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HIVPhase 1NCT01859325

Therapeutic Vaccine for HIV

A Phase 1 study testing rVSV, IL-12 pDNA adjuvant and HIV-Mag pDNA in people with HIV and Therapeutic Vaccine, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Background: 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV, Therapeutic Vaccine
What is being tested?
rVSV, IL-12 pDNA adjuvant and HIV-Mag pDNA
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
33 participants
Where
1 siteUnited States
Study dates
10 May 2013to 26 Feb 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 29Show fewer
  • Early HIV-1 Infection is defined as:
  • 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.
  • 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.

Who cannot join

  • Allergy to amide-type local anesthetics (bupivacaine (Marcaine), lidocaine (Xylocaine), Mepivacaine (Polocaine/Carbocaine), etidocaine (Duranest), prilocaine (Citanest, EMLA cream).
  • Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
  • Changes in cART regimen due to virologic breakthrough.
  • HIV immunotherapy or vaccine(s) received within 1 year prior to screening.
  • Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 4 weeks prior to study entry.
  • Interruption of cART for greater than 3 months since its initiation. 8. Any active malignancy that may require systemic chemotherapy or radiation therapy.
Show all 25Show fewer
  • Pregnancy or planned pregnancy during the study period or breastfeeding.
  • Any active malignancy that may require systemic chemotherapy or radiationtherapy.
  • Immunosuppressive medications received within 6 months before the first study vaccination (Not excluded: (1) corticosteroid nasal spray for allergic rhinitis; (2) topical corticosteroids for mild, uncomplicated dermatitis; or (3) oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur (length of therapy less than or equal to10 days, with completion in greater than or equal to 30 days prior to enrollment).
  • Evidence of hepatic decompensation in subjects with cirrhosis: history of ascites, hepatic encephalopathy, or bleeding esophageal varices, or screening laboratory results with any of the following:
  • 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.
  • History or other clinical evidence of:
  • 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.
  • Known allergy or sensitivity to the components of the investigational therapy.
  • History of significant cardiac arrhythmia (e.g., supraventricular tachycardia, ventricular tachycardia, and atrial fibrillation/flutter).
  • Active drug or alcohol use or any dependence other pattern of behaivor that, in the opinion of the investigator, would interfere with adherence to study requirements.
  • Any active systemic inflammatory or autoimmune disease or condition.
  • Presence of implanted electronic medical device (e.g., pacemaker, implantable cardiac defibrillator) or surgical/traumatic metal implant in the upper limb and/or upper torso.
  • Neurological or neuropsychiatric disorder that may interfere with the assessment of safety (e.g., frequent recurring headaches, for example, a pattern of greater than 1 headache/month affecting activities of daily living/work, frequent or severe/complicated migraines, cluster headaches); or history of encephalitis, narcolepsy, stroke with sequelae, moderate/severe major depressive disorder, moderate/severe bipolar disorder, seizure disorder.
  • Deltoid skinfold measurements (by caliper) of greater than 40 mm.
  • Body mass index greater than 40.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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

Background:

  • 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.
Read more

Objectives:

  • To see whether therapeutic vaccination is safe and can affect how the body responds to HIV infection.

Eligibility:

  • Individuals between 18 and 65 years of age who have HIV and are taking antiretroviral therapy drugs.

Design:

  • 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 studies.
Read the detailed description

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.

Being tested
rVSV, IL-12 pDNA adjuvant, HIV-Mag pDNA, Placebo
Keywords
HIV-MAG pDNA Prime, HIV Therapy, Therapeutic Vaccine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rVSVBiological

    Attenuated recombinant vesicular stomatitis virus containing HIV-1 gag gene

  • IL-12 pDNA adjuvantBiological

    plasmid DNA containing human IL-12 gene

  • HIV-Mag pDNABiological

    plasmid DNA vaccine containing genes encoding multiple HIV-1 proteins

  • PlaceboDrug

Study groups in NCT01859325
Study groupRoleWhat they receive
VaccineExperimentalHIV-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.
Receives: Biological: rVSV; Biological: IL-12 pDNA adjuvant; Biological: HIV-Mag pDNA
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Rate of Related Adverse Events in Subjects Who Began cART During Acute or Early HIV-1 Infection.

    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.

    Measured: 48 weeks

Secondary outcomes (1)
  1. HIV-1 Viral Load Following Antiretroviral Treatment Interruption (ATI).

    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.

    Measured: 72 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2013 (estimated)
  2. Study start10 May 2013
  3. Primary completion26 Feb 2017
  4. Study completion26 Feb 2017

Resources

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
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01859325
Sponsor's protocol ID
130141
Other IDs
13-I-0141
Status last verified
May 2018
First submitted
16 May 2013
Last updated
3 Mar 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Volberding PA, Deeks SG. Antiretroviral therapy and management of HIV infection. Lancet. 2010 Jul 3;376(9734):49-62. doi: 10.1016/S0140-6736(10)60676-9.

    PubMed 20609987
  • Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009 Mar 6;323(5919):1304-7. doi: 10.1126/science.1165706.

    PubMed 19265012
  • Trono D, Van Lint C, Rouzioux C, Verdin E, Barre-Sinoussi F, Chun TW, Chomont N. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science. 2010 Jul 9;329(5988):174-80. doi: 10.1126/science.1191047.

    PubMed 20616270
  • Sneller MC, Justement JS, Gittens KR, Petrone ME, Clarridge KE, Proschan MA, Kwan R, Shi V, Blazkova J, Refsland EW, Morris DE, Cohen KW, McElrath MJ, Xu R, Egan MA, Eldridge JH, Benko E, Kovacs C, Moir S, Chun TW, Fauci AS. A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection. Sci Transl Med. 2017 Dec 6;9(419):eaan8848. doi: 10.1126/scitranslmed.aan8848.

    PubMed 29212716

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rVSV, IL-12 pDNA adjuvant and HIV-Mag pDNA in people with HIV and Therapeutic Vaccine, 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 29 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 3 Mar 2020. 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. 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?

Yes. Results are posted in the registry (first posted 9 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Rate of Related Adverse Events in Subjects Who Began cART During Acute or Early HIV-1 Infection. (time frame: 48 weeks). 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 NCT01859325, which also lists 4 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 3 Mar 2020.

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