Phase I Study of Vaccination Schedule of Experimental HIV Vaccines
This study will test whether a vaccination schedule of experimental HIV vaccines is safe and whether it causes side effects in healthy adult volunteers. It will also compare the effects of vaccine injected into the muscle (intramuscular), just under the skin (subcutaneous), or into the skin (intradermal) and will monitor the social impact of being in an HIV vaccine study.
Healthy volunteers 18-50 years old may be eligible for this 42-week study. Participants are screened for antibodies to adenovirus, a common virus that causes upper respiratory infections, such as the common cold. Half of the participants selected will be positive and half will be negative for antibodies to the virus.
The vaccines used in this study are known as VRC-HIVDNA016-00-VP (called the "DNA vaccine") and VRC-HIVADV014-00-VP (called the "rAd5 vaccine"). The DNA vaccine codes for four HIV proteins. The rAd5 vaccine is made using an adenovirus that has been modified to contain DNA that codes for three HIV proteins. These vaccines cannot cause HIV or adenoviral infections.
Participants are randomly assigned to one of six possible vaccination schedules that include "prime" and "booster" vaccines. The first vaccinations prime the immune system and the immune response is then boosted later. The groups differ in the type of vaccines given (DNA vaccine prime with rAd5 booster or rAd5 prime with rAd5 booster), in how the vaccine is administered (intramuscularly, subcutaneously or intradermally) and in the schedule of administration. All shots are given in the upper arm. Subjects fill out a diary card at home for 5 days after each vaccination, recording their temperature and any symptoms. The cards are turned in to the clinic at the first visit after all 5 days are completed. Subjects return for clinic visits about 3 days after each prime vaccination and either come in or call the clinic about 7 days after the injection. They call a study nurse 1 or 2 days after the booster vaccination.
Participants have 15-20 clinic visits during the course of the study, depending on their vaccination schedule. At each visit, they are checked for health changes or problems, asked how they are feeling and if they have taken any medications or other treatments, including over-the-counter medicines, herbal supplements, etc. Blood and urine samples are collected at some visits. Subjects are tested for HIV several times and asked questions about their sexual behavior and drug use. Throughout the stu...
|Study Design:||Primary Purpose: Treatment|
|Official Title:||VRC 011: A Phase I Clinical Trial of Intramuscular, Subcutaneous and Intradermal Administration of an HIV-1 Multiclade DNA Vaccine, VRC-HIVDNA016-00-VP, and an HIV-1 Multiclade Adenoviral Vector Vaccine,VRC-HIVADV014-00-VP, in Uninfected Adult Volunteers|
|Study Start Date:||April 2006|
|Study Completion Date:||December 2009|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Drug: VRC-HIVDNA016-00, VRC-HIVADV014-00
The VRC DNA vaccine and VRC recombinant adenoviral vector (rAd5) vaccine have been previously shown to elicit immune responses to HIV-1-specific peptides when administered intramuscularly (IM) alone and in prime-boost schedules. This Phase I, randomized, open-label exploratory study will evaluate the safety and tolerability and the immune responses when IM, subcutaneous (SC) or intradermal (ID) routes of administration are used for the priming vaccinations in a prime-boost schedule. The randomization will ensure that subjects with negative and positive screening adenovirus type 5 antibody (Ad5Ab) titers will be equally represented in each prime-boost schedule evaluated in the study. Group 1 subjects will receive three DNA prime vaccinations followed by a rAd5 boost vaccination and Group 2 subjects will receive one rAd5 prime vaccination followed by a rAd5 boost vaccination. It is also of interest to explore whether vaccination by SC or ID route alters the functional qualities of the immune response. About half of the subjects who screen for HIV vaccine studies at the VRC Clinic have negative Ad5Ab titer and half have positive Ad5Ab titers.
The hypotheses are: 1) IM, SC and ID are all safe routes of administration for both the DNA and rAd5 vaccines; 2) all regimens will elicit immune responses to HIV-1-specific peptides; 3) intradermal administration will allow a lower dosage of the DNA vaccine to be used for eliciting an immune response; and 4) rAd5 booster administered after a rAd5 prime will boost the cellular and humoral immune response. The primary objectives relate to evaluation of the safety and tolerability of the DNA and rAd5 vaccines when administered by IM, SC and ID routes. Secondary objectives are related to evaluation of the immunogenicity of the vaccines when administered by SC and ID routes as compared to the IM route and the social impact of participating in an HIV-1 vaccine trial. Exploratory evaluations of the immunogenicity of the vaccination regimens are also planned.
VRC-HIVDNA016-00-VP (DNA vaccine) is composed of 6 closed, circular DNA plasmids that encode HIV-1 Gag, Pol and Nef (from clade B) and Env glycoprotein from clade A, clade B, and clade C; each plasmid comprises 16.67 percent (by weight) of the vaccine. VRC-HIVADV014-00-VP (rAd5 vaccine) is composed of 4 recombinant non-replicating adenoviral vectors that encode for HIV-1 Gag/Pol polyproteins (from clade B) and Env glycoprotein from clade A, clade B, and clade C, which are combined in a 3:1:1:1 ratio, respectively.
Sixty healthy adult volunteers, 18 to 50 years old, 30 subjects with negative Ad5Ab titers (less than 1:12) and 30 subjects with positive Ad5Ab titers (greater than or equal to 1:12).
Subjects with negative and positive Ad5Ab titers will be equally randomized to the six prime-boost schedules evaluated in the study as shown in the schema below. All injections will be administered by a needle and syringe device appropriate for the route of administration specified.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|