Evaluating the Immune Response to a rAd5 HIV Vaccine Administered in Three Different Ways in Healthy, HIV-Uninfected Adults

NCT01479296 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 08510796
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to evaluate the immune response to the Vaccine Research Center (VRC) rAd5 HIV vaccine when the vaccine components are administered in three different ways, in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Number of recognized epitopes as measured by enzyme-linked immunospot (ELISpot)

  Measured at 4 weeks following vaccination

• Total magnitude of gene-specific CD4 and CD8 T-cell responses as measured by intracellular cytokine staining (ICS)

  Measured at 4 weeks following vaccination

Secondary Outcomes (7)

• Total vaccine-specific CD4 and CD8 T-cell responses as measured by ICS

  Measured at 4 weeks following vaccination

• Total vaccine-specific CD4 and CD8 T-cell responses as measured by ICS

  Measured at 28 weeks following vaccination

• Polyfunctional CD4 and CD8 T-cell responses across one and multiple antigenic components of VRC rAd5 HIV vaccine as measured by ICS

  Measured at 28 weeks following vaccination

• Antibody binding to HIV epitopes by multiplex binding antibody assay and/or peptide array

  Measured at 28 weeks following vaccination

• Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, adverse events (AEs), and serious adverse events (SAEs) reported on an expedited basis to the Division of AIDS (DAIDS)

  Measured at 28 weeks following vaccination

Study Arms (3)

Group 1: rAd5 Plus Placebo

EXPERIMENTAL

Participants will receive the VRC rAd5 gag-pol/env A/B/C vaccine injection in their right arm (1×10\^10 PU), and placebo vaccine injections in their left arm, right thigh, and left thigh.

Biological: VRC rAd5 vaccine (rAd5 gag-pol/env A/B/C); Biological: Placebo Vaccine

Group 2: Separated Vaccine Components

EXPERIMENTAL

Participants will receive the rAd5 gag-pol vaccine injection in their right arm (0.5×10\^10 PU), the rAd5 env A vaccine injection in their left arm (0.17×10\^10 PU), the rAd5 env B vaccine injection in their right thigh (0.17×10\^10 PU), and the rAd5 env C vaccine injection in their left thigh (0.17×10\^10 PU).

Biological: rAd5 env A; Biological: rAd5 env B; Biological: rAd5 env C; Biological: rAd5 gag-pol

Group 3: Divided Dose rAd5

EXPERIMENTAL

Participants will receive the VRC rAd5 gag-pol/env A/B/C vaccine injection divided into fourths, with one fourth of the total dose given in each of 4 sites: right arm, left arm, right thigh, and left thigh (each at 0.25×10\^10 PU).

Biological: VRC rAd5 vaccine (rAd5 gag-pol/env A/B/C)

Interventions

VRC rAd5 vaccine (rAd5 gag-pol/env A/B/C) BIOLOGICAL

Given intramuscularly

Also known as: VRC-HIVADV014-00-VP

Group 1: rAd5 Plus Placebo; Group 3: Divided Dose rAd5

rAd5 env A BIOLOGICAL

Given intramuscularly

Also known as: VRC-HIVADV038-00-VP

Group 2: Separated Vaccine Components

rAd5 env B BIOLOGICAL

Given intramuscularly

Also known as: VRC-HIVADV052-00-VP

Group 2: Separated Vaccine Components

rAd5 env C BIOLOGICAL

Given intramuscularly

Also known as: VRC-HIVADV053-00-VP

Group 2: Separated Vaccine Components

rAd5 gag-pol BIOLOGICAL

Given intramuscularly

Also known as: VRC-HIVADV054-00-VP

Group 2: Separated Vaccine Components

Placebo Vaccine BIOLOGICAL

Given intramuscularly

Also known as: VRC-DILUENT013-DIL-VP

Group 1: rAd5 Plus Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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
• Demonstrates understanding of this study and that in a previous trial there was an association of increased acquisition of HIV with receipt of that study vaccine; completes a questionnaire prior to 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 exposure to HIV through the last required study visit
• Willing to be contacted annually after completion of scheduled clinic visits for a total of 5 years following initial study injection
• Agrees not to enroll in another study of an investigational research agent prior to completion of last required study 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" of HIV infection on the basis of sexual behaviors. More information on this criterion can be found in the protocol.
• Body weight greater than or equal to 110 lb (greater than or equal to 50 kg)
• Hemoglobin greater than or equal to 12.5 g/dL for participants who were born female; greater than or equal to 13.5 g/dL for participants who were born male
• White blood cell count between 3300 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 between 125,000 to 550,000/mm\^3

You may not qualify if:

• Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or any other use of illicit drugs within the 12 months prior to study entry
• History of newly acquired syphilis, gonorrhea, nongonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B within the 12 months prior to study entry
• 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 085 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the 5 years prior to study entry in a previous 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 085 PSRT will determine eligibility on a case-by-case basis. For potential participants who have received an experimental vaccine(s) more 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 nonchronic conditions not expected to recur \[length of therapy 10 days or less with completion at least 30 days prior to study entry\].)
• Blood products received within 120 days before the first vaccination
• Immunoglobulin received within 60 days before the first vaccination
• Live attenuated vaccines other than influenza vaccine received within 30 days before the first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to the first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before the first vaccination or that are scheduled within 14 days after the first vaccination
• Investigational research agents received within 30 days before the first vaccination
• Intent to participate in another study of an investigational research agent during the planned duration of the study
• Current anti-tuberculosis prophylaxis or therapy
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. More information on this criterion can be found in the protocol.

Sponsors & Collaborators

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

Study Sites (8)

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

UIC Project WISH CRS

Chicago, Illinois, 60612, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Related Publications (2)

• Appay V, Douek DC, Price DA. CD8+ T cell efficacy in vaccination and disease. Nat Med. 2008 Jun;14(6):623-8. doi: 10.1038/nm.f.1774.

  PMID: 18535580 BACKGROUND

• Vezys V, Yates A, Casey KA, Lanier G, Ahmed R, Antia R, Masopust D. Memory CD8 T-cell compartment grows in size with immunological experience. Nature. 2009 Jan 8;457(7226):196-9. doi: 10.1038/nature07486. Epub 2008 Nov 12.

  PMID: 19005468 BACKGROUND

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

Study Officials

• Ian Frank

  University of Pennsylvania

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2011
• First Posted: November 24, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: November 27, 2017
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (8)