Safety and Immunogenicity of an HIV Vaccine in Normal Adult Volunteers
This study will test the safety of an experimental vaccine against HIV infection and see if it causes an immune response to HIV. The vaccine is given by injection (shot) in the upper arm. It is made from DNA that codes for three HIV proteins. The DNA is inserted into an adenovirus that carries it into the muscle cells. The adenovirus normally can cause eye or upper respiratory infections, such as a cold; however, for the vaccine, it has been modified so that it cannot cause illness. Nor can the vaccine cause HIV infection, because it codes for only three of the nine HIV proteins.
Healthy, normal volunteers between 18 and 44 years of age who are not HIV-infected may be eligible for this study. Candidates are screened with a medical history and physical examination and blood and urine tests.
Participants are randomly assigned to receive either the experimental vaccine or a placebo (an inactive substance that looks like the vaccine). The vaccine or placebo is administered to participants in groups, according to their entry into the study. The first group receives the lowest study dose of vaccine. If this dose is safe, then the second group receives a higher dose. If this dose is also safe, then the third and final group receives the highest study dose. Clinic staff observe the subjects for side effects for 30 minutes after the injection, and subjects keep a diary card for the next 5 days, recording their temperature and any symptoms that may appear. Subjects are contacted by a nurse 2 days after the injection for follow-up.
Participants are seen at the clinic for follow-up visits 1, 2, 4, 12, and 24 weeks after the injection, and then are contacted by telephone for follow-up once a year until 5 years after the injection. The clinic visits include a physical examination, medical history, blood and urine tests, and HIV counseling, as needed. Women have pregnancy tests at the screening evaluation and again at study week 24. All subjects are tested for HIV at screening and at study weeks 12 and 24, and all subjects complete a "social impact questionnaire" at week 24. All subjects are asked questions about their sexual behavior and drug use.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Recombinant Multiclade HIV-1 Adenoviral Vector Vaccine, VRC-HIVADV014-00-VP, in Uninfected Adult Volunteers|
|Study Start Date:||May 2004|
|Study Completion Date:||October 2009|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
This is a Phase I, randomized, placebo-controlled, double-blinded study to examine safety, tolerability and immune response of a multiclade HIV adenoviral vector vaccine in uninfected adults. The hypothesis is that this vaccine will be safe and elicit immune responses to HIV. The primary objective is to evaluate the safety and tolerability of VRC-HIVADV014-00-VP in uninfected subjects and the secondary objectives include immunogenicity evaluations and adenovirus serotype 5 (Ad5) antibody titers through Week 4 and social impacts at Week 24. Exploratory evaluations include immunogenicity evaluations at Weeks 12 and 24 and Ad5 antibody titers at Week 24.
VRC-HIVADV014-00-VP is a recombinant product composed of 4 adenoviral vectors (Ad) (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. The final formulation buffer, VRC-DILUENT013-DIL-VP will be used as the diluent and as the placebo control. Injections will be administered intramuscularly (IM).
Healthy adult volunteers (18 to 44 years old).
Thirty-six volunteers will receive one 1.0 mL injection of the study agent or placebo in a deltoid muscle as shown in the schema. Dose escalation will occur about three weeks after the last injection in a dose group following an interim safety data review by a DSMB, provided that there are no significant toxicities.
Subjects will be evaluated at 5 or more clinical visits for 24 weeks after the study injection, followed by annual telephone or mail contact for the subsequent 4 years.
The primary endpoint is safety of the vaccine administered at doses of 1 x 10(9), 1 x 10(10) and 1 x 10(11) particle units (PU) by intramuscular injection. Secondary endpoints are immunogenicity as indicated by HIV-specific antibody and cellular immune responses through Week 4, Ad5 antibody titer at Week 0 and Week 4 and social impact at Week 24. Exploratory analyses of immunogenicity at Weeks 12 and 24 and Ad5 antibody titer at Week 24 will also be performed.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|