Evaluating the Safety of and Immune Response to HIV-MAG DNA Vaccine With or Without Plasmid IL-12 Adjuvant Delivered Intramuscularly Via Electroporation Followed by VSV-gag HIV Vaccine Boost in Healthy, HIV-Uninfected Adults
A Phase 1 Trial to Evaluate the Safety, Tolerability, and Immunogenicity of an IL-12 pDNA Enhanced HIV-1 Multiantigen pDNA Vaccine Delivered Intramuscularly With Electroporation, With an HIV-1 rVSV Vaccine Boost, in Healthy HIV-Uninfected Adult Participants
2 other identifiers
interventional
100
1 country
5
Brief Summary
Some vaccines may work better when given together with another substance known as an adjuvant or when given with an experimental procedure called electroporation (EP). EP is a method where an electric pulse is administered to the same muscle where the vaccine injection is given. The addition of the adjuvant to the vaccine and the delivery with EP may increase a person's immune response to the vaccine. Combination approaches such as a DNA vaccine followed by live vector boost may also increase a person's immune response to the vaccine components. All of these interventions will be tested in this study. This study will evaluate the safety and tolerability of and immune response to an HIV DNA vaccine with or without plasmid IL-12 adjuvant, when given by EP and followed by a live vector vaccine given IM by needle and syringe in healthy, HIV-uninfected adults.
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 May 2012
Longer than P75 for phase_1 hiv-infections
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 13, 2012
CompletedFirst Posted
Study publicly available on registry
April 17, 2012
CompletedStudy Start
First participant enrolled
May 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2016
CompletedOctober 15, 2021
October 1, 2021
2.3 years
April 13, 2012
October 13, 2021
Conditions
Outcome Measures
Primary Outcomes (7)
Frequency and severity of local injection/EP site reactogenicity signs and symptoms
Pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness
Measured through Month 12
Frequency and severity of systemic reactogenicity signs and symptoms
Fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms
Measured through Month 12
Magnitude of local injection/EP site pain as measured by a visual analog scale
Measured through Month 12
Frequency of adverse events (AEs) categorized by MedDRA body system, MedDRA preferred term, severity, and assessed relationship to study products
Detailed description of all AEs meeting DAIDS criteria for expedited reporting
Measured through Month 12
Distribution of values of safety laboratory measures
White blood cells, neutrophils, lymphocytes, hemoglobin, alkaline phosphatase, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and creatine phosphokinase (CPK) at baseline and at follow-up visits postvaccination
Measured through Month 12
Number of participants with early discontinuation of vaccinations and reason for discontinuation
Measured through Month 12
Distribution of responses to questions regarding acceptability of study injections procedures
Measured through Month 12
Secondary Outcomes (4)
Response rate of CD4 T-cell responses measured by intracellular cytokine staining (ICS) for IFN-γ and/or IL-2, to HIV potential T-cell epitope (PTE) peptide pools representing Gag, Pol, Env, Nef, Tat, and Vif
Measured through Month 12
Response rate of CD8 T-cell responses measured by ICS for IFN-γ and/or IL-2, to HIV PTE peptide pools representing Gag, Pol, Env, Nef, Tat, and Vif
Measured through Month 12
Response rate of T-cell responses as measured by IFN-γ enzyme-linked immunospot (ELISpot)
Measured through Month 12
Induction of binding antibodies to HIV-1 gag p55 and HIV-1 6101 env gp160
Measured through Month 12
Study Arms (8)
Group 1: Vaccine
EXPERIMENTALAt study entry and Months 1 and 3, participants will receive HIV-MAG vaccine administered as 0.5 mL by intramuscular (IM) injection in both the left and right deltoids using the Ichor Medical Systems TriGrid™ Delivery System (TDS) electroporation (EP) device. At Month 6, they will receive the VSV HIV gag vaccine by IM injection in both the left and right deltoids.
Group 1: Placebo
PLACEBO COMPARATORAt study entry and Months 1 and 3, participants will receive placebo administered as 0.5 mL by IM injection in both the left and right deltoids using the Ichor Medical Systems TDS EP device. At Month 6, they will receive placebo by IM injection in both the left and right deltoids.
Group 2: Vaccine
EXPERIMENTALAt study entry and Months 1 and 3, participants will receive HIV-MAG vaccine admixed with 250 mcg IL-12 pDNA adjuvant, and divided into two 0.55 mL IM injections administered in both the left and right deltoids using the Ichor Medical Systems TDS EP device. At Month 6, they will receive the VSV HIV gag vaccine by IM injection in both the left and right deltoids.
Group 2: Placebo
PLACEBO COMPARATORAt study entry and Months 1 and 3, participants will receive placebo administered as 0.55 mL by IM injection in both the left and right deltoids using the Ichor Medical Systems TDS EP device. At Month 6, they will receive placebo by IM injection in both the left and right deltoids.
Group 3: Vaccine
EXPERIMENTALAt study entry and Months 1 and 3, participants will receive HIV-MAG vaccine admixed with 1,000 mcg of the IL-12 pDNA adjuvant and divided into two 0.75 mL IM injections administered in both the left and right deltoids using the Ichor Medical Systems TDS EP device. At Month 6, they will receive the VSV HIV gag vaccine by IM injection in both the left and right deltoids.
Group 3: Placebo
PLACEBO COMPARATORAt study entry and Months 1 and 3, participants will receive placebo administered as 0.75 mL by IM injection in both the left and right deltoids using the Ichor Medical Systems TDS EP device. At Month 6, they will receive placebo by IM injection in both the left and right deltoids.
Group 4: Vaccine
EXPERIMENTALAt study entry and Months 1 and 3, participants will receive HIV-MAG vaccine admixed with 1500 mcg of the IL-12 pDNA adjuvant divided into two 0.9 mL IM injections administered in both the left and right deltoids using the Ichor Medical Systems TDS EP device. At Month 6, they will receive the VSV HIV gag vaccine by IM injection in both the left and right deltoids.
Group 4: Placebo
PLACEBO COMPARATORAt study entry and Months 1 and 3, participants will receive placebo administered as 0.9 mL by IM injection in both the left and right deltoids using the Ichor Medical Systems TDS EP device. At Month 6, they will receive placebo by IM injection in both the left and right deltoids.
Interventions
Participants assigned to receive the HIV-MAG vaccine will receive 3 mg of the vaccine with bupivacaine, alone or admixed with one of three doses of the IL-12 pDNA adjuvant.
Participants assigned to receive the IL-12 plasmid (IL-12 pDNA) adjuvant will receive one of three doses (total of 250 mcg, 1000 mcg, or 1500 mcg) of the adjuvant admixed with the HIV-MAG vaccine.
Participants assigned to receive the VSV HIV gag vaccine will receive a total dose of 1x10\^8 plaque-forming units (PFUs) administered as 5x10\^7 PFU in 1 mL by IM injection in both the left and right deltoids at Month 6.
Placebo will consist of sodium chloride for injection, USP 0.9%.
The HIV-MAG vaccine, IL-12 pDNA adjuvant, and placebos for IL-12 pDNA adjuvant/HIV-MAG vaccines will be delivered IM into the deltoid by the Ichor Medical Systems TDS EP device.
Eligibility Criteria
You may qualify if:
- Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willing to be followed for the planned duration of the study
- Able and willing to provide informed consent
- Assessment of understanding: participant demonstrates understanding of this study and completes a questionnaire prior to the first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- Willing to receive HIV test results
- Willing 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
- Willing to be contacted annually after completion of scheduled clinic visits for a total of 3 years following initial study injection
- Agrees not to enroll in another study of an investigational research agent prior to completion of last required protocol clinic visit (excludes annual contacts for safety surveillance)
- In good general health as shown by medical history, physical exam, and screening laboratory tests
- Assessed by the clinic staff as being at "low risk" for HIV infection
- Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female; greater than or equal to 13.0 g/dL for participants who were born male
- White blood cell (WBC) count equal to 3,300 to 12,000 cells/mm\^3
- Total lymphocyte count greater than or equal to 800 cells/mm\^3
- Remaining differential either within institutional normal range or with site physician approval
- Platelets equal to 125,000 to 550,000/mm\^3
- Chemistry panel: ALT, AST, alkaline phosphatase, and creatinine values less than or equal to the institutional upper limits of normal; CPK less than or equal to 2.0 times the institutional upper limit of normal
- +10 more criteria
You may not qualify if:
- Allergy to amide-type local anesthetics (bupivacaine \[Marcaine\], lidocaine \[Xylocaine\], mepivacaine \[Polocaine/Carbocaine\], etidocaine \[Duranest\], prilocaine \[Citanest, EMLA® cream\])
- Presence of implanted electronic medical device (e.g., pacemaker, implantable cardioverter defibrillator)
- Presence of surgical or traumatic metal implant in the upper limb and/or upper torso
- Sinus bradycardia (defined as less than 50 bpm on exam) or a history of cardiac arrhythmia: e.g., supraventricular tachycardia, atrial fibrillation, or frequent ectopy
- Neurological or neuropsychiatric disorder that may interfere with the assessment of safety: e.g., frequent recurring headaches (i.e., a pattern of more than one headache per month affecting activities of daily living \[ADLs\]/work, frequent or severe/complicated migraines, cluster headaches), a chronic pain syndrome, dizziness, history of meningitis or encephalitis, cranial/spinal/peripheral neuropathy, limb weakness or paralysis, movement disorder, narcolepsy, stroke with sequelae, moderate/severe major depressive disorder, moderate/severe bipolar disorder
- Seizure disorder
- Untreated or incompletely treated syphilis infection
- 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 087 Protocol Safety Review Team (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 potential participants who have received control/placebo in an experimental vaccine trial, the HVTN 087 PSRT will determine eligibility on a case-by-case basis. For potential participants who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the PSRT on a case-by-case basis.
- Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray for allergic rhinitis; \[2\] topical corticosteroids for mild, uncomplicated dermatitis; or \[3\] oral/parenteral corticosteroids given for non-chronic conditions not expected to recur \[length of therapy 10 days or less with completion at least 30 days prior to enrollment\].)
- 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 injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
- 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 087 study
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Columbia P&S CRS
New York, New York, 10032-3732, United States
New York Blood Center CRS
New York, New York, 10065, United States
University of Rochester Vaccines to Prevent HIV Infection CRS
Rochester, New York, 14642, United States
Penn Prevention CRS
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, 37232-2582, United States
Related Publications (6)
Egan MA, Megati S, Roopchand V, Garcia-Hand D, Luckay A, Chong SY, Rosati M, Sackitey S, Weiner DB, Felber BK, Pavlakis GN, Israel ZR, Eldridge JH, Sidhu MK. Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice. Vaccine. 2006 May 22;24(21):4510-23. doi: 10.1016/j.vaccine.2005.08.024. Epub 2005 Aug 19.
PMID: 16140439BACKGROUNDDolter KE, Evans CF, Ellefsen B, Song J, Boente-Carrera M, Vittorino R, Rosenberg TJ, Hannaman D, Vasan S. Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation. Vaccine. 2011 Jan 17;29(4):795-803. doi: 10.1016/j.vaccine.2010.11.011. Epub 2010 Nov 19.
PMID: 21094270BACKGROUNDHirao LA, Wu L, Khan AS, Hokey DA, Yan J, Dai A, Betts MR, Draghia-Akli R, Weiner DB. Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques. Vaccine. 2008 Jun 13;26(25):3112-20. doi: 10.1016/j.vaccine.2008.02.036. Epub 2008 Mar 11.
PMID: 18430495BACKGROUNDJohnson JE, Coleman JW, Kalyan NK, Calderon P, Wright KJ, Obregon J, Ogin-Wilson E, Natuk RJ, Clarke DK, Udem SA, Cooper D, Hendry RM. In vivo biodistribution of a highly attenuated recombinant vesicular stomatitis virus expressing HIV-1 Gag following intramuscular, intranasal, or intravenous inoculation. Vaccine. 2009 May 14;27(22):2930-9. doi: 10.1016/j.vaccine.2009.03.006. Epub 2009 Mar 13.
PMID: 19428903BACKGROUNDElizaga ML, Li SS, Kochar NK, Wilson GJ, Allen MA, Tieu HVN, Frank I, Sobieszczyk ME, Cohen KW, Sanchez B, Latham TE, Clarke DK, Egan MA, Eldridge JH, Hannaman D, Xu R, Ota-Setlik A, McElrath MJ, Hay CM; NIAID HIV Vaccine Trials Network (HVTN) 087 Study Team. Safety and tolerability of HIV-1 multiantigen pDNA vaccine given with IL-12 plasmid DNA via electroporation, boosted with a recombinant vesicular stomatitis virus HIV Gag vaccine in healthy volunteers in a randomized, controlled clinical trial. PLoS One. 2018 Sep 20;13(9):e0202753. doi: 10.1371/journal.pone.0202753. eCollection 2018.
PMID: 30235286DERIVEDLi SS, Kochar NK, Elizaga M, Hay CM, Wilson GJ, Cohen KW, De Rosa SC, Xu R, Ota-Setlik A, Morris D, Finak G, Allen M, Tieu HV, Frank I, Sobieszczyk ME, Hannaman D, Gottardo R, Gilbert PB, Tomaras GD, Corey L, Clarke DK, Egan MA, Eldridge JH, McElrath MJ, Frahm N; NIAID HIV Vaccine Trials Network. DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8+ T-Cell Responses by Interleukin-12 Plasmid DNA. Clin Vaccine Immunol. 2017 Nov 6;24(11):e00263-17. doi: 10.1128/CVI.00263-17. Print 2017 Nov.
PMID: 28931520DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Christine (Mhorag) Hay
University of Rochester
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 13, 2012
First Posted
April 17, 2012
Study Start
May 1, 2012
Primary Completion
September 1, 2014
Study Completion
October 1, 2016
Last Updated
October 15, 2021
Record last verified: 2021-10