Safety and Immune Response to Preventive HIV Immunization With Adenovirus Serotype 5 or 35 Vector

NCT00801697 | Completed Phase 1

• 2 other identifiers: HVTN 07710702
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 10

Brief Summary

This study will evaluate the safety and preliminary immune response to recombinant adenoviral serotype 35 and 5 HIV-1 vaccines in HIV-uninfected adults.

Conditions

HIV Infections

Keywords

HIV Seronegativity; HIV Preventive Vaccine; Adenovirus

Outcome Measures

Primary Outcomes (4)

• Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and expedited adverse events

  Throughout study

• Magnitude and frequency of immune responses between HIV-1 clade A env rAD35 and rAd5 vaccines when given as a boost after DNA vaccine

  At Week 4 following the fourth vaccination

• Magnitude and frequency of immune responses between clade A env rAD35 vaccine primed by Ad35 versus DNA

  At Week 4 following the last vaccination

• Magnitude and frequency of immune responses of HIV-1 clade A env rAD35 vaccine when given as a boost

  At Week 4 following the fourth vaccination

Secondary Outcomes (1)

• Immunogenicity of HIV-1 clade A env rAD35 vaccine given as a prime

  At Week 4 following the first vaccination

Study Arms (8)

1A

EXPERIMENTAL

rAD5-naive participants will receive rAd35 intramuscularly at study entry and rAd5 intramuscularly at Month 6

Biological: rAd35; Biological: rAd5

1B

PLACEBO COMPARATOR

Participants will receive rAd35 placebo intramuscularly at study entry and rAd5 placebo intramuscularly at Month 6

Biological: rAd35 placebo; Biological: rAd5 placebo

2A

EXPERIMENTAL

rAD5-naive participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd5 intramuscularly at Month 6

Biological: DNA Vaccine; Biological: rAd5

2B

PLACEBO COMPARATOR

Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd5 placebo intramuscularly at Month 6

Biological: DNA Vaccine placebo; Biological: rAd5 placebo

3A

EXPERIMENTAL

Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6

Biological: DNA Vaccine; Biological: rAd35

3B

PLACEBO COMPARATOR

Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6

Biological: DNA Vaccine placebo; Biological: rAd35 placebo

4A

EXPERIMENTAL

Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6

Biological: DNA Vaccine; Biological: rAd35

4B

PLACEBO COMPARATOR

Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6

Biological: DNA Vaccine placebo; Biological: rAd35 placebo

Interventions

DNA Vaccine BIOLOGICAL

4 mg VRC-HIVDNA044-00-VP administered as 1 mL

2A; 3A; 4A

DNA Vaccine placebo BIOLOGICAL

1 mL VRC-PBSPLA043-00-VP

2B; 3B; 4B

rAd35 BIOLOGICAL

VRC-HIVADV027-00-VP 1 x 10\^10 PU administered as 1 mL

1A; 3A; 4A

rAd35 placebo BIOLOGICAL

1 mL VRC-PBSPLA043-00-0VP

1B; 3B; 4B

rAd5 BIOLOGICAL

4 mg VRC-HIVADV038-00-VP administered as 1 mL

1A; 2A

rAd5 placebo BIOLOGICAL

1 mL VRC-DILUENT013-DIL-VP

1B; 2B

Eligibility Criteria

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

You may qualify if:

• Good general health
• Access to a participating HVTN clinical research site and willingness to be followed for the duration of the study
• Assessment of understanding, including understanding of Step Study results
• Willing to receive HIV test results
• Willing to discuss HIV infection risks, agree to HIV risk reduction counseling, and willing to continue 5 years of annual follow-up contact
• Willing to commit to maintaining behavior consistent with low risk of HIV exposure through the last required protocol visit
• Considered low risk for HIV infection after clinical staff assessment. More information on this criterion can be found in the protocol.
• Certain laboratory values. More information on this criterion can be found in the protocol.
• Negative Hepatitis B surface antigen
• Negative anti-Hepatitis C virus antibodies
• For females, agree to use effective contraception from at least 21 days prior to enrollment through the last protocol visit. More information on this criterion can be found in the protocol.

You may not qualify if:

• HIV-infected
• Active drug or alcohol abuse within 12 months prior to study entry
• History of newly acquired sexually transmitted infections. More information on this criterion can be found in the protocol.
• Experimental vaccines received within 5 years prior to study entry
• Immunosuppressive medications received within 168 days prior to first vaccination
• Blood products received within 120 days prior to first vaccination
• Immunoglobulin received within 60 days prior to first vaccination
• Live attenuated vaccines received within 30 days prior to first vaccination
• Investigational research agents received within 30 days prior to first vaccination
• Intent to participate in another study of an investigational research agent during planned duration of the study
• Any vaccines that not live attenuated vaccines and were received within 14 days prior to first vaccination
• Allergy treatment with antigen injections within 30 days prior to first vaccination or scheduled within 14 days after first vaccination
• Clinically significant medical condition, findings, results, or history with implications for current health. More information on this criterion can be found in the protocol.
• Serious adverse reactions to vaccines
• Autoimmune disease

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Vaccine Trials Network: collaborator

Study Sites (10)

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

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, 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

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Related Publications (4)

• Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN; Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 Nov 29;372(9653):1881-1893. doi: 10.1016/S0140-6736(08)61591-3. Epub 2008 Nov 13.

  PMID: 19012954 BACKGROUND

• Priddy FH, Brown D, Kublin J, Monahan K, Wright DP, Lalezari J, Santiago S, Marmor M, Lally M, Novak RM, Brown SJ, Kulkarni P, Dubey SA, Kierstead LS, Casimiro DR, Mogg R, DiNubile MJ, Shiver JW, Leavitt RY, Robertson MN, Mehrotra DV, Quirk E; Merck V520-016 Study Group. Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis. 2008 Jun 1;46(11):1769-81. doi: 10.1086/587993.

  PMID: 18433307 BACKGROUND

• Sheets RL, Stein J, Bailer RT, Koup RA, Andrews C, Nason M, He B, Koo E, Trotter H, Duffy C, Manetz TS, Gomez P. Biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (HIV-1), Ebola, or Marburg are similar despite differing adenovirus serotype vector, manufacturer's construct, or gene inserts. J Immunotoxicol. 2008 Jul;5(3):315-35. doi: 10.1080/15376510802312464.

  PMID: 18830892 BACKGROUND

• Fischinger S, Cizmeci D, Deng D, Grant SP, Frahm N, McElrath J, Fuchs J, Bart PA, Pantaleo G, Keefer M, O Hahn W, Rouphael N, Churchyard G, Moodie Z, Donastorg Y, Streeck H, Alter G. Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials. PLoS Pathog. 2021 Nov 29;17(11):e1010016. doi: 10.1371/journal.ppat.1010016. eCollection 2021 Nov.

  PMID: 34843602 DERIVED

MeSH Terms

Conditions

HIV Infections; Adenoviridae Infections

Interventions

Vaccines, DNA

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; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Antigens; Biological Factors

Study Officials

• Jonathan Fuchs, MD, MPH

  SFDPH/UCSF

  STUDY CHAIR

• Pierre-Alexandre Bart, MD

  CHUV (Lausanne)

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 2, 2008
• First Posted: December 3, 2008
• Study Start: February 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: April 1, 2015
• Last Updated: October 14, 2021

Record last verified: 2021-10

Locations

US (10)