Status and phase
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About
Background:
Researchers want see if three new HIV (human immunodeficiency virus) vaccines are safe. Two vaccines are carried by live adenoviruses, which are natural and typically cause cold symptoms or an eye infection. Researchers want to see if all the vaccines help fight HIV and if the adenoviruses are contagious.
Objectives:
To test the safety and effects of three new HIV vaccines.
Eligibility:
Healthy adults 18 49 years old (vaccinees)
Their household and intimate contacts 18 65 years old
Design:
Vaccinees will be screened with:
Physical exam
Medical history
Blood and urine tests
Questions about HIV risk
Vaccinees will learn how to prevent spreading the viruses and about required contraception during the study.
Vaccinees will get consent forms for their household and intimate contacts. All contacts must be age 18 65. All intimate contacts must sign a consent form. Contacts will have 4 visits over 8 months for blood tests and a physical exam.
All applicable participants will have a pregnancy test at every visit.
Vaccinees will have about 9 visits over 12 months. They will repeat screening tests and get:
1 of the 2 adenovirus vaccines sprayed in the nose at 2 visits
The booster vaccine by needle in an arm at 1 visit
Nasal swabs taken at some visits
Vaccinees will note their temperature and symptoms for at least 1 4 weeks after each vaccine.
Vaccinees may choose to have:
Leukapheresis. Blood will be removed by needle in a vein in one arm. A machine will remove white blood cells. The rest of the blood will be returned into the other arm.
Small pieces of the tonsil removed
Sponsoring Institute: National Institute of Allergy and Infectious Diseases
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Full description
This is a Phase 1 study to evaluate the immunogenicity and safety of adenovirus serotype 4 (Ad4)-based HIV vaccines when administered via the intranasal route to healthy human volunteers. It is hypothesized that the vaccines will be safe for human administration and will elicit immune responses to the HIV components. All study activities will be carried out at the NIH.
Each study vaccinee will receive 5x10^8 viral particles of either Ad4-Env150KN or Ad4-Env145NFL, administered as an intranasal spray at months 0 and 2. An intramuscular protein booster vaccination with the heterologous soluble trimeric protein VRC-HIVRGP096-00-VP (Trimer 4571) with alum will be administered to all vaccinees at month 6. Specimens to evaluate immunogenicity will be taken at baseline and at specified time points through month 12. The HIV-specific immune responses will be assessed by cellular immune function assays (intracellular cytokine analysis, flow cytometry-based killing assays), as well as measures of humoral immunity (enzyme-linked immunosorbent assay [ELISA] and neutralization assays).
The overall goal will be to compare the safety and immunogenicity of the Ad-HIV vaccine regimens. Participants who have previously received another HIV vaccine and/or are Ad4 seropositive will be enrolled into an exploratory arm to be analyzed separately.
Household contacts willing to participate and all intimate contacts (current and/or those expected within the first 4 weeks after vaccination) will also be enrolled and monitored for transmission of the vaccine virus by serology.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
All participants (vaccinees, household contacts, and intimate contacts) must meet all of the following criteria:
The following inclusion criteria apply to vaccinees and intimate contacts, but not to household contacts:
In good general health without clinically significant medical history.
Assessed as low risk for HIV infection by agreeing to discuss HIV infection risks with the study clinicians, agreeing to HIV risk reduction counseling, and agreeing to avoid behavior associated with high risk of HIV exposure through the last required clinic visit in the protocol schedule.
Negative beta-HCG pregnancy test for females presumed to be of reproductive potential.
Female vaccinees and male intimate contacts must meet one of the following criteria:
-The female vaccinee has no reproductive potential because of menopause (1 year without menses) or because of a hysterectomy, bilateral oophorectomy, medically-documented ovarian failure, or tubal ligation.
or
-The female vaccinee and her male intimate contact(s) agree to be heterosexually inactive or consistently practice contraception at least 21 days prior to each vaccination through 28 days following each vaccination. Acceptable methods of contraception include any of
the following:
Male vaccinees and female intimate contacts must agree to consistently practice abstinence or effective birth control (described above) and for 28 days following each vaccination.
The following inclusion criteria apply only to vaccinees and not to household or intimate contacts:
Willing to receive HIV test results and abide by NIH guidelines for partner notification of positive HIV results.
Physical examination and laboratory results without clinically significant findings within the 8 weeks prior to enrollment.
Willing to avoid other investigational and/or HIV vaccinations, other than the study agent, from screening through the end-of-study visit.
Safety laboratory criteria within 8 weeks prior to enrollment:
Hematologic:
Renal: Blood urea nitrogen (BUN) <23 mg/dL; creatinine within normal limits for the NIH CC (females: 0.51-0.95 mg/dL; males: 0.67-1.17 mg/dL).
Hepatic: Serum direct bilirubin within normal limits for the NIH CC (0.0 to 0.3 mg/dL).
Metabolic: Alanine aminotransferase (ALT) <2 times upper limit of normal range (females: <66 U/L; males: <82 U/L).
Additional laboratory criteria:
Willing to follow precautions for preventing the spread of adenovirus in the community.
Males must agree not to donate sperm for 28 days following each study vaccination.
EXCLUSION CRITERIA:
A participant (vaccinees, household contacts, and intimate contacts) will be excluded if they have the following:
The following exclusion criteria apply to vaccinees and intimate contacts, but not to household contacts:
History of any prior disease or therapy which would affect immune or pulmonary function.
Prior malignancy, except curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
History of radiation therapy or cytotoxic/cancer chemotherapy.
History of uncontrolled diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c <= 8% within the last 6 months) or a history of isolated gestational diabetes are not exclusionary. Enrollment of individuals with Type 2 DM that is well controlled on hypoglycemic agent(s) may be considered on a case-by-case basis, provided that the HgbA1c is <= 8% within the last 6 months
Immunodeficiency or autoimmune disease.
Acute infection or a recent history (within 6 months) of chronic infection suggestive of immunodeficiency.
Taking any glucocorticoids or other immunosuppressive medications.
Asthma is excluded if the participant has ANY of the following:
Other chronic respiratory disorders including emphysema, interstitial lung disease, pulmonary hypertension, recurrent pneumonia, or recent or ongoing respiratory tract infection. If a respiratory disorder is transient, the study vaccination may be deferred without excluding the participant.
Female of childbearing potential who is breast-feeding or planning pregnancy during the period from enrollment through 28 days following the last study vaccination.
The following exclusion criteria apply only to vaccinees and not to household or intimate contacts:
Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with or serve as a contraindication to receipt of live virus vaccine, protocol adherence, or a participant s ability to give informed consent.
Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to enrollment.
Individuals that live in the same house or apartment with any of the following will be excluded:
Healthcare worker who has direct contact with immunodeficient, unstable, elderly, or pediatric patients.
Individuals caring for children <18 years of age or elderly individuals.
Receipt of any of the following:
Active hepatitis B or C infection (i.e., hepatitis B or C positive serology with the presence of virus antigen or DNA). Ongoing viral replication will be confirmed by a hepatitis B antigen test or hepatitis C viral load.
History of Guillain-Barre syndrome.
Indeterminate HIV Western blot test.
Prior receipt of the Merck Ad5-based HIV vaccine.
Refusal of any of the individual s intimate contacts to enroll as such on this study.
Primary purpose
Allocation
Interventional model
Masking
300 participants in 4 patient groups
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Central trial contact
Mark Connors, M.D.
Data sourced from clinicaltrials.gov
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