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

NCT03560258 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: ACTG A536938398
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 15

Brief 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). The study aimed to induce potent virus-specific cytotoxic T lymphocytes (CTL) responses.

Conditions

HIV Infections

Keywords

Therapeutic Vaccination

Outcome Measures

Primary Outcomes (2)

• 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.

  week 0 and week 26

• 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 from treatment initiation through Week 48

Secondary Outcomes (4)

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

  week 0 and week 26

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

  week 0 and week 26

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

  week 0 and week 26

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

  week 0 and week 26

Study Arms (3)

Arm A: p24CE/full-length Gag DNA

EXPERIMENTAL

Participants 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.

Biological: p24CE1/2 pDNA vaccine; Biological: p24CE1/2 pDNA vaccine admixed with full-length p55^gag pDNA vaccine

Arm B: Full-length Gag DNA

EXPERIMENTAL

Participants received full-length p55\^gag pDNA vaccine at Weeks 0, 4, 12, and 24.

Biological: Full-length p55^gag pDNA vaccine

Arm C: Placebo

PLACEBO COMPARATOR

Participants received placebo at Weeks 0, 4, 12, and 24.

Biological: Placebo

Interventions

p24CE1/2 pDNA vaccine BIOLOGICAL

4 mg administered by one injection/electroporation

Arm A: p24CE/full-length Gag DNA

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

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

Arm A: p24CE/full-length Gag DNA

Full-length p55^gag pDNA vaccine BIOLOGICAL

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

Arm B: Full-length Gag DNA

Placebo BIOLOGICAL

1 mL placebo administered by one injection/electroporation

Arm C: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (15)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush University CRS

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, July 2017
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Jeffrey M. Jacobson, MD

  School of Medicine at Case Western Reserve University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: June 18, 2018
• Study Start: March 26, 2019
• Primary Completion: February 10, 2021
• Study Completion: February 10, 2021
• Last Updated: April 26, 2022
• Results First Posted: April 26, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data."

Locations

US (14); PR (1)