVIDNA036-00-VP (VRC, NIAID)
Study Design:
This is a Phase I, randomized, open-label study to evaluate the safety, tolerability, and
immunogenicity of prime-boost vaccination regimens against the influenza virus hemagglutinin
H5. One group will receive A/Indonesia/05/2005 (inactivated H5N1) vaccine as both prime and
boost, and the other groups will receive the VRC-AVIDNA036-00-VP (DNA) vaccine as prime with
inactivated H5N1 boost but with various boost intervals. The VRC 310 study will provide data
from different prime-boost schedules to identify whether homologous or heterologous
schedules result in a better antibody response as well as which interval of time between
vaccinations is associated with the best immune response. The hypothesis is that all of the
study regimens will be safe for human administration and will elicit antibody and T cell
responses against the H5 protein. The primary objectives are to evaluate the safety and
tolerability of the investigational vaccine regimens, at a dose of 4 mg for the DNA vaccine
and 90 microg for the inactivated H5N1, in healthy adults. Secondary and exploratory
objectives are related to the immunogenicity of the study vaccine regimens and
identification of an interval between prime and boost that has the highest frequency of
strong immune responses.
Product Description:
The inactivated H5N1 vaccine is monovalent subunit virion vaccine, A/Indonesia/05/2005 clade
2, manufactured by Sanofi Pasteur, Inc (Swiftwater, PA). Vaccine vials will be supplied at
90 microg/0.5mL. The VRC-AVIDNA036-00-VP vaccine was developed and manufactured by VRC,
NIAID and is composed of a single closed-circular DNA plasmid that encodes the H5 protein
with a CMV/R promoter. Vaccine vials will be supplied at 4 mg/mL. Each vaccination will be
administered intramuscularly (IM) in the deltoid muscle using needle and syringe for the
H5N1 vaccine and the Biojector 2000 Needle-Free Injection Management System (Biojector) for
the DNA vaccine.
Subjects:
A total of 60 healthy adults, ages 18-60 years will be enrolled.
Study Plan:
Subjects will be simultaneously randomized equally into one of 6 groups. Subjects and
clinicians will be blinded to group assignment until Day 0 following completion of the
enrollment. At the point of enrollment the randomly assigned regimen will become known to
subjects and clinicians. Subjects will receive two injections on the schedule shown in the
schema. The protocol requires 5 or 6 clinic visits, depending upon the group, and telephone
follow-up contact after the first study injection.
Study Duration:
Each participant will complete clinical follow up through 8 weeks after the second
vaccination. Duration of time on study will vary from 12 to 32 weeks depending upon the
Group. |
| Criteria: |
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- INCLUSION CRITERIA:
A subject must meet all of the following criteria:
18 to 60 years old.
Available for clinical follow-up for up to 32 weeks after enrollment.
Able to provide proof of identity to the satisfaction of the study clinician completing
the enrollment process.
Complete an Assessment of Understanding (AoU) questionnaire prior to enrollment and
verbalize understanding of all questions answered incorrectly.
Able and willing to complete the informed consent process.
Willing to donate blood for sample storage to be used for future research.
In good general health without clinically significant medical history.
Physical examination and laboratory results without clinically significant findings and a
Body Mass Index (BMI) < 40 within the 56 days prior to enrollment.
Laboratory Criteria within 56 days prior to enrollment:
Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to13.5 g/dL
for men
White blood cells (WBC) = 3,300-12,000 cells/mm(3)
Differential either within institutional normal range or accompanied by site physician
approval
Total lymphocyte count greater than or equal to 800 cells/mm3
Platelets = 125,000 - 500,000/mm(3)
Alanine aminotransferase (ALT) < 1.25 x upper limit of normal (ULN)
Serum creatinine less than or equal to 1 x ULN (less than or equal to1.3 mg/dL for
females; less than or equal to1.4 mg/dL for males)
Negative FDA-approved HIV blood test. [Note: Results of HIV enzyme-linked immunosorbent
assay (ELISA) will be documented, but a negative HIV polymerase chain reaction (PCR) test
result will be sufficient for eligibility screening of subjects with positive HIV ELISA
that is due to prior participation in an HIV vaccine study]
Women Specific:
Negative beta-HCG pregnancy test (urine or serum) for women presumed to be of reproductive
potential.
A female subject must meet one of the following criteria:
No reproductive potential because of menopause [one year without menses] or because of a
hysterectomy, bilateral oophorectomy, or tubal ligation,
OR
Agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week
28 of the study,
OR
Agrees to consistently practice contraception at least 21 days prior to enrollment and
through 8 weeks after last injection by one of the following methods:
- condoms, male or female, with or without a spermicide;
- diaphragm or cervical cap with spermicide;
- intrauterine device;
- contraceptive pills, patch, implant or any other FDA-approved contraceptive method;
- male partner has previously undergone a vasectomy.
EXCLUSION CRITERIA:
A subject will be excluded if one or more of the following conditions apply.
Women Specific:
Breast-feeding or planning to become pregnant during the first 28 weeks after enrollment
in the study.
Subject has received any of the following substances:
Systemic immunosuppressive medications or cytotoxic medications within the 12 weeks prior
to enrollment. [With the exception that a short course (duration of 10 days or less or a
single injection) of corticosteroids for a self-limited condition at least 2 weeks prior
to enrollment in this study will not exclude study participation.]
Blood products within 112 days (16 weeks) prior to HIV screening
Immunoglobulin within 56 days (8 weeks) prior to HIV screening
Live attenuated vaccines within 28 days (4 weeks) prior to initial study vaccine
administration
Investigational research agents within 28 days (4 weeks) prior to initial study vaccine
administration
Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy
treatment with antigen injections, within 14 days (2 weeks) of initial study vaccine
administration
Current anti-TB prophylaxis or therapy
Previous H5 avian influenza investigational vaccine.
Subject has a history of any of the following clinically significant conditions:
Contraindication to receiving an FDA approved current seasonal influenza vaccination
(e.g., egg allergy)
Serious reactions to vaccines that preclude receipt of study vaccinations as determined by
the investigator.
Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema.
Asthma that is unstable or required emergent care, urgent care, hospitalization or
intubation during the past two years or that requires the use of oral or intravenous
corticosteroids.
Diabetes mellitus (type I or II), with the exception of gestational diabetes.
Thyroid disease that is not well controlled.
Idiopathic urticaria within the past year
Hypertension that is not well controlled by medication or is more than 145/95 at
enrollment.
Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet
disorder requiring special precautions) or significant bruising or bleeding difficulties
with IM injections or blood draws.
Malignancy that is active or treated malignancy for which there is not reasonable
assurance of sustained cure or malignancy that is likely to recur during the period of the
study.
Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol
withdrawal more than 3 years ago, or 3) seizures that have not required treatment within
the last 3 years.
Asplenia, functional asplenia or any condition resulting in the absence or removal of the
spleen.
Allergic reaction to aminoglycoside antibiotics.
Guillain-Barr Syndrome.
Psychiatric condition that precludes compliance with the protocol; past or present
psychoses; past or present bipolar disorder; disorder requiring lithium; or within 5 years
prior to enrollment, a history of suicide plan or attempt.
Any medical, psychiatric, social condition, occupational reason or other responsibility
that, in the judgment of the investigator, is a contraindication to protocol participation
or impairs a volunteer's ability to give informed consent. |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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July 2, 2010 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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