Evaluating the Safety and Priming Response of an HIV Vaccine Regimen in Healthy, HIV-Uninfected Adults
A Phase 1 Double Blind Placebo-controlled Clinical Trial to Evaluate the Safety and to Compare the Priming Ability of NYVAC Alone Versus NYVAC + AIDSVAX® B/E, and DNA Alone Versus DNA + AIDSVAX® B/E When Followed by NYVAC + AIDSVAX® B/E Boosts in Healthy, HIV-1-uninfected Adult Participants
1 other identifier
interventional
96
1 country
1
Brief Summary
This study will evaluate the safety of and the body's immune response to experimental HIV vaccine regimens using different vaccine priming combination, and boosting with the vaccines NYVAC and AIDSVAX® B/E.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 hiv-infections
Started Aug 2012
Typical duration for phase_1 hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2012
CompletedFirst Submitted
Initial submission to the registry
February 22, 2013
CompletedFirst Posted
Study publicly available on registry
February 27, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2014
CompletedMarch 25, 2015
March 1, 2015
2.3 years
February 22, 2013
March 23, 2015
Conditions
Outcome Measures
Primary Outcomes (3)
To evaluate the safety and tolerability of i) NYVAC prime with and without AIDSVAX® B/E plus NYVAC + AIDSVAX® B/E boosts; ii) DNA prime with and without AIDSVAX® B/E plus NYVAC + AIDSVAX® B/E boosts;
Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and serious adverse events. Signs and symptoms include pain, tenderness, and redness.
7 days
To evaluate and compare the body's immune response to 4 prime-boost regimens, comparing between: • NYVAC and NYVAC/AIDSVAX® B/E primes (Group 1 versus 2) • DNA and DNA/AIDSVAX® B/E primes (Group 3 versus 4)
HIV-specific binding antibody response as assessed by laboratory assay 2 weeks after the fourth vaccination
182 days
To evaluate and compare the durability of antibody response to different priming regimens when followed by two doses of NYVAC/AIDSVAX® B/E: • NYVAC and NYVAC/AIDSVAX® B/E primes (Group 1 versus 2) • DNA and DNA/AIDSVAX® B/E primes (Group 3 versus 4)
HIV-specific antibody response as assessed at multiple timepoints between 2 weeks and 12 months after the last boost
Days 182, 196, 273, 364, 455, 545
Secondary Outcomes (4)
To evaluate and compare the body's immune response to priming regimens, comparing between: • NYVAC and NYVAC/AIDSVAX® B/E primes (Group 1 versus 2) • DNA and DNA/AIDSVAX® B/E primes (Group 3 versus 4)
Day 42
To evaluate the body's immune response to different priming regimens when followed by two doses of NYVAC/AIDSVAX® B/E, comparing between: • Group 1 versus 2 • Group 3 versus 4 • Group 1 versus 3 • Group 2 versus 4
Days 98 and 196
To evaluate how long the immune response lasts in all 4 groups
Day 364
To evaluate the immune response to the 4 priming regimens
Day 42
Study Arms (4)
NYVAC Prime / NYVAC + AIDSVAX® B/E Boost vs. Placebo
OTHERThis arm will evaluate the safety of and the body's immune response to a vaccine regimen consisting of a NYVAC vaccine prime and NYVAC + AIDSVAX® B/E boost. Twenty participants will get vaccines and 4 will get only placebos.
NYVAC + AIDSVAX® B/E Prime / Boost vs. placebo
OTHERThis arm will evaluate the safety of and the body's immune response to a vaccine regimen consisting of priming and boosting with the vaccines NYVAC + AIDSVAX® B/E. Twenty participants will receive the vaccines and 4 will receive placebos. This arm will also be compared to arm 1 to see if the priming makes a difference in the body's immune response.
DNA prime + NYVAC + AIDSVAX® B/E Boost vs. placebo
OTHERThis arm will evaluate the safety of and the body's immune response to a vaccine regimen consisting of a DNA vaccine priming and NYVAC + AIDSVAX® B/E boosting. Twenty participants will receive the vaccines and 4 will receive placebos. This arm will also be compared to arm 4 to see if the priming makes a difference in the body's immune response.
DNA+AIDSVAX® B/E prime / NYVAC+AIDSVAX® B/E boost vs. placebo
OTHERThis arm will evaluate the safety of and the body's immune response to a vaccine regimen consisting of a DNA vaccine + AIDSVAX® B/E priming and NYVAC + AIDSVAX® B/E boosting. Twenty participants will receive the vaccines and 4 will receive placebos. This arm will also be compared to arm 3 to see if the priming makes a difference in the body's immune response.
Interventions
4 mg of DNA encoding clade C ZM96 Gag and gp140, CN54 Pol-Nef, administered intramuscularly (IM)
(along with NYVAC-HIV-PT4); ≥ 5x106 PFU encoding clade C ZM96 gp140 and ZM96 Gag and CN54 Pol-Nef, administered IM
(along with NYVAC-HIV-PT1); ≥ 5x106 PFU encoding clade C ZM96 gp140 and ZM96 Gag and CN54 Pol-Nef, administered IM
300mcg of subtype B (MN) HIV gp120 glycoprotein and 300mcg of subtype E (A244) HIV gp120 glycoprotein absorbed onto 600mcg of aluminum hydroxide gel adjuvant, administered IM.
Sodium Chloride for injection, 0.9% administered IM
600 mcg of aluminum hydroxide adjuvant, administered IM
Eligibility Criteria
You may qualify if:
- Age of 18 to 50 years
- Access to a 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: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- Willing to be contacted annually after completion of scheduled clinic visits for a total of 5 years following initial study injection.
- Agrees not to enroll in another study of an investigational research agent
- Good general health as shown by medical history, physical exam, and screening laboratory tests
- Willingness to receive HIV test results
- Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
- Assessed by the clinic staff as being at "low risk" for HIV infection
- Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male
- White blood cell count = 3,300 to 12,000 cells/mm3
- Total lymphocyte count ≥ 800 cells/mm3
- Remaining differential either within institutional normal range or with site physician approval
- Platelets = 125,000 to 550,000/mm3
- +19 more criteria
You may not qualify if:
- Blood products received within 120 days before first vaccination
- 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 HVTN 096/EV04 study
- Pregnant or breastfeeding
- HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 096/EV04 PSRT will determine eligibility on a case-by-case basis.
- Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 096/EV04 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 096/EV04 PSRT on a case-by-case basis.
- Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
- Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
- Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
- Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses \< 2 mg/kg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment.
- Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)
- Immunoglobulin received within 60 days before first vaccination
- Autoimmune disease
- Immunodeficiency
- Untreated or incompletely treated syphilis infection
- +40 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
HVTN Clinical Research Site (HVTN CRS) ,
Lausanne, 1011, Switzerland
Related Publications (3)
Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.
PMID: 40190112DERIVEDPantaleo G, Janes H, Karuna S, Grant S, Ouedraogo GL, Allen M, Tomaras GD, Frahm N, Montefiori DC, Ferrari G, Ding S, Lee C, Robb ML, Esteban M, Wagner R, Bart PA, Rettby N, McElrath MJ, Gilbert PB, Kublin JG, Corey L; NIAID HIV Vaccine Trials Network. Safety and immunogenicity of a multivalent HIV vaccine comprising envelope protein with either DNA or NYVAC vectors (HVTN 096): a phase 1b, double-blind, placebo-controlled trial. Lancet HIV. 2019 Nov;6(11):e737-e749. doi: 10.1016/S2352-3018(19)30262-0. Epub 2019 Oct 7.
PMID: 31601541DERIVEDHuang Y, Zhang L, Janes H, Frahm N, Isaacs A, Kim JH, Montefiori D, McElrath MJ, Tomaras GD, Gilbert PB. Predictors of durable immune responses six months after the last vaccination in preventive HIV vaccine trials. Vaccine. 2017 Feb 22;35(8):1184-1193. doi: 10.1016/j.vaccine.2016.09.053. Epub 2017 Jan 25.
PMID: 28131393DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Giuseppe Pantaleo, MD
Centre Hospitalier Universitaire Vaudois Hospices (CHUV)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 22, 2013
First Posted
February 27, 2013
Study Start
August 1, 2012
Primary Completion
December 1, 2014
Study Completion
December 1, 2014
Last Updated
March 25, 2015
Record last verified: 2015-03