Safety and Immune Response to a Prime-Boost Vaccination Schedule in HIV-infected Patients
Study Design: This is a Phase I, randomized, placebo-controlled, double-blinded study to examine safety, tolerability and immune response of a prime-boost vaccination regimen for treatment of HIV infection. The vaccination schedule consists of three injections of a multiclade HIV plasmid DNA vaccine followed by one injection of a multiclade recombinant adenoviral vector vaccine (rAd), in HIV-infected adults. The hypothesis is that this vaccination regimen will be safe and elicit an immune response in HIV-infected subjects. The primary objectives are related to evaluating the safety and tolerability of the vaccination regimen and assessing the effect of vaccination on humoral and cellular immune responses to vaccine-specific HIV antigens.
Product Description: VRC-HIVDNA016-00-VP is composed of 6 closed, circular DNA plasmids that are each 16.67% (by weight) of the vaccine. Each of the 6 plasmids in this vaccine expresses a single gene product. Plasmids VRC 4401, VRC 4409 and VRC 4404 are designed to express clade B HIV-1 Gag, Pol and Nef, respectively. VRC 5736, VRC 5737, and VRC 5738 are designed to express HIV-1 Env glycoprotein from clade A, clade B, and clade C, respectively. Each DNA vaccination will be 1 mL of vaccine administered intramuscularly (IM) using the Biojector 2000 Needle-Free Injection Management System. Phosphate buffered saline (PBS) will be used as the placebo for the DNA vaccine.
VRC-HIVADV014-00-VP (rAd) 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. Injections of 10(10) PU will be administered IM by needle and syringe. The final formulation buffer (FFB) will be used as the placebo for the rAd vaccine.
Subjects: HIV-infected adult volunteers (18-50 years old) on stable highly active antiretroviral therapy (HAART) therapy who have a CD4+ cell count greater than 350 cells/mm3 and have had a viral load (VL) less than 400 copies/mL for at least six months and a viral load of less than 50 copies/mL within 4 weeks prior to enrollment.
Study Plan: Fifteen volunteers will be enrolled and randomized in a 2:1 ratio to vaccine:control (10 DNA prime with rAd boost:5 PBS with FFB placebo). A Data and Safety Monitoring Board (DSMB) will review the study every 6 months. Subjects will be evaluated for safety and immunogenicity for 48 weeks, which is 24 weeks after the target date for the booster vaccination.
Study Duration: Subjects will be followed for 48 weeks after enrollment into the study.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||VRC101: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Prime-Boost HIV-1 Vaccination Schedule of a 6-Plasmid Multiclade HIV-1 DNA Vaccine, VRC-HIVDNA016-00-VP, Followed by a Recombinant Multiclade Adenoviral Vector HIV Vaccine|
|Study Start Date:||December 2005|
|Study Completion Date:||June 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
This study will determine the safety and side effects of two experimental HIV vaccines and see if vaccination can enhance the pre-existing HIV-specific immune response in HIV-infected individuals on anti-retroviral therapy . The vaccines are VRC-HIVDNA016-00-VP (called the "DNA vaccine") and VRC-HIVADV014-00-VP (called the "rAd vaccine"). The DNA vaccine codes for four HIV proteins. The rAd vaccine is made using an adenovirus (a common virus that causes upper respiratory infections, such as the common cold) that has been modified to contain DNA that codes for three HIV proteins. These vaccines will be given in a "prime-boost" schedule and cannot cause HIV or adenoviral infections.
HIV-infected people between 18 and 50 years old who are on a stable treatment plan for HIV with highly active antiretroviral (ARV) drugs, have a CD4+ T cell count greater than 350, and have a low viral load may be eligible for this 48-week study.
Participants receive an injection (shot) of the DNA vaccine or a placebo (solution that does not contain any vaccine, medicine, or drugs) the day they enter the study and again at study weeks 4 and 8. They receive a booster injection of the rAd vaccine or placebo at week 24. The DNA vaccines are given with a needle-less injection device called the "Biojector 2000(Registered Trademark)" and the rAd vaccine is given using a needle and syringe. All shots are given in the upper arm muscle, alternating right and left arms with each injection. Patients 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. Patients must call a study nurse 1 or 2 days after each of the four injections and again 7 or 8 days after each of the first three injections.
Patients have 12 clinic visits during the course of the study. 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 samples are drawn at every visit and urine samples are collected at some visits.
At week 28 (4 weeks after the fourth injection), patients undergo apheresis, a procedure for collecting large numbers of white blood cells. The cells are tested in the laboratory to see how the immune system responds to the study vaccine. For the procedures, blood is collected through a needle in an arm vein and spun in a machine that separates the white blood cells from the rest of the blood (red cells, plasma and platelets). The white cells are removed and the rest of the blood is returned to the patient's body through the same needle. Patients who cannot or do not want to undergo apheresis have 80 mL (about 1/3 cup) of blood drawn through a needle and collected in blood collection tubes.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|