HIV InfectionsPhase 1NCT00955006
Immune Response to an HIV DNA Plasmid Vaccine Prime Followed by Adenovirus Boost in HIV-uninfected Individuals
A Phase 1 study testing VRC-HIVDNA-016-00-VP and VRCHIVADV014-00-VP in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of the study is to determine the safety of mucosal immune responses to a DNA HIV vaccine followed by an adenoviral vector HIV vaccine 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-HIVDNA-016-00-VP and VRCHIVADV014-00-VP
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to 22 Nov 2017
- 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
- Access to participating HVTN CRS and willingness to be followed for the planned duration of the study
- Ability and willingness to provide informed consent
- Assessment of understanding: participant demonstrates understanding of this study and the Step Study results; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- Willingness to receive HIV test results
- Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required clinic visit, and willing to continue annual follow-up contact after the last required clinic visit, for a total of 5 years following enrollment
- Agrees not to enroll in another study of an investigational research agent prior to completion of last required protocol clinic visit (excludes annual follow-up contact for safety surveillance)
Show all 22Show fewer
- Assessed by clinic staff as being at "low risk" for HIV infection. More information on this criterion can be found in the protocol.
- Good general health as shown by medical history, physical exam, and screening laboratory tests. More information on this criterion can be found in the protocol.
- Neutralizing antibody titers of Ad5 less than 1:18
- Hemoglobin equal to or greater than 11.0 g/dL for participants who were born female, 12.5 g/dL for participants who were born male
- White blood cell (WBC) count = 3,300 to 12,000 cells/mm^3
- Total lymphocyte count equal to or greater than 800 cells/mm^3
- Remaining differential either within institutional normal range or accompanied by site physician approval
- Platelets = 125,000 to 550,000/mm^3
- Prothrombin time (PT) less than 1.5 and partial thromboplastin time (PTT) less than 1.25 greater than upper limits of normal
- Alanine transaminase (ALT) is less than 2.5 times the institutional upper limit of normal
- Negative HIV-1 and 2 blood test: participants must have a negative FDA-approved enzyme immunoassay (EIA)
- For participants born female, normal Pap smear or ASCUS with no evidence of high risk HPV within 3 years prior to enrollment
- Participants who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed on the day of initial vaccination prior to vaccination
- Participants who were born female must agree to consistently use effective contraception from at least 21 days prior to enrollment through the last required clinic visit for sexual activity that could lead to pregnancy; or not be of reproductive potential; or be sexually abstinent. More information on this criterion can be found in the protocol.
- Participants who were born female must also agree not to seek pregnancy through alternative methods such as artificial insemination or in vitro fertilization until after the last required clinic visit
- If born male, must be fully circumcised (as documented at a screening examination)
Who cannot join
- Excessive daily alcohol use or frequent binge drinking or chronic marijuana abuse or any other use of illicit drugs within the past 12 months
- A history of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), Chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B in the past 12 months
- HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, the HVTN 076 PSRT will determine eligibility on a case-by-case basis.
- Experimental vaccine(s) received within the last 5 years in a prior vaccine trial. More information on this criterion can be found in the protocol.
- Immunosuppressive medications received within 168 days before first vaccination (eg, oral/parenteral corticosteroids, and/or cytotoxic medications). People taking corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
- Abnormality of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of hemorrhoids)
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- Blood products received within 120 days before first vaccination
- Immunoglobulin received within 60 days before first vaccination
- Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after vaccination (e.g., measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)
- Influenza vaccine or any vaccines that are not live attenuated vaccines received within 14 days prior to first vaccination or scheduled within 14 days after vaccination (e.g., influenza, tetanus, pneumococcal, hepatitis A or B)
- Investigational research agents received within 30 days before first vaccination
- Intent to participate in another study of an investigational research agent during the planned duration of the study
- Allergy treatment with antigen injections within 30 days before first vaccination or scheduled within 14 days after injection
- Current anti-tuberculosis (TB) prophylaxis or therapy
- Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. More information on this criterion can be found in the protocol.
- Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent
- Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. Participants who had a nonanaphylactic adverse reaction to pertussis vaccine as a child are not excluded.
- Autoimmune disease
- Immunodeficiency
- Active syphilis infection. (Not excluded: syphilis fully treated over 6 months prior to enrollment)
- Reports one or more perianal HSV outbreaks within 30 days prior to enrollment
- Positive gonorrhea or Chlamydia urine nucleic acid amplification test (NAAT)
- Participants reporting receptive anal intercourse in the last 12 months: positive rectal gonorrhea or Chlamydia test by NAAT or culture
- Asthma other than mild, well-controlled asthma. More information on this criterion can be found in the protocol.
- History of partial or complete hysterectomy
- History of valvular heart disease
- Diabetes mellitus type 1 or type 2, including cases controlled with diet alone
- Thyroidectomy, or thyroid disease requiring medication during the last 12 months
- Angioedema within the last 3 years if episodes are considered serious or have required medication within the last 2 years
- Hypertension. More information on this criterion can be found in the protocol.
- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
- Malignancy. (Not excluded: a participant with a surgical excision and subsequent observation period that in the investigator's estimation has a reasonable assurance of sustained cure or is unlikely to recur during the period of the study.)
- Seizure disorder. (Not excluded: a participant with a history of seizures who has not required medications or had a seizure for 3 years.)
- Asplenia: any condition resulting in the absence of a functional spleen
- Psychiatric condition that precludes compliance with the protocol
- Pregnant or breastfeeding
- If born male, has been circumcised within 90 days prior to first vaccination or displays evidence that surgical site is not fully healed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Seattle Vaccine and Prevention CRS
Seattle, Washington, 98109-1024
About this study
Official title: A Phase 1b Clinical Trial to Evaluate Mucosal Immune Responses to a DNA Plasmid Vaccine Prime Followed by an HIV-1 Adenoviral Vector Boost in Healthy Adenovirus Type 5 Seronegative HIV-1-uninfected Adults
The purpose of the study is to determine the safety of mucosal immune responses to a DNA HIV vaccine followed by an adenoviral vector HIV vaccine in HIV uninfected adults.
Read the detailed description
The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. This study will evaluate the safety and immunogenicity of an experimental multiclade HIV vaccine, VRC-HIVDNA016-00-VP, followed by a similarly structured adenovirus-vectored vaccine boost, VRC-HIVADV014-00-VP, in HIV uninfected adults. The DNA plasmids in both the vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. The study's primary objective is to investigate the ability of a 6-plasmid DNA prime followed by a rAd5 boost to elicit HIV-specific cellular immune responses at mucosal surfaces.
This study will last 12 months and participants will visit the clinic 15 times. Participants will receive three injections of the VRC-HIVDNA016-00-VP vaccine at Months 0, 1, and 2 followed by an injection of VRC-HIVADV014-00-VP at Month 6. All injections will be given in the upper arm. At study visits participants will have a physical, medical history taken, blood collection, and risk reduction counseling. At some visits, rectal biopsies (via anoscopy or, optionally, by flexible sigmoidoscopy), saliva, semen, cervical and/or vaginal fluid samples will also be collected. Pregnancy testing for women will be done prior to each vaccination and study procedure.
Participants will be contacted by study staff once a year for 5 years after the initial study visit for follow-up health and safety monitoring.
- Conditions
- HIV Infections
- Being tested
- VRC-HIVDNA-016-00-VP, VRCHIVADV014-00-VP
- Keywords
- HIV Seronegativity, HIV Preventive 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-HIVDNA-016-00-VPBiological
Composed of six DNA plasmids in equal concentrations that encode Gag, Pol, and Nef from clade B (strains HXB2, NL4-3, NY5/BRU) and the HIV-1 Env glycoproteins from clade A (strain 92rw020), clade B (strains HXB2/BaL), and clade C (strain 97ZA012). Vaccine will be administered intramuscularly (IM) in the deltoid via needle-free Biojector.
VRCHIVADV014-00-VPBiological
A mixture of 4 recombinant serotype 5 adenoviral replication deficient vectors, each expressing HIV-1 proteins (clade B Gag-Pol fusion, clade A Env, clade B Env, clade C Env). Administered IM via needle and syringe.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Participants will receive three injections of VRC-HIVDNA-016-00-VP at Months, 0, 1, and 2 and one injection of VRCHIVADV014-00-VP at Month 6. Receives: Biological: VRC-HIVDNA-016-00-VP; Biological: VRCHIVADV014-00-VP |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIV-specific T-cell response rates detected in specimens collected from the rectum, semen, or cervix as assessed by IFN-γ ELISpot assay and/or flow cytometry
Measured: Throughout study
Secondary outcomes (6)
Local and systemic reactogenicity signs and symptoms, adverse events and severe adverse events.
Measured: Throughout study
Induction of mucosal homing markers on HIV-specific T-cells as assessed by flow cytometric assays of peripheral blood samples
Measured: Throughout study
Multiparameter flow cytometric analyses of dendritic and NK cells in PBMCs, analysis of cytokines and chemokines using a multiplex assay of serum, plasma, semen, cervical secretions and dried blood spots, and gene expression analysis of RNA from PBMCs.
Measured: Throughout study
Flow cytometric analysis of T-cell activation and subsets detected in specimens collected from the rectum, semen, or cervix
Measured: Throughout study
Adenovirus-specific T-cell response rates detected in specimens collected from the rectum, semen, or cervix as assessed by IFN-γ ELISpot assay and/or flow cytometry
Measured: Throughout study
HIV-specific IgA and IgG responses in saliva, cervical secretions, semen, which may include neutralizing activity
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2009 (estimated)
- Study startMay 2011
- Primary completionSep 2013
- Study completion22 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Janine Maenza, Study chair, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00955006
- Sponsor's protocol ID
- HVTN 076
- Other IDs
- 10625
- Status last verified
- Oct 2021
- First submitted
- 5 Aug 2009
- Last updated
- 14 Oct 2021
- Results posted
- No
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 1b Clinical Trial to Evaluate Mucosal Immune Responses to a DNA Plasmid Vaccine Prime Followed by an HIV-1 Adenoviral Vector Boost in Healthy Adenovirus Type 5 Seronegative HIV-1-uninfected Adults
- ClinicalTrials.gov ID
- NCT00955006
- Acronym / sponsor ID
- HVTN 076
- Conditions
- HIV Infections
- Keywords
- HIV Seronegativity, HIV Preventive Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- May 2011
- Primary completion
- Sep 2013 (actual)
- Study completion
- 22 Nov 2017 (actual)
- First posted
- 7 Aug 2009 (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 the study is to determine the safety of mucosal immune responses to a DNA HIV vaccine followed by an adenoviral vector HIV vaccine in HIV uninfected adults.
Detailed description
The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. This study will evaluate the safety and immunogenicity of an experimental multiclade HIV vaccine, VRC-HIVDNA016-00-VP, followed by a similarly structured adenovirus-vectored vaccine boost, VRC-HIVADV014-00-VP, in HIV uninfected adults. The DNA plasmids in both the vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. The study's primary objective is to investigate the ability of a 6-plasmid DNA prime followed by a rAd5 boost to elicit HIV-specific cellular immune responses at mucosal surfaces.
This study will last 12 months and participants will visit the clinic 15 times. Participants will receive three injections of the VRC-HIVDNA016-00-VP vaccine at Months 0, 1, and 2 followed by an injection of VRC-HIVADV014-00-VP at Month 6. All injections will be given in the upper arm. At study visits participants will have a physical, medical history taken, blood collection, and risk reduction counseling. At some visits, rectal biopsies (via anoscopy or, optionally, by flexible sigmoidoscopy), saliva, semen, cervical and/or vaginal fluid samples will also be collected. Pregnancy testing for women will be done prior to each vaccination and study procedure.
Participants will be contacted by study staff once a year for 5 years after the initial study visit for follow-up health and safety monitoring.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: VRC-HIVDNA-016-00-VP, Biological: VRCHIVADV014-00-VPParticipants will receive three injections of VRC-HIVDNA-016-00-VP at Months, 0, 1, and 2 and one injection of VRCHIVADV014-00-VP at Month 6. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- Access to participating HVTN CRS and willingness to be followed for the planned duration of the study
- Ability and willingness to provide informed consent
- Assessment of understanding: participant demonstrates understanding of this study and the Step Study results; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- Willingness to receive HIV test results
- Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required clinic visit, and willing to continue annual follow-up contact after the last required clinic visit, for a total of 5 years following enrollment
Key exclusion criteria (37 listed)
- Excessive daily alcohol use or frequent binge drinking or chronic marijuana abuse or any other use of illicit drugs within the past 12 months
- A history of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), Chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B in the past 12 months
- HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, the HVTN 076 PSRT will determine eligibility on a case-by-case basis.
- Experimental vaccine(s) received within the last 5 years in a prior vaccine trial. More information on this criterion can be found in the protocol.
- Immunosuppressive medications received within 168 days before first vaccination (eg, oral/parenteral corticosteroids, and/or cytotoxic medications). People taking corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
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-HIVDNA-016-00-VPComposed of six DNA plasmids in equal concentrations that encode Gag, Pol, and Nef from clade B (strains HXB2, NL4-3, NY5/BRU) and the HIV-1 Env glycoproteins from clade A (strain 92rw020), clade B (strains HXB2/BaL), and clade C (strain 97ZA012). Vaccine will be administered intramuscularly (IM) in the deltoid via needle-free Biojector. | Biological | Group 1 |
| VRCHIVADV014-00-VPA mixture of 4 recombinant serotype 5 adenoviral replication deficient vectors, each expressing HIV-1 proteins (clade B Gag-Pol fusion, clade A Env, clade B Env, clade C Env). Administered IM via needle and syringe. | Biological | Group 1 |
Primary outcome
HIV-specific T-cell response rates detected in specimens collected from the rectum, semen, or cervix as assessed by IFN-γ ELISpot assay and/or flow cytometry
Time frame: Throughout study
6 secondary outcomes
Local and systemic reactogenicity signs and symptoms, adverse events and severe adverse events.
Time frame: Throughout study
Induction of mucosal homing markers on HIV-specific T-cells as assessed by flow cytometric assays of peripheral blood samples
Time frame: Throughout study
Multiparameter flow cytometric analyses of dendritic and NK cells in PBMCs, analysis of cytokines and chemokines using a multiplex assay of serum, plasma, semen, cervical secretions and dried blood spots, and gene expression analysis of RNA from PBMCs.
Time frame: Throughout study
Flow cytometric analysis of T-cell activation and subsets detected in specimens collected from the rectum, semen, or cervix
Time frame: Throughout study
Adenovirus-specific T-cell response rates detected in specimens collected from the rectum, semen, or cervix as assessed by IFN-γ ELISpot assay and/or flow cytometry
Time frame: Throughout study
HIV-specific IgA and IgG responses in saliva, cervical secretions, semen, which may include neutralizing activity
Time frame: Throughout study
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.
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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.
Janine Maenza study chair
Fred Hutchinson Cancer Center
1 site 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-HIVDNA-016-00-VP and VRCHIVADV014-00-VP in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 22 inclusion and 37 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 1 site 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. 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?
HIV-specific T-cell response rates detected in specimens collected from the rectum, semen, or cervix as assessed by IFN-γ ELISpot assay and/or flow cytometry (time frame: Throughout study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.