HIV InfectionsPhase 1NCT00270218
Safety of and Immune Response to Two Different HIV Vaccines, Each Followed by a Adenoviral Vaccine Boost, in HIV Uninfected Adults
A Phase 1 study testing VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP and FFB in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial summary
The purpose of this study is to determine the safety of and immune response to an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vector HIV vaccine boost, in HIV uninfected adults. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP and FFB
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 7 sitesUnited States
- Study dates
- Feb 2006to Aug 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- HIV uninfected
- Good general health
- Pre-existing adenovirus 5 (Ad5) neutralizing antibody titers of less than a 1:12 ratio
- Hepatitis B surface antigen negative
- Anti-hepatitis C virus (anti-HCV) antibody negative or negative HCV PCR if anti-HCV antibody is positive
- Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed during the study
Show all 9Show fewer
- Willing to receive HIV test results
- Understand the vaccination procedure
- Willing to use acceptable forms of contraception
Who cannot join
- HIV vaccines or placebos in prior HIV trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
- Immunosuppressive medications within 168 days prior to first study vaccination
- Blood products within 120 days prior to first study vaccination
- Live attenuated vaccines within 30 days prior to first study vaccination
- Investigational research agents within 30 days prior to first study vaccination
- Medically indicated subunit or killed vaccines within 14 days prior to first study vaccination
Show all 25Show fewer
- Current anti-tuberculosis (TB) preventive therapy or treatment
- Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.
- Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol.
- Any job-related responsibility that would interfere with the study
- Serious adverse reactions to vaccines, including hypersensitivity and related symptoms. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
- Autoimmune disease or immunodeficiency
- Active syphilis infection. Participants who have been fully treated for syphilis for more than 6 months prior to study entry are not excluded.
- Moderate to severe asthma. More information on this criterion can be found in the protocol.
- Type 1 or type 2 diabetes mellitus. Participants with histories of isolated gestational diabetes are not excluded.
- Thyroid disease or surgical removal of the thyroid requiring medication during the 12 months prior to study entry
- Accumulation of fluid in the blood vessels (angioedema) within 3 years prior to study entry if episodes are considered serious or have required medication in the 2 years prior to study entry
- Uncontrolled hypertension
- Body mass index (BMI) of 40 or greater OR BMI of 35 or greater if certain other criteria apply. More information about these criteria can be found in the protocol.
- Bleeding disorder
- Cancer. Participants with surgically removed cancer that is unlikely to recur are not excluded.
- Seizure disorder
- Absence of the spleen
- Mental illness that would interfere with the study
- Pregnancy or breastfeeding
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Alabama Vaccine CRS
Birmingham, Alabama, 35294-2041
Vanderbilt Vaccine CRS
Nashville, Tennessee, 37232
NY Blood Ctr./Union Square CRS
New York, New York, 10003
HIV Prevention & Treatment CRS
New York, New York, 10032
Univ. of Rochester HVTN CRS
Rochester, New York, 14642-0001
San Francisco Vaccine and Prevention CRS
San Francisco, California, 94102
FHCRC/UW Vaccine CRS
Seattle, Washington, 98104
About this study
Official title: A Phase I Clinical Trial to Evaluate Immune Response Kinetics and Safety of Two Different Primes, Adenoviral Vector Vaccine (VRC-HIVADV014-00-VP) and DNA Vaccine (VRC-HIVDNA009-00-VP), Each Followed by Adenoviral Vector Boost in Healthy, HIV-1 Uninfected Adults
The purpose of this study is to determine the safety of and immune response to an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vector HIV vaccine boost, in HIV uninfected adults.
Read the detailed description
Evaluating the immunogenicity of HIV vaccines is critical to improving vaccine design and development. The adenoviral vector HIV vaccine VRC-HIVADV014-00-VP has shown immunogenicity in early studies and appeared safe and well tolerated at three different doses in a prior dose-escalation vaccine trial in HIV uninfected adults. The DNA HIV vaccine VRC-HIVDNA009-00-VP has shown immunogenicity in multiple clinical trials; in one trial, the DNA vaccine demonstrated a nearly 100% CD4 T-cell response rate. The DNA plasmids in both vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections. This study will determine the safety and immune response to the administration of an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vaccine boost, in HIV uninfected adults.
This study will last 1 year. Participants will be randomly assigned to one of two groups. Within each group, participants will be randomly assigned to receive either vaccine or control injections. Group 1 participants will receive either placebo or the adenoviral HIV vaccine at study entry and Month 6. Group 2 participants will receive either placebo or the DNA HIV vaccine at study entry and Month 1 and the adenoviral HIV vaccine at Month 6. Participants will be asked to record their temperatures and other side effects in a symptom log on the day of each vaccination and for 3 days thereafter to report any side effects.
Group 1 participants will have 16 study visits, and a physical exam and HIV and pregnancy prevention counseling will occur at each visit. Participants will also be asked about any side effects and medications they are taking. Blood collection will occur at most visits. Urine collection will occur at selected visits. Participants will be asked to complete a social impact assessment at Months 2, 6, and 12 and a testing and belief questionnaire at Months 6 and 12.
- Conditions
- HIV Infections
- Being tested
- VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, FFB, PBS
- Keywords
- HIV Seronegativity, Adenoviral Vector Vaccine, DNA Plasmid Vaccine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VRC-HIVADV014-00-VPBiological
HIV-1 recombinant adenoviral vector vaccine given as a 1 mL intramuscular injection in the deltoid
VRC-HIVDNA009-00-VPBiological
HIV-1 DNA plasmid vaccine given as a 1 mL intramuscular injection in the deltoid
FFBBiological
Adenoviral vector FFB given as a 1 mL intramuscular injection in the deltoid
PBSBiological
phosphate buffered saline
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Arm 1 participants will be given an injection of VRC-HIVADV014-00-VP vaccine on Days 0 and 168. Receives: Biological: VRC-HIVADV014-00-VP |
| 2 | Placebo comparator | Arm 2 participants will be given an injection of final formulation buffer (FFB) on Days 0 and 168. Receives: Biological: FFB |
| 3 | Experimental | Arm 3 participants will be given an injection of VRC-HIVDNA009-00-VP vaccine on Days 0 and 28. Participants will also be given an injection of VRC-HIVADV014-00-VP on Day 168. Receives: Biological: VRC-HIVADV014-00-VP; Biological: VRC-HIVDNA009-00-VP |
| 4 | Placebo comparator | Arm 4 participants will be given an injection of phosphate buffered saline (PBS) on Days 0 and 28 and an injection of FFB on Day 168. Receives: Biological: FFB; Biological: PBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences)
Measured: After each injection and for 6 months after the last injection
Magnitude of HIV-specific CD4+ and CD8+ T-cell responses, defined as percentage of T cells expressing IFN-gamma or IL-2 to vaccine peptide pools
Measured: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Social impact (negative experiences or problems associated with participation in the study and other social, travel, work, school, health care, life insurance, health insurance, housing, military, or other impacts identified by the participant)
Measured: Throughout the study
Secondary outcomes (3)
Expression of HIV-specific T-cell memory differentiation markers and other markers of interest by flow cytometry
Measured: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Titer to HIV-specific binding antibodies assessed by ELISA
Measured: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Titer of HIV-specific neutralization antibodies assessed by neutralizing antibody assay, if indicated
Measured: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2005 (estimated)
- Study startFeb 2006
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stephen De Rosa, MD, Study chair, Fred Hutchinson Cancer Research Center and University of WashingtonSpyros A. Kalams, MD, Study chair, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00270218
- Sponsor's protocol ID
- HVTN 068
- Other IDs
- 10060
- Status last verified
- Oct 2021
- First submitted
- 21 Dec 2005
- Last updated
- 14 Oct 2021
- Results posted
- No
Publications
Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther. 2005 Feb;16(2):149-56. doi: 10.1089/hum.2005.16.149.
PubMed 15761255De Rosa SC, Lu FX, Yu J, Perfetto SP, Falloon J, Moser S, Evans TG, Koup R, Miller CJ, Roederer M. Vaccination in humans generates broad T cell cytokine responses. J Immunol. 2004 Nov 1;173(9):5372-80. doi: 10.4049/jimmunol.173.9.5372.
PubMed 15494483Shiver JW, Emini EA. Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med. 2004;55:355-72. doi: 10.1146/annurev.med.55.091902.104344.
PubMed 14746526Vanniasinkam T, Ertl HC. Adenoviral gene delivery for HIV-1 vaccination. Curr Gene Ther. 2005 Apr;5(2):203-12. doi: 10.2174/1566523053544236.
PubMed 15853728Jin X, Morgan C, Yu X, DeRosa S, Tomaras GD, Montefiori DC, Kublin J, Corey L, Keefer MC; NIAID HIV Vaccine Trials Network. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials. Vaccine. 2015 May 11;33(20):2347-53. doi: 10.1016/j.vaccine.2015.03.036. Epub 2015 Mar 25.
PubMed 25820067
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial to Evaluate Immune Response Kinetics and Safety of Two Different Primes, Adenoviral Vector Vaccine (VRC-HIVADV014-00-VP) and DNA Vaccine (VRC-HIVDNA009-00-VP), Each Followed by Adenoviral Vector Boost in Healthy, HIV-1 Uninfected Adults
- ClinicalTrials.gov ID
- NCT00270218
- Acronym / sponsor ID
- HVTN 068
- Conditions
- HIV Infections
- Keywords
- HIV Seronegativity, Adenoviral Vector Vaccine, DNA Plasmid Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Feb 2006
- Study completion
- Aug 2007 (actual)
- First posted
- 26 Dec 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety of and immune response to an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vector HIV vaccine boost, in HIV uninfected adults.
Detailed description
Evaluating the immunogenicity of HIV vaccines is critical to improving vaccine design and development. The adenoviral vector HIV vaccine VRC-HIVADV014-00-VP has shown immunogenicity in early studies and appeared safe and well tolerated at three different doses in a prior dose-escalation vaccine trial in HIV uninfected adults. The DNA HIV vaccine VRC-HIVDNA009-00-VP has shown immunogenicity in multiple clinical trials; in one trial, the DNA vaccine demonstrated a nearly 100% CD4 T-cell response rate. The DNA plasmids in both vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections. This study will determine the safety and immune response to the administration of an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vaccine boost, in HIV uninfected adults.
This study will last 1 year. Participants will be randomly assigned to one of two groups. Within each group, participants will be randomly assigned to receive either vaccine or control injections. Group 1 participants will receive either placebo or the adenoviral HIV vaccine at study entry and Month 6. Group 2 participants will receive either placebo or the DNA HIV vaccine at study entry and Month 1 and the adenoviral HIV vaccine at Month 6. Participants will be asked to record their temperatures and other side effects in a symptom log on the day of each vaccination and for 3 days thereafter to report any side effects.
Group 1 participants will have 16 study visits, and a physical exam and HIV and pregnancy prevention counseling will occur at each visit. Participants will also be asked about any side effects and medications they are taking. Blood collection will occur at most visits. Urine collection will occur at selected visits. Participants will be asked to complete a social impact assessment at Months 2, 6, and 12 and a testing and belief questionnaire at Months 6 and 12.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: VRC-HIVADV014-00-VPArm 1 participants will be given an injection of VRC-HIVADV014-00-VP vaccine on Days 0 and 168. |
| 2 | Placebo comparator | Biological: FFBArm 2 participants will be given an injection of final formulation buffer (FFB) on Days 0 and 168. |
| 3 | Experimental | Biological: VRC-HIVADV014-00-VP, Biological: VRC-HIVDNA009-00-VPArm 3 participants will be given an injection of VRC-HIVDNA009-00-VP vaccine on Days 0 and 28. Participants will also be given an injection of VRC-HIVADV014-00-VP on Day 168. |
| 4 | Placebo comparator | Biological: FFB, Biological: PBSArm 4 participants will be given an injection of phosphate buffered saline (PBS) on Days 0 and 28 and an injection of FFB on Day 168. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- HIV uninfected
- Good general health
- Pre-existing adenovirus 5 (Ad5) neutralizing antibody titers of less than a 1:12 ratio
- Hepatitis B surface antigen negative
- Anti-hepatitis C virus (anti-HCV) antibody negative or negative HCV PCR if anti-HCV antibody is positive
Key exclusion criteria (25 listed)
- HIV vaccines or placebos in prior HIV trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
- Immunosuppressive medications within 168 days prior to first study vaccination
- Blood products within 120 days prior to first study vaccination
- Live attenuated vaccines within 30 days prior to first study vaccination
- Investigational research agents within 30 days prior to first study vaccination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VRC-HIVADV014-00-VPHIV-1 recombinant adenoviral vector vaccine given as a 1 mL intramuscular injection in the deltoid | Biological | 1, 3 |
| VRC-HIVDNA009-00-VPHIV-1 DNA plasmid vaccine given as a 1 mL intramuscular injection in the deltoid | Biological | 3 |
| FFBAdenoviral vector FFB given as a 1 mL intramuscular injection in the deltoid | Biological | 2, 4 |
| PBSphosphate buffered saline | Biological | 4 |
Primary outcome
Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences)
Time frame: After each injection and for 6 months after the last injection
Magnitude of HIV-specific CD4+ and CD8+ T-cell responses, defined as percentage of T cells expressing IFN-gamma or IL-2 to vaccine peptide pools
Time frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Social impact (negative experiences or problems associated with participation in the study and other social, travel, work, school, health care, life insurance, health insurance, housing, military, or other impacts identified by the participant)
Time frame: Throughout the study
3 secondary outcomes
Expression of HIV-specific T-cell memory differentiation markers and other markers of interest by flow cytometry
Time frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Titer to HIV-specific binding antibodies assessed by ELISA
Time frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Titer of HIV-specific neutralization antibodies assessed by neutralizing antibody assay, if indicated
Time frame: Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2021.
- Background: PubMed 15761255Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther. 2005 Feb;16(2):149-56. doi: 10.1089/hum.2005.16.149.
- Background: PubMed 15494483De Rosa SC, Lu FX, Yu J, Perfetto SP, Falloon J, Moser S, Evans TG, Koup R, Miller CJ, Roederer M. Vaccination in humans generates broad T cell cytokine responses. J Immunol. 2004 Nov 1;173(9):5372-80. doi: 10.4049/jimmunol.173.9.5372.
- Background: PubMed 14746526Shiver JW, Emini EA. Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med. 2004;55:355-72. doi: 10.1146/annurev.med.55.091902.104344.
- Background: PubMed 15853728Vanniasinkam T, Ertl HC. Adenoviral gene delivery for HIV-1 vaccination. Curr Gene Ther. 2005 Apr;5(2):203-12. doi: 10.2174/1566523053544236.
- Derived from this study: PubMed 25820067Jin X, Morgan C, Yu X, DeRosa S, Tomaras GD, Montefiori DC, Kublin J, Corey L, Keefer MC; NIAID HIV Vaccine Trials Network. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials. Vaccine. 2015 May 11;33(20):2347-53. doi: 10.1016/j.vaccine.2015.03.036. Epub 2015 Mar 25.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen De Rosa, MD study chair
Fred Hutchinson Cancer Research Center and University of Washington
Spyros A. Kalams, MD study chair
Vanderbilt University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP and FFB in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences) (time frame: After each injection and for 6 months after the last injection). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00270218, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2021.