"Prime-Boost" Vaccine Schedule for Prevention of HIV Infection
|First Received Date ICMJE||April 29, 2005|
|Last Updated Date||January 23, 2008|
|Start Date ICMJE||April 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00109629 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||"Prime-Boost" Vaccine Schedule for Prevention of HIV Infection|
|Official Title ICMJE||VRC 008: A Phase I Clinical Trial of a Prime-Boost HIV-1 Vaccination Schedule: Multiclade DNA Vaccine, VRC-HIVDNA016-00-VP, Followed by Multiclade Adenoviral Vector Vaccine, VRC-HIVADV014-00-VP, in Uninfected Adult Volunteers|
This study will determine the safety and side effects of two experimental HIV vaccines given in a "prime-boost" schedule. It 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 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 cannot cause HIV or adenoviral infections.
The study will also see if the vaccines cause an immune response; if the injection of the DNA vaccine given using a needle and syringe is similar in safety and immune response to giving them with a needleless injection device called a Biojector 2000; if people who already have antibodies to adenovirus still have an immune response to rAd vaccine; and if there are social harms that result from participating in an HIV vaccine study.
Healthy volunteers between 18 and 50 years of age may be eligible for this 42-week study. Candidates are screened with a medical history, physical examination, blood and urine tests (including pregnancy test for women), and questions regarding sexual behavior and other practices.
Participants receive three injections (shots) of the DNA vaccine and one injection of the rAd vaccine. All injections are given into a muscle in the upper arm (alternating right and left arms with each injection), using a needle and syringe or the needleless Biojector 2000. The first vaccination is given the day of enrollment into the study, and the DNA vaccinations are given about 4 weeks apart from each other, with a minimum of 21 days between injections. The rAd "booster"vaccination is given at Week 24. Participants fill out a diary card at home for 5 days after each vaccination, recording their temperature and any symptoms. They come to the clinic for follow-up 3 days each DNA vaccine injection, and call or return again 7 days after each injection. They call a study nurse 1 or 2 days after the rAd injection.
There are 15 to 18 clinic visits during the course of the study. At each visit, participants are checked for health changes or problems. Blood and urine samples are collected at some visits. Participants are periodically tested for HIV and asked questions about their sexual behavior and drug use and are counseled throughout the study on HIV risk reduction. They are also asked about any social effects they may have experienced as a result of their participation in this study.
Study Design: This is a Phase I randomized study to examine safety and tolerability of, as well as immune response to, a schedule of 3 HIV DNA plasmid vaccinations followed by one HIV adenoviral vector vaccine (rAd) booster. The hypotheses are that: 1) this regimen will be safe for human administration and elicit immune responses to HIV-1; 2) Biojector and Needle/Syringe are both safe to use for IM injection of the DNA vaccine and 3) subjects with both low and high pre-existing adenovirus serotype 5 antibody (Ad5Ab) titer will have a boost in immune response to HIV-1 peptides following the Ad booster vaccination. In this study equal numbers of subjects with high and low Ad5Ab titers will be randomized to receive DNA vaccinations by either needle and syringe (N/S) or by Biojector and then to receive either 1010 PU or 1011 PU rAd booster vaccination in a factorial design. The primary objective is to evaluate the safety and tolerability in humans of the prime-boost vaccination regimen. Secondary objectives are related to evaluation of the immunogenicity of the DNA vaccine when administered by N/S or Biojector, the immunogenicity of the Ad vaccine at two different doses in subjects with high and low pre-enrollment titers of Ad5Ab, the development of adenovirus serotype 5 neutralizing antibody and the social impact of participating in an HIV-1 vaccine trial. Exploratory evaluations of the immunogenicity of the prime-boost regimen are also planned. The preliminary results may serve as the basis for designing studies to provide more definitive answers to questions about method of administration and effect of pre-enrollment Ad5Ab titer on safety of and immune response to the rAd booster vaccination.
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. Vaccine vials will be supplied at 4 mg/mL. DNA vaccinations will be 1 mL of vaccine administered intramuscularly using either N/S or the Biojector 2000 Needle-Free Injection Management System. VRC-HIVADV014-00-VP is a recombinant product composed of four non-replicating adenoviral vectors (in a 3:1:1:1 ratio) that code for HIV-1 Gag/Pol polyproteins from clade B and HIV-1 Env glycoproteins from clades A, B, and C. All rAd injections will be administered by N/S.
Subjects: Forty healthy adult volunteers, 18 to 50 years old; 20 subjects with low Ad5Ab (1:500) and 20 subjects with high Ad5Ab (greater than 1:500).
Study Plan: Forty subjects will be randomized in a 1:1 ratio to receive the same vaccination schedule but by two different methods of intramuscular administration (N/S or Biojector), as shown in the schema. The rAd boost will also be randomized to be either 1010 PU or 1011 PU in 1:1 ratio. The rAd boost dosage will be blinded until 6 weeks of safety and immunogenicity evaluations after the rAd boost are completed for all subjects.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Primary Purpose: Treatment|
|Condition ICMJE||HIV Infections|
|Study Arm (s)||Not Provided|
|Publications *||Graham BS, Enama ME, Nason MC, Gordon IJ, Peel SA, Ledgerwood JE, Plummer SA, Mascola JR, Bailer RT, Roederer M, Koup RA, Nabel GJ; VRC 008 Study Team. DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial. PLoS One. 2013;8(4):e59340. doi: 10.1371/journal.pone.0059340. Epub 2013 Apr 8.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Completion Date||January 2008|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
A participant must meet all of the following criteria:
No reproductive potential because of menopause [one year without menses] or because of a hysterectomy, bilateral oophorectomy, or tubal ligation,
Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 42 of the study,
Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 42 of the study by one of the following methods:
A volunteer will be excluded if one or more of the following conditions apply:
Fasting blood glucose greater than 125 mg/dL
Note: The fasting blood tests require 8 hours fast prior to the blood draw. The results used for eligibility screening must be from tests completed no more than 12 weeks (84 days) prior to day of enrollment. The individual criteria for BMI (inclusion item 10) and blood pressure (exclusion item 16) must also be met.
|Ages||18 Years to 50 Years (Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00109629|
|Other Study ID Numbers ICMJE||050148, 05-I-0148|
|Has Data Monitoring Committee||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||January 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP