Vaccine Treatment for HIV-Infection
This study will determine the safety and side effects of an experimental adenoviral vector vaccine given to patients who previously received a different HIV vaccine (VRC-HIVDNA016-00-VP) in a prior NIAID study. The study will also monitor participants for the social impact of being in an HIV vaccine study (e.g., problems with insurance, health care, friends, family, employment, housing, and so forth). The study vaccine is made using an adenovirus (a common virus that causes upper respiratory infections, such as the common cold, eye infection, urine infection or diarrhea) that has been modified to contain DNA that codes for three HIV proteins. The modified virus cannot reproduce in the body and cannot cause HIV disease or adenoviral infections.
Healthy volunteers who previously received three injections of the VRC-HIVDNA016-00-VP under the NIAID study VRC 007 (protocol 04-I-0254) may be eligible for this study.
Participants receive one injection of the adenoviral vector vaccine. It is given the day they enroll in the study, as a single injection in an upper arm muscle. Also on that day they have a brief physical examination, medical history, blood and urine tests, pregnancy test for women, and counseling, as needed, about HIV and pregnancy avoidance. Subjects are observed for side effects for at least 30 minutes after the vaccination and are required to telephone the clinic staff 1 to 2 days after the injection for follow-up. In addition, they are given a diary card to take home, on which they record their temperature and any symptoms daily for 5 days.
Subjects return to the clinic for 5 follow-up visits at weeks 2, 4, 6, 12 and 24 after the injection. At each visit they are checked for health changes or problems since the last visit, asked how they are feeling and what medications they are taking. They have blood drawn at every visit and urine samples collected at most visits. They are tested for HIV three or more times and are questioned about their sexual behavior and drug use. They also complete a "social impact" questionnaire at the last visit.
Subjects are asked to undergo apheresis at the week 4 visit. This procedure allows collection of a larger number of white blood cells than can be obtained by a simple blood draw. The white cells are studied to see how the immune system responds to the study vaccine. For apheresis, blood is collected through a needle in an arm vein and spun in a machine that separates the components. The white blood cells are extracted and the rest of the blood is returned to the body through the same needle. Subjects who do not undergo apheresis have about 1/3 cup of blood sample drawn using a needle.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Booster Dose of a Recombinant Multiclade HIV-1 Adenoviral Vector Vaccine, VRC-HIVADV014-00-VP, in Uninfected Subjects Who Where Previously Immunized With VRC-HIVDNA016-00-VP in VRC 00|
|Study Start Date:||April 2005|
|Estimated Study Completion Date:||January 2008|
Study Design: This is a Phase I open-label study to examine safety, tolerability and immune response of a multiclade HIV adenoviral vector vaccine as a booster vaccination in uninfected adults. The hypothesis is that this vaccine will be safe as a booster vaccine and elicit immune responses to HIV. The primary objective is to evaluate the safety and tolerability of a VRC-HIVADV014-00-VP booster vaccination in uninfected subjects who previously received 3 injections of VRC-HIVDNA016-00-VP. The secondary objectives include immunogenicity evaluations, adenovirus serotype 5 (Ad5) antibody titers, and social impacts. Exploratory evaluations include epitope mapping and other immunogenicity evaluations.
Product Description: VRC-HIVADV014-00-VP (rAd) is a recombinant product composed of 4 adenoviral vectors (in a 3:1:1:1 ratio) that encode the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env glycoproteins from clades A, B, and C, respectively.
Subjects: Healthy adult volunteers who previously received three injections of VRC-HIVDNA016-00-VP at a dosage of 4 mg in the VRC 007 study (04-I-0254). The subjects in these groups were between 20 and 36 years old at time of enrollment in VRC 007; those who participate in VRC 010 will be no more than 36 weeks older at the time of enrollment into VRC 010.
Study Plan: Up to fourteen volunteers will receive one 1 mL injection of the study agent at a dosage of 1010 particle units (PU) intramuscularly (IM) in a deltoid muscle. Safety and immunogenicity will be evaluated by follow-up visits over the subsequent 24 weeks. The peripheral blood mononuclear cell (PBMC) sample for immunogenicity studies collected at Week 4 after vaccination will be obtained by apheresis if the subject is willing and eligible for apheresis and an apheresis appointment can be conveniently scheduled in the interval specified; otherwise PBMCs will be obtained from 80 mL blood collected by phlebotomy.
Study Duration: Subjects will be evaluated at 6 or more clinical visits for 24 weeks after the study injection.
Study Endpoints: The primary endpoint is safety of the vaccine administered at a dose of 10(10) PU by IM injection. Secondary endpoints are immunogenicity as indicated by HIV-specific antibody through Week 4, cellular immune responses through Week 6, Ad5 antibody titer at Week 0 and Week 4 and social impact at Week 24. Exploratory analyses include immunogenicity at Weeks 12 and 24, Ad5 antibody titer at Week 24 and epitope mapping of the CD8+ and CD4+ T cell responses at Week 4.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|