Immune Responses to Two Experimental HIV Vaccines in Healthy Adults
|First Received Date ICMJE||June 30, 2011|
|Last Updated Date||March 26, 2014|
|Start Date ICMJE||June 2011|
|Primary Completion Date||March 2014 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||To describe the kinetics and patterns over the time of innate and adaptive immunologic responses in peripheral blood as well as the pattern of adaptive immune responses at a single timepoint in mucosal samples following vaccination with the rAd5...|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01386489 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||To assess the safety and tolerability of the investigational vaccines.|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Immune Responses to Two Experimental HIV Vaccines in Healthy Adults|
|Official Title ICMJE||VRC 016: A Phase 1b Open-Label, Randomized Clinical Trial to Evaluate Early Innate and Adaptive Immune Responses to the Investigational HIV-1 Vaccines: VRC-HIVADV014-00-VP and VRC-HIVDNA016-00-VP in Ad5 Seronegative Healthy Adults|
The primary focus of the Vaccine Research Center (VRC) at the NIH is to develop vaccines for HIV/AIDS. The main purpose of this study is to look in detail at the body s immune response to two experimental HIV vaccines currently in development at the VRC. One is known as the rAd5 vaccine and the other is known as the DNA vaccine. These vaccines are made with pieces of manufactured DNA. They do not contain live or killed HIV. It is impossible for study vaccines to give you HIV and they cannot cause you to give HIV to someone else. Both of these experimental vaccines have been given to people before in other research studies. They have not been approved for treating or preventing HIV infection.
The main purpose of this study is to look in detail at the body s immune responses after the experimental HIV vaccines are given and to assess safety of the study vaccines.
Healthy volunteers between the ages of 18 and 50 who are not infected with HIV and who meet the eligibility requirements.
Participants will be screened with a medical history (including questions about sexual history and drug use), physical exam, and blood tests.
The study will have two groups:
< TAB> One group will receive one injection of the rAd5 vaccine, and have 8 clinic visits over 3 months.
< TAB> The second group will have three injections of the DNA vaccine, one injection of the rAd5 vaccine, and have 12 clinic visits over 6 months.
All participants will be asked to provide blood and body fluid samples for testing during the study.
Payment for participation will be provided.
This is a hypothesis-generating descriptive study to evaluate the kinetics and pattern of early innate and adaptive immune responses to the VRC recombinant adenoviral vector serotype 5 vaccine, VRC-HIVADV014-00-VP (rAd5). The rAd5 vaccine has been previously administered to more than 1000 study subjects and characterized as safe and immunogenic. A difference in the pattern of vaccine antigen-specific immune responses observed when rAd5 is given as a single agent compared to after priming by a 6-plasmid DNA vaccine, VRCHIVDNA016-00-VP, has previously been reported. This study will randomize vaccine-naive subjects to receive a single injection of rAd5 or to the DNA primerAd5 boost regimen that is now in a large Phase II study. Collection of blood, rectal, oral and genital specimens for characterization of early innate and adaptive immune responses will follow receipt of rAd5. The hypothesis is that the pattern of early innate and adaptive immune responses elicited by the rAd5 vaccine administered after priming with DNA vaccine will be distinctly different from the pattern elicited when rAd5 is administered as a single agent. The primary objectives are to describe the kinetics and pattern of early innate and adaptive immune responses that occur in blood samples early after administration of rAd5 vaccine alone and after administration following 3 DNA prime injections. Secondary and exploratory objectives are related safety, as well as the pattern of immune responses in mucosal samples and in blood samples.
VRC-HIVDNA016-00-VP [6-plasmid DNA vaccine] is composed of 6 closed, circular DNA plasmids that encode for HIV-1 Gag, Pol and Nef proteins (from clade B) and Env glycoproteins from clade A, clade B, and clade C, which are combined in equal proportions. All injections will be at 4 mg dose in a 1 mL volume administered intramuscularly (IM) by Biojector (registered trademark) into deltoid muscle.
VRC-HIVADV014-00-VP (rAd5 vaccine) is composed of 4 recombinant nonreplicating adenoviral vectors that encode for HIV-1 Gag/Pol polyproteins (from clade B) and Env glycoproteins from clade A, clade B, and clade C, which are combined in a 3:1:1:1 ratio, respectively, in a final formulation buffer (FFB). All injections will be at 10(10) PU dose in a 1 mL volume administered IM by needle and syringe into deltoid muscle.
The study target accrual is at least 20 subjects who complete collection of blood, oral, rectal and genital specimens through 2 weeks after the rAd5 vaccination. To account for potential discontinuations from the study, enrollment may include up to 36 HIV-uninfected adults, ages 18-50 years old that are HIV vaccine-naive and adenovirus serotype 5 (Ad5) antibody negative at screening; males must be fully circumcised.
Subjects will be randomized at a 1:1 ratio to receive a single injection of rAd5 or the DNA prime-rAd5 boost schedule and will be stratified by gender to achieve approximately equal distribution of each gender into the two vaccination schedules. Subjects randomized to Group 1 may receive the vaccination on enrollment day or schedule the day of vaccination to occur within 6 weeks followed by the expected 24 hours in the inpatient unit and day 3 post-vaccination sample collections for the frequent sampling that will immediately ensue according to the sample collection schedule. Subjects randomized to Group 2 will receive the first of three DNA vaccinations and schedule projected dates for the subsequent injections and timepoints with intensive sample collection schedules. Due to the need to commit to about 3 days of disruption in normal daily activities, starting with the day of rAd5 vaccination on either schedule, flexibility in scheduling of the rAd5 vaccination is included in the protocol plan.
Subjects from both groups will be admitted to the NIH Clinical Center overnight for the first 24 hours following vaccination with rAd5. On the rAd5 vaccination day, peripheral blood samples will be collected for serum, plasma and peripheral blood mononuclear cells at seven target time points in the first 24 hours as follows: pre-injection and post-injection hours 1, 3, 6, 12, 18 and 24; then days 3, 5, 7, 14 and 28 post-rAd5 vaccine. Mucosal sampling will occur on day 14 after rAd5 vaccine. This will include buccal mucosa, rectal secretions, cervical secretions (from women) and semen samples (from men). There will be a blood collection to assess innate immunity following the 3rd DNA vaccination in Group 2 with blood draws at pre-injection and at post-injection hours 1, 3, 6 and 18.
The safety of vaccinations and the research plan will be monitored by a protocol safety review team.
Subjects will be followed in the clinic through 12 weeks after last study injection and contacted for long term follow-up 12 weeks later and then every 48 weeks through Study Week 144.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||March 2014|
|Primary Completion Date||March 2014 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
A volunteer must meet all of the following criteria:
No reproductive potential because of menopause [one year without menses] or because of tubal ligation,
Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through 12 weeks after the last vaccination on the study schedule,
Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through 12 weeks after the last vaccination on the study schedule by one of the following methods:
A volunteer will be excluded if one or more of the following conditions apply:
|Ages||18 Years to 50 Years|
|Accepts Healthy Volunteers||No|
|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||NCT01386489|
|Other Study ID Numbers ICMJE||110197, 11-I-0197|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||March 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP