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HIV InfectionsPhase 1/2NCT03560258

HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) Vaccine Study

A Phase 1/2 study testing p24CE1/2 pDNA vaccine, p24CE1/2 pDNA vaccine admixed with full-length p55^gag pDNA vaccine and Full-length p55^gag pDNA vaccine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

This study evaluated the safety, immunogenicity, and preliminary assessment of efficacy of a novel vaccine encoding conserved elements (CE) of the HIV-1 Gag core protein, p24Gag, as a therapeutic vaccine in HIV-1 infected persons who were on antiretroviral therapy (ART). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV Infections
What is being tested?
p24CE1/2 pDNA vaccine, p24CE1/2 pDNA vaccine admixed with full-length p55^gag pDNA vaccine and Full-length p55^gag pDNA vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
15 sitesin 2 countries
Study dates
26 Mar 2019to 10 Feb 2021
Phase
Phase 1/2
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

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA assay. NOTE: The term "licensed" refers to a U.S. FDA-approved kit, which is required for all IND studies. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
  • Receiving a stable ART regimen for a minimum of 2 years prior to study entry and with no changes in the components of their antiretroviral therapy for at least 90 days prior to study entry. One of the agents must include an integrase inhibitor, non-nucleoside reverse transcriptase inhibitors (NNRTI), or a boosted-protease inhibitor (PI). NOTE: Changes in the ART regimen for reasons other than virologic breakthrough during the 2-year period are acceptable.
  • CD4 cell count greater than 500 cells/mm^3 obtained within 60 days prior to study entry at any U.S. laboratory that has a CLIA certification or its equivalent.
  • Nadir CD4 cell count greater than 350 cells/mm^3. NOTE: Candidate recall or documentation is acceptable.
  • One documented plasma HIV-1 RNA that is below the limit of detection of an FDA-approved assay between 24 and 36 months prior to the screening HIV-1 RNA and/or one documented plasma HIV-1 RNA that is below the limit of detection of an FDA-approved assay between 12 and 24 months prior to the screening HIV-1 RNA, and one documented HIV-1 RNA that is below the limit of detection of an FDA-approved assay collected fewer than 12 months prior to the screening HIV-1 RNA (see the protocol).
  • NOTE: A single, unconfirmed plasma HIV-1 RNA above the limit of detection but less than 400 copies/mL is allowed if followed by an HIV-1 RNA below detectable limits, but not in the 6 months prior to screening.
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  • NOTE: One documented plasma HIV-1 RNA that is below the limit of detection between 24 and 36 months prior to the screening HIV-1 RNA and one between 12 and 24 months prior to the screening HIV-1 RNA are preferred. However, in cases where a plasma HIV-1 RNA is not available in one of these windows, but there has been uninterrupted ART during the window and suppressed HIV-1 RNA before and after the window, the participant may be enrolled.
  • Plasma HIV-1 RNA level that is below the limit of detection of an FDA-approved assay within 60 days prior to study entry.
  • The following laboratory values obtained within 60 days prior to entry by any U.S. laboratory that has a CLIA certification or its equivalent:
  • Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3
  • Hemoglobin greater than or equal to 10.0 g/dL for men and greater than or equal to 9.0 g/dL for women
  • Platelet count greater than or equal to 100,000/mm^3
  • Prothrombin time (PT), partial thromboplastin time (PTT), and INR less than 1.5 x upper limit of normal (ULN)
  • Creatinine clearance greater than or equal to 50 mL/min estimated by the Cockcroft-Gault equation. NOTE: A program for calculating creatinine clearance by the Cockcroft-Gault method is available on www.fstrf.org.
  • Alanine aminotransferase (ALT) (SGPT) less than or equal to 2.5 x ULN
  • Total bilirubin less than 1.6 x ULN (if on atazanavir less than or equal to 5 x ULN)
  • HCV antibody negative result within 60 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result prior to study entry.
  • Negative HBsAg result obtained within 60 days prior to study entry.
  • Documentation of the availability of the stored pre-entry peripheral blood mononuclear cell (PBMC) specimens for T cell assays. Sites must receive confirmation from the processing lab via phone, e-mail, or fax that specimens have been entered into the ACTG Laboratory Data Management System (LDMS).
  • Ability and willingness of participant or legal guardian/representative to provide informed consent
  • Ability and willingness of participant to continue cART throughout the study.
  • For females of reproductive potential, negative serum or urine pregnancy test within 15 days prior to entry by any clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test. NOTE: Reproductive potential is defined as girls who have reached menarche and women who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) greater than or equal to 40 IU/mL or 24 consecutive months if an FSH is not available, or have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy).
  • If participating in sexual activity that could lead to pregnancy, willingness of female participants to use two forms of effective contraception while receiving study medication and for 3 months after stopping study medication is required.
  • NOTE A: Effective forms of contraception include:
  • Barrier methods (condoms [male or female] with or without a spermicidal agent, diaphragm, or cervical cap [with spermicide])
  • Hormone-based contraception (oral, patch, parenteral, implants, or vaginal ring)
  • Intrauterine device (IUD)
  • NOTE B: If the female participant is not of reproductive potential (women who are post-menopausal as defined above, or women who have undergone surgical sterilization [e.g., hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy]), she is eligible without requiring the use of a contraceptive method. Acceptable documentation of surgical sterilization and menopause is participant-reported history.
  • Indication of willingness to have the leukapheresis procedure. NOTE: Until 60 days after the last participating site is activated, each site will be limited to three participants in screening/enrollment at any given time. During this time period, these first three participants at each site will be required to agree at the screening visit to undergo the leukaphereses at the pre-entry and week 26 timepoints. Once the 60 day period after the last participating site is activated has passed, and at least 50% of the target accrual has agreed to undergo the leukaphereses, a study participant agreeing to the leukaphereses will be optional but highly recommended. The study team will inform the participating sites when this leukapheresis-optional period has begun.

Who cannot join

  • History of malignancy within the last 5 years prior to study entry or current malignancy requiring cytotoxic therapy. NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary.
  • History of HIV-related opportunistic infections within the last 5 years prior to study entry. NOTE: The CDC classifications are available on the A5369 protocol-specific webpage (PSWP).
  • History of or active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, autoimmune thyroiditis, or sarcoidosis. NOTE: For questions related to the definition of autoimmune disorders, sites should contact the A5369 core team per the Study Management section.
  • Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate IM injection.
  • A skin-fold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (on the medial deltoid or vastus lateralis muscles) that exceeds 50 mm. NOTE: The skin-fold measurement must be conducted in accordance with the procedure described in the TDS-IM Instructions for Use (see A5369 MOPS).
  • Use of any prior HIV vaccine (prophylactic and/or therapeutic) within 1 year prior to study entry. NOTE: A documented study placebo recipient may participate.
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  • Use of any investigational treatment within 6 months prior to study entry.
  • Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) within 4 weeks prior to study entry. NOTE: Participants with anticipated need to receive non-HIV vaccinations within 2 weeks prior to the scheduled study vaccination #2 (week 4), or #3 (week 12), or #4 (week 24) injection should be excluded.
  • Use of any infusion blood product or immune globulin within 3 months prior to study entry.
  • Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 30 days prior to entry.
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry. NOTE: Participants receiving stable physiologic glucocorticoid doses, defined as prednisone less than or equal to 10 mg/day or the equivalent, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids will not be excluded.
  • Intent to use immunomodulators (e.g., IL-2, IL-12, interferons, or TNF modifiers) during the course of the study.
  • Known or suspected hypersensitivity to any vaccine component, including hypersensitivity to amide-type local anesthetics, such as lidocaine (Xylocaine), mepivacaine (Polocaine/Carbocaine), etidocaine (Duranest), bupivacaine (Marcaine), or prilocaine.
  • Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.
  • History of cardiac arrhythmia or palpitations (e.g., supraventricular tachycardia, atrial fibrillation, frequent ectopy, or sinus bradycardia [i.e., less than 50 beats per minute on exam]) prior to study entry. NOTE: Sinus arrhythmia is not excluded.
  • History of syncope or fainting episode within 1 year of study entry.
  • Seizure disorder or any history of prior seizure.
  • Extensive tattoos covering the site of administration (upper left and right medial deltoid muscles and left and right vastus lateralis muscles).
  • Presence of any surgical or traumatic metal implants at the site of administration (medial deltoid or vastus lateralis muscles).
  • Immune deficiency other than HIV.
  • Breastfeeding or pregnancy.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Current HCV antiviral therapy.
  • Type I or type II diabetes mellitus.
  • Weight less than 50 kg or greater than 200 kg.
  • Known to have been started on antiretroviral therapy within 3 months of the presumed or known date of first acquiring HIV-1 infection; i.e., treated during acute HIV-1 infection.

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • Alabama CRS

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital CRS (MGH CRS)

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

    Boston, Massachusetts, 02115

  • Chapel Hill CRS

    Chapel Hill, North Carolina, 27599

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Rush University CRS

    Chicago, Illinois, 60612

  • Ohio State University CRS

    Columbus, Ohio, 43210

  • UCLA CARE Center CRS

    Los Angeles, California, 90035

  • Vanderbilt Therapeutics (VT) CRS

    Nashville, Tennessee, 37204

  • Penn Therapeutics, CRS

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh CRS

    Pittsburgh, Pennsylvania, 15213

  • University of Rochester Adult HIV Therapeutic Strategies Network CRS

    Rochester, New York, 14642

  • Ucsf Hiv/Aids Crs

    San Francisco, California, 94110

  • University of Washington AIDS CRS

    Seattle, Washington, 98104-9929

Other trials in United States

Puerto Rico1 site

  • Puerto Rico AIDS Clinical Trials Unit CRS

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-Infected Persons With Viral Suppression on Antiretroviral Therapy

This study evaluated the safety, immunogenicity, and preliminary assessment of efficacy of a novel vaccine encoding conserved elements (CE) of the HIV-1 Gag core protein, p24Gag, as a therapeutic vaccine in HIV-1 infected persons who were on antiretroviral therapy (ART). The study aimed to induce potent virus-specific cytotoxic T lymphocytes (CTL) responses.

Read the detailed description

This study evaluated the safety, immunogenicity, and preliminary assessment of efficacy of a novel vaccine encoding conserved elements (CE) of the HIV-1 Gag core protein, p24Gag, as a therapeutic vaccine in HIV-1 infected persons who were on antiretroviral therapy (ART).

The study randomly assigned participants to one of three groups. Participants in Arm 1 received p24CE1/2 pDNA vaccine at Weeks 0 and 4, followed by p24CE1/2 pDNA admixed with full-length p55^gag pDNA vaccine at Weeks 12 and 24. Participants in Arm 2 received full-length p55^gag pDNA vaccine at Weeks 0, 4, 12, and 24. Participants in Arm 3 received placebo at Weeks 0, 4, 12, and 24.

Study visits occurred at Weeks 0, 4, 6, 12, 24, 26, and 48 and included physical examinations and blood and urine collection. Some participants underwent leukapheresis and stool sample collection.

Conditions
HIV Infections
Being tested
p24CE1/2 pDNA vaccine, p24CE1/2 pDNA vaccine admixed with full-length p55^gag pDNA vaccine, Full-length p55^gag pDNA vaccine, Placebo
Keywords
Therapeutic Vaccination
Medical subject headings
HIV Infections

What participants receive

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

  • p24CE1/2 pDNA vaccineBiological

    4 mg administered by one injection/electroporation

  • p24CE1/2 pDNA vaccine admixed with full-length p55^gag pDNA vaccineBiological

    2 mg p24CE1/2 pDNA admixed with 2 mg full-length p55^gag pDNA administered by one injection/electroporation

  • Full-length p55^gag pDNA vaccineBiological

    4 mg full-length p55^gag pDNA vaccine administered by one injection/electroporation

  • PlaceboBiological

    1 mL placebo administered by one injection/electroporation

Study groups in NCT03560258
Study groupRoleWhat they receive
Arm A: p24CE/full-length Gag DNAExperimentalParticipants received p24CE1/2 pDNA vaccine at Weeks 0 and 4, followed by p24CE1/2 pDNA admixed with full-length p55^gag pDNA vaccine at Weeks 12 and 24.
Receives: Biological: p24CE1/2 pDNA vaccine; Biological: p24CE1/2 pDNA vaccine admixed with full-length p55^gag pDNA vaccine
Arm B: Full-length Gag DNAExperimentalParticipants received full-length p55^gag pDNA vaccine at Weeks 0, 4, 12, and 24.
Receives: Biological: Full-length p55^gag pDNA vaccine
Arm C: PlaceboPlacebo comparatorParticipants received placebo at Weeks 0, 4, 12, and 24.
Receives: Biological: Placebo

What is being measured

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

  1. Change in the Number of Conserved Elements (CEs) With a CD4 or a CD8 T Cell Response From Week 0 to Week 26

    Conserved elements (CEs) are regions of the HIV-1 p24Gag protein that rarely mutate. Seven such regions were considered in this study. At week 0 and at week 26, the CD4 cells and CD8 cells were tested to see whether they responded to each of these gene sequences. The number of regions which caused a CD4 or a CD8 response was counted. Then the difference was calculated: the number of CEs causing a response at week 26 minus the number of CEs causing a response at week 0.

    Measured: week 0 and week 26

  2. Occurrence of at Least One Greater Than or Equal to Grade 3 Adverse Event (AE) That Was Possibly, Probably, or Definitely Related to Study Treatment.

    Injection site pain or tenderness of less than 48 hours duration was not considered as primary safety outcome; Grade 4 AEs and deaths at any time on study were considered as primary safety outcomes. Sites referred to the DAIDS AE Grading Table, corrected Version 2.1, July 2017, to grade AEs. The relationship to study treatment was judged by the core team, blinded to treatment arm.

    Measured: Measured from treatment initiation through Week 48

Secondary outcomes (4)

  1. Change in the Number of CEs With a CD4 T Cell Response From Week 0 to Week 26

    Conserved elements (CEs) are regions of the HIV-1 p24Gag protein that rarely mutate. Seven such regions were considered in this study. At week 0 and at week 26, the CD4 cells were tested to see whether they responded to each of these gene sequences. The number of regions which caused a CD4 response was counted. Then the difference was calculated: the number of CEs causing a response at week 26 minus the number of CEs causing a response at week 0.

    Measured: week 0 and week 26

  2. Change in the Number of CEs With a CD8 T Cell Response From Week 0 to Week 26

    Conserved elements (CEs) are regions of the HIV-1 p24Gag protein that rarely mutate. Seven such regions were considered in this study. At week 0 and at week 26, the CD8 cells were tested to see whether they responded to each of these gene sequences. The number of regions which caused a CD8 response was counted. Then the difference was calculated: the number of CEs causing a response at week 26 minus the number of CEs causing a response at week 0.

    Measured: week 0 and week 26

  3. Change in the Magnitude of HIV-1 Specific CD4 T Cell Responses From Week 0 to Week 26.

    The HIV-1 specific CD4 T-cell responses were assessed by the intracellular cytokine staining (ICS) assay from peripheral blood mononuclear cell (PBMC) specimens obtained at week 0 and week 26. The magnitude of CD4 T cell responses was the percentage of CD4 T cells expressing cytokine IFNγ+ or IL2.

    Measured: week 0 and week 26

  4. Change in the Magnitude of HIV-1 Specific CD8 T Cell Responses From Week 0 to Week 26.

    The HIV-1 specific CD8 T-cell responses were assessed by the intracellular cytokine staining (ICS) assay from peripheral blood mononuclear cell (PBMC) specimens obtained at week 0 and week 26. The magnitude of CD8 T cell responses was the percentage of CD8 T cells expressing cytokine IFNγ+ or IL2.

    Measured: week 0 and week 26

Timeline

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

  1. First posted18 Jun 2018
  2. Study start26 Mar 2019
  3. Primary completion10 Feb 2021
  4. Study completion10 Feb 2021

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03560258
Sponsor's protocol ID
ACTG A5369
Other IDs
38398
Status last verified
Mar 2022
First submitted
6 Jun 2018
Last updated
26 Apr 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie results in the publication, after deidentification.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing p24CE1/2 pDNA vaccine, p24CE1/2 pDNA vaccine admixed with full-length p55^gag pDNA vaccine and Full-length p55^gag pDNA vaccine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in 2 countries.

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 26 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 26 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Puerto Rico. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 26 Apr 2022). 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?

Change in the Number of Conserved Elements (CEs) With a CD4 or a CD8 T Cell Response From Week 0 to Week 26 (time frame: week 0 and week 26). The study lists 2 primary outcomes in all. 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 NCT03560258.

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 26 Apr 2022.

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