Evaluating Heterologous-Insert Prime-Boost HIV Vaccine Regimens in HIV-Uninfected Adults

NCT01095224 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 08310783
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to evaluate the safety and immune response of an adenovirus-based HIV-1 vaccine regimen that includes two vaccines given at different time points in HIV-uninfected adults.

Conditions

HIV Infections

Keywords

HIV Preventive Vaccine

Outcome Measures

Primary Outcomes (7)

• Frequency and severity of local injection site reactogenicity signs and symptoms, including pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness

  Measured at baseline and Month 3

• Frequency and severity of systemic reactogenicity signs and symptoms, including fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms

  Measured at baseline and Month 3

• Frequency of adverse events (AEs) categorized by MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products; detailed description of all AEs meeting DAIDS criteria for expedited reporting

  Measured at Month 9

• Distribution of values of safety laboratory measures, including white blood cells (WBCs), neutrophils, lymphocytes, hemoglobin, platelets, and alanine aminotransferase (ALT) at baseline and at postvaccination follow-up study visits

  Measured at Month 9

• Number of participants with early discontinuation of vaccinations and reason for discontinuation

  Measured at Month 9

• Number of shared HIV epitopes targeted by T-cells

  Measured at 4 weeks following the final vaccination

• HIV-1-specific interferon gamma (IFN-y) ELISpot responses

  Measured at 4 weeks following the final vaccination

Secondary Outcomes (6)

• Number of shared HIV epitopes targeted by T-cells

  Measured at 4 weeks following the final vaccination

• HIV-1-specific IFN-y ELISpot responses

  Measured at 4 weeks following the final vaccination

• Frequency of insert-specific CD4 and CD8 cells

  Measured at 4 weeks following the final vaccination

• Number of HIV epitopes targeted by T-cells

  Measured at 4 weeks following the final vaccination

• Functional spectrum of CD4 and CD8 cells by intracellular cytokine staining (ICS) assay for IFN-y, IL-2, and TNF-a

  Measured at Month 9

Study Arms (5)

rAd35 Env A and rAd5 Env A

EXPERIMENTAL

Participants will receive the rAd35 Env A vaccine at baseline and the rAd5 Env A vaccine at Month 3.

Biological: rAd35 Env A; Biological: rAd5 Env A

rAd35 Env A and rAd5 Env B

EXPERIMENTAL

Participants will receive the rAd35 Env A vaccine at baseline and the rAd5 Env B vaccine at Month 3.

Biological: rAd35 Env A; Biological: rAd5 Env B

rAd35 Env A and rAd35 Env A

EXPERIMENTAL

Participants will receive the rAd35 Env A vaccine at baseline and at Month 3.

Biological: rAd35 Env A

rAd5 Env A and rAd5 Env A

EXPERIMENTAL

Participants will receive the rAd5 Env A vaccine at baseline and at Month 3.

Biological: rAd5 Env A

rAd5 Env A and rAd5 Env B

EXPERIMENTAL

Participants will receive the rAd5 Env A vaccine at baseline and the rAd5 Env B vaccine at Month 3.

Biological: rAd5 Env A; Biological: rAd5 Env B

Interventions

rAd35 Env A BIOLOGICAL

1 x 10\^10 particle units (PU) administered as 1 mL intramuscularly (IM) in deltoid

Also known as: VRC-HIVADV027-00-VP

rAd35 Env A and rAd35 Env A; rAd35 Env A and rAd5 Env A; rAd35 Env A and rAd5 Env B

rAd5 Env A BIOLOGICAL

1 x 10\^10 PU administered as 1 mL IM in deltoid

Also known as: VRC-HIVADV038-00-VP

rAd35 Env A and rAd5 Env A; rAd5 Env A and rAd5 Env A; rAd5 Env A and rAd5 Env B

rAd5 Env B BIOLOGICAL

1 x 10\^10 PU administered as 1 mL IM in deltoid

Also known as: VRC-HIVADV052-00-VP

rAd35 Env A and rAd5 Env B; rAd5 Env A and rAd5 Env B

Eligibility Criteria

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

You may qualify if:

• Assessed by clinic staff as being "low risk" for HIV infection
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willing to be followed for the duration of the study
• Able and willing to provide informed consent
• Assessment of understanding, including the completion of a questionnaire before the first vaccination and demonstration of understanding for all questionnaire items answered incorrectly
• Willing to receive HIV test results
• Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required study visit
• Willing to continue annual follow-up contact after the final study visit for a total of 5 years after study entry
• In good general health, as shown by medical history, physical exam, and screening laboratory tests
• Assessed by the clinic staff as having a low risk of HIV infection on the basis of sexual behaviors in the 12 months before study entry. More information on this criterion can be found in the protocol.
• Adenovirus 5 nAb titer less than 1:18
• Adenovirus 35 nAb titer less than 1:12
• Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female and greater than or equal to 13.0 g/dL for participants who were born male
• White blood cell (WBC) count between 3,300 to 12,000 cells/mm\^3
• Total lymphocyte count greater than or equal to 800 cells/mm\^3
• Remaining differential either within site's normal range or with site physician approval

You may not qualify if:

• Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs in the 12 months before study entry
• History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B in the 12 months before study entry
• Received non-HIV experimental vaccines in a previous vaccine trial in the 5 years before study entry
• Received HIV vaccines in a prior HIV vaccine trial
• Immunosuppressive medications received within 168 days before the first study vaccination
• Blood products received within 120 days before the first study vaccination
• Immunoglobulin received within 60 days before the first study vaccination
• Live attenuated vaccines received within 30 days before the first study vaccination or scheduled within 14 days after injection
• Investigational research agents received within 30 days before the first study vaccination
• Intent to participate in another investigational drug study
• Any vaccines that are not live attenuated vaccines and were received within 14 days before the first study vaccination
• Allergy treatment with antigen injections within 30 days before the first study vaccination or scheduled within 14 days after the first vaccination
• Current anti-tuberculosis (TB) prophylaxis or therapy
• Clinically significant medical condition, abnormal physical examination findings, clinically significant abnormal laboratory results, or past medical history that may affect current health
• Any medical, psychiatric, occupational, or other condition that would interfere with participation in the study

Sponsors & Collaborators

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

Study Sites (8)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, 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

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Related Publications (3)

• Vaine M, Lu S, Wang S. Progress on the induction of neutralizing antibodies against HIV type 1 (HIV-1). BioDrugs. 2009;23(3):137-53. doi: 10.2165/00063030-200923030-00001.

  PMID: 19627166 BACKGROUND

• 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

• Walsh SR, Moodie Z, Fiore-Gartland AJ, Morgan C, Wilck MB, Hammer SM, Buchbinder SP, Kalams SA, Goepfert PA, Mulligan MJ, Keefer MC, Baden LR, Swann EM, Grant S, Ahmed H, Li F, Hertz T, Self SG, Friedrich D, Frahm N, Liao HX, Montefiori DC, Tomaras GD, McElrath MJ, Hural J, Graham BS, Jin X; HVTN 083 Study Group and the NIAID HVTN. Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083. J Infect Dis. 2016 Feb 15;213(4):541-50. doi: 10.1093/infdis/jiv496. Epub 2015 Oct 15.

  PMID: 26475930 DERIVED

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

• Xia Jin, MD, PhD

  University of Rochester

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: March 30, 2010
• Study Start: September 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: February 1, 2016
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (8)