Therapeutic Vaccine for HIV
National Institute of Allergy and Infectious Diseases (NIAID)
Profectus BioSciences, Inc.
Information provided by (Responsible Party)
National Institutes of Health Clinical Center (CC)
First received: May 16, 2013
Last updated: March 9, 2018
Last Verified: March 2018
History of Changes
- In most people who have human immunodeficiency virus (HIV), the immune system cannot control or cure the infection. Antiretroviral therapy drugs can keep the amount of HIV virus low for a long time. However, this treatment does not remove the virus from the body. In the vast majority of patients antiretroviral therapy also will not protect the body from the virus once treatment stops. Researchers want to see if therapeutic vaccination can help people with HIV. Therapeutic vaccination means giving vaccines to treat an infection that someone already has (HIV, in this case). It may help the body's immune system attack the infection. This study will look at different measures of HIV infection after receiving either therapeutic vaccination or a placebo.
- To see whether therapeutic vaccination is safe and can affect how the body responds to HIV infection.
- Individuals between 18 and 65 years of age who have HIV and are taking antiretroviral therapy drugs.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- During the screening visit and throughout the study until week 56, participants will continue to take their HIV medications.
- Participants will be divided into two groups. One group will have the study vaccines. The other will have a placebo.
- The first study vaccine or placebo will be given in weeks 4, 12, and 36. The second study vaccine or the placebo will be given in weeks 24 and 48. Blood samples and other tests will be given at each visit.
- After the study visit at week 56, participants will stop their HIV medications until week 72. From weeks 58 through 72, they will come in every 2 weeks for study visits; each visit will take about 1 hour to complete. These visits will look at the body s response to the vaccines and their HIV viral load. After week 72, participants will re-start their HIV medications.
- There will be follow-up study visits from weeks 76 to 96, with blood tests and other
Biological : rVSV
Biological : IL-12 pDNA adjuvant
Biological : HIV-Mag pDNA
Drug : Placebo
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase I Randomized, Double-Blind, Placebo-Controlled Study of a Multi-Antigen DNA Vaccine Prime Delivered by In Vivo Electroporation, rVSV Booster Vaccine in HIV-Infected Patients Who Began Antiretroviral Therapy During Acute/Early Infection|
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures
The Rate of Related Adverse Events in Subjects Who Began cART During Acute or Early HIV-1 Infection.
[ Time Frame: 48 weeks ]
The rate of occurrence of grade 3 or higher AEs, including serious adverse events (SAEs) that per standard criteria (see safety section) are: At least possibly related to the test article, and Definitely NOT related to a factor other than the test article This is to evaluate safety and tolerability of the study vaccines.
- HIV-1 Viral Load Following Antiretroviral Treatment Interruption (ATI).
[ Time Frame: 72 weeks ]
The difference in HIV-1 viral load at the end of the ATI between the vaccine and placebo groups. Levels of plasma viremia in the vaccine and placebo groups were compared using the Wilcoxon rank sum test at the end of treatment interruption periods to determine the antiviral efficacy of the therapeutic vaccine regimen. The limit of detection of plasma viremia was 40 copies/ml of HIV RNA.
|Study Start Date:||May 10, 2013|
|Estimated Study Completion Date:||August 28, 2019|
|Estimated Primary Completion Date:||August 28, 2019 (Final data collection date for primary outcome measure)|
HIV-MAG pDNA vaccine prime will be administered at a dose of 3000 g (1500 g of the HIV-1 gag/pol plasmid and 1500 g of the HIV-1 net/tat/vif, env plasmid) at week 0, 4, 12, and 36. Each construct of HIV-MAG pDNA vaccine (1500 g each) will be mixed and combined with 1000 g of the IL-12 pDNA adjuvant. The resulting mixture will be divided into 2 IM injections and administered as 0.75 mL IM injection in the left deltoid and 0.75 mL IM injection in the right deltoid with EP using the TDS device. IL-12 pDNA adjuvant will be mixed with the HIV-MAG pDNA vaccine prime, as noted above, and administered at a dose of 1000 g (500 g in each IM injection) at week 0, 4, 12, and 36. rVSV HIV gag booster vaccine--The total dose, 1x107 pfu, will be administered as 1 mL (5x106 pfu) IM injection in the left deltoid and 1 mL (5x106 pfu) IM injection in the right deltoid at week 24 and 48.
Attenuated recombinant vesicular stomatitis virus containing HIV-1 gag gene
Biological: IL-12 pDNA adjuvant
plasmid DNA containing human IL-12 gene
Biological: HIV-Mag pDNA
plasmid DNA vaccine containing genes encoding multiple HIV-1 proteins
Placebo for the IL-12 pDNA adjuvant and HIV-MAG pDNA vaccine (sodium chloride for injection, USP 0.9%) will be administered as 0.75 mL IM injection in the left deltoid and 0.75 mL IM injection in the right deltoid at weeks 0, 4, 12, and 36 with EP using the TDS device. Placebo for the rVSV HIV gag (sodium chloride for injection, USP 0.9%) will be administered as 1 mL IM injection in the left deltoid and 1 mL IM injection in the right deltoid at week 24 and 48.
The advent of combination antiretroviral therapy (cART) has dramatically improved the
clinical outcome in human immunodeficiency virus (HIV)-infected individuals through sustained
reduction in viral replication. However, it has become clear that cART alone cannot eradicate
HIV in infected individuals, likely in part due to the persistence of viral reservoirs in
peripheral blood and various tissue compartments. Consequently, a major thrust of HIV
research over the past several years has been to develop therapeutic strategies that can
eliminate persistent viral reservoirs and boost host immunity to control viral replication
upon discontinuation of cART. Therapeutic HIV vaccination is one approach that could
potentially achieve these goals through vaccine-induced improvement in HIV-specific immune
responses and/or by direct reactivation of HIV-specific CD4+ memory T cells that harbor
latent HIV. An effective therapeutic vaccine could augment immunologic control of HIV
infection and potentially obviate the need for chronic cART.
The current study is an exploratory randomized, 2-arm (1:1), double-blind, placebo-controlled trial evaluating the safety and efficacy of an HIV-1 multiantigen plasmid DNA (HIV-MAG pDNA) vaccine prime in combination with an interleukin-12 plasmid DNA (IL-12 pDNA) adjuvant delivered by in vivo electroporation followed by a recombinant vesicular stomatitis virus vector containing the HIV-1 gag gene (rVSV HIV gag) booster vaccine in subjects on cART who started therapy during acute or early HIV infection.
Subjects will be randomized to receive placebo or the HIV-MAG pDNA (3000 g) vaccine prime and IL-12 pDNA adjuvant (1000 g) at week 0, 4, 12, and 36, and the rVSV HIV gag booster vaccine (1x107 plaque-forming units) at week 24 and 48. The HIV-MAG pDNA vaccine prime and IL-12 pDNA adjuvant will be administered as 2 IM injections, 1 into each deltoid, with electroporation using the Ichor TDS device, while the rVSV HIV gag booster vaccine will be administered as 2 conventional IM injections, 1 into each deltoid. After the week 56 visit, all subjects will undergo an analytical treatment interruption to determine if the vaccination strategy results in an improved immune control of viral replication, as evidenced by a blunted or absent rebound in HIV plasma viremia. All subjects will be followed through week 96 for safety and efficacy parameters.
The study population includes HIV-infected adults who began cART during acute or early infection. Subjects must be receiving an effective cART regimen, with a CD4 cell count of >450 cells/mm3 at screening, and they must have documented viral suppression below the limit of detection for greater than1 year. The rationale for testing the study vaccine regimen in this subject population is because these individuals may have a relatively preserved immune function, which could be augmented by therapeutic vaccination.
|Ages Eligible for Study:||18 Years to 65 Years|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- INCLUSION CRITERIA:
- Age, 18-65 years.
- Institution of cART within 12 weeks of being diagnosed with acute or early HIV-1 infection.
Acute HIV-1 infection is defined as:
- Detectable plasma HIV-1 RNA levels of greater than 2000 copies/mL with a negative result from an HIV-1 EIA, or
- Positive result from an HIV-1 EIA with a negative or indeterminate result from an HIV-1 western blot that subsequently evolves to a confirmed positive result, or
- Negative result from an HIV-1 EIA within the past 4 months and HIV-1 RNA levels of greater than 400,000 copies/mL, in the setting of a potential exposure to HIV-1.
- Negative result from an HIV-1 EIA within 6 months prior to a positive result from an HIV-1 EIA and an HIV-1 western blot.
- Negative result from a rapid HIV-1 test within 1 month prior to a positive result from an HIV-1 EIA and an HIV-1 western blot.
- Presence of low level of HIV antibodies as determined by having a positive EIA or a positive Western blot with a non-reactive detuned EIA according to a serologic testing algorithm for recent infection.
- CD4+ cell count greater than 450 cells/mm3 at screening.
- Documentation of continuous cART treatment with suppression of plasma viral level below the limit of detection for greater than 1 year. Subjects with a single blip (i.e., detectable viral levels on cART) prior to randomization may be included provided they satisfy the following criteria:
- The blips are less than 400 copies/mL, and
- Succeeding viral levels return to levels below the limit of detection on subsequent testing.
- Willingness to undergo ATI.
- Laboratory values within pre-defined limits at screening:
- Absolute neutrophil count greater than 1,000/mm3.
- Hemoglobin levels greater than 10.0 g/dL for men and greater than 9.0 g/dL for women.
- Platelet count greater than 100,000/mm3.
- Prothrombin time (PT) and partial thromboplastin time (PTT) less than 1.5 upper limit of normal (ULN).
- Estimated or a measured creatinine clearance rate of greater than 60 mL/min as determined by the NIH Clinical Center laboratory.
- AST and ALT levels of less than 2.5 x ULN. ~#o2~ Willingness to have samples stored for future research.
- Women of childbearing potential must have a negative pregnancy test result.
- They must agree to use an adequate form of contraception:
- Hormonal contraception.
- Male or female condoms with or without a spermicidal
- Diaphragm or cervical cap with a spermicidal.
- Intrauterine device.
- Exclusion Criteria:
Early HIV-1 Infection is defined as:
- International normalized ratio of greater than or equal to1.5 x ULN.
- Serum albumin less than 3.2 g/dL.
- Serum total bilirubin greater than 1.8 x ULN, unless history of Gilbert's disease or deemed related to treatment with atazanavir.
- Significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction, significant arrhythmia).
- Severe illness, malignancy, immunodeficiency other than HIV, or any other conditions that, in the opinion of the investigator, would make the subject unsuitable for the study.
- AIDS-defining condition.
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01859325
Locations Show More
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
Sponsors and CollaboratorsNational Institute of Allergy and Infectious Diseases (NIAID)
Profectus BioSciences, Inc.
|Principal Investigator:||Michael C Sneller, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|
Additional Information:NIH Clinical Center Detailed Web Page
|Responsible Party:||National Institute of Allergy and Infectious Diseases (NIAID)|
|ClinicalTrials.gov Identifier:||NCT01859325 History of Changes|
|Other Study ID Numbers:||130141|
|Study First Received:||May 16, 2013|
|Last Updated:||March 9, 2018|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Keywords provided by National Institutes of Health Clinical Center (CC):HIV-MAG pDNA Prime
Additional relevant MeSH terms:
ClinicalTrials.gov processed this data on April 26, 2018
This information is provided by ClinicalTrials.gov.