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

NCT ID: NCT00801697

Last Updated: 2021-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

192 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2015-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

One of the more promising approaches in the development of a preventive HIV vaccine uses a DNA plasmid to prime the immune response to an adenoviral vector boost. This primary purpose of this study is to evaluate the safety, tolerability, and immune response to recombinant adenoviral serotype 35 (rAd35) and serotype 5 (rAD5) HIV-1 vaccines in Ad-5 naive and Ad-5 exposed HIV-uninfected adults.

This study will last approximately 12 months. Participants will include those who are both rAD5-naive and rAD5-exposed and will be stratified into one of four groups. Each group will consist of two arms, one interventional and one control. Participants in Groups 1, 2, and 3 will be rAD5-naive. Participants in Group 4 will be rAD5-exposed.

Participants in Group 1 will receive an injection of rAD35 vaccine or placebo at study entry and an injection of rAD5 vaccine or placebo at Month 6 with nine follow-up visits through Month 12. Participants in Groups 2, 3, and 4 will injections of DNA vaccinations or placebo at study entry and at Months 1 and 2, and an injection of rAD35 vaccine, rAD5 vaccine, or placebo at Month 6 with twelve follow-up visits though Month 12. A physical, questionnaire, and counseling will occur at all visits. Blood and urine collection will occur at most visits. A rectal swab will occur at selected visits. For females, a pregnancy test will occur at all visits.

Participants will be contacted for safety follow-ups after the injection every year for 5 years. Health and adverse events will be recorded. Participants will not need to return to the study clinic unless HIV confirmatory testing is needed.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1A

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

Group Type EXPERIMENTAL

rAd35

Intervention Type BIOLOGICAL

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

rAd5

Intervention Type BIOLOGICAL

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

1B

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

Group Type PLACEBO_COMPARATOR

rAd35 placebo

Intervention Type BIOLOGICAL

1 mL VRC-PBSPLA043-00-0VP

rAd5 placebo

Intervention Type BIOLOGICAL

1 mL VRC-DILUENT013-DIL-VP

2A

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

Group Type EXPERIMENTAL

DNA Vaccine

Intervention Type BIOLOGICAL

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

rAd5

Intervention Type BIOLOGICAL

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

2B

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

Group Type PLACEBO_COMPARATOR

DNA Vaccine placebo

Intervention Type BIOLOGICAL

1 mL VRC-PBSPLA043-00-VP

rAd5 placebo

Intervention Type BIOLOGICAL

1 mL VRC-DILUENT013-DIL-VP

3A

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

Group Type EXPERIMENTAL

DNA Vaccine

Intervention Type BIOLOGICAL

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

rAd35

Intervention Type BIOLOGICAL

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

3B

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

Group Type PLACEBO_COMPARATOR

DNA Vaccine placebo

Intervention Type BIOLOGICAL

1 mL VRC-PBSPLA043-00-VP

rAd35 placebo

Intervention Type BIOLOGICAL

1 mL VRC-PBSPLA043-00-0VP

4A

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

Group Type EXPERIMENTAL

DNA Vaccine

Intervention Type BIOLOGICAL

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

rAd35

Intervention Type BIOLOGICAL

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

4B

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

Group Type PLACEBO_COMPARATOR

DNA Vaccine placebo

Intervention Type BIOLOGICAL

1 mL VRC-PBSPLA043-00-VP

rAd35 placebo

Intervention Type BIOLOGICAL

1 mL VRC-PBSPLA043-00-0VP

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

DNA Vaccine

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

Intervention Type BIOLOGICAL

DNA Vaccine placebo

1 mL VRC-PBSPLA043-00-VP

Intervention Type BIOLOGICAL

rAd35

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

Intervention Type BIOLOGICAL

rAd35 placebo

1 mL VRC-PBSPLA043-00-0VP

Intervention Type BIOLOGICAL

rAd5

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

Intervention Type BIOLOGICAL

rAd5 placebo

1 mL VRC-DILUENT013-DIL-VP

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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
* Immunodeficiency
* Active Syphilis infection within the past 6 months
* Asthma. More information on this criterion can be found in the protocol.
* Diabetes mellitus
* Thyroidectomy or thyroid disease requiring medication during the last 12 months
* Hypertension. More information on this criterion can be found in the protocol.
* Body mass index greater than 35 or 40. More information on this criterion can be found in the protocol.
* Bleeding disorder
* Malignancy
* Seizure disorder
* Asplenia
* Psychiatric condition that precludes compliance with the protocol
* Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the study
* Pregnant or breastfeeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

HIV Vaccine Trials Network

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jonathan Fuchs, MD, MPH

Role: STUDY_CHAIR

SFDPH/UCSF

Pierre-Alexandre Bart, MD

Role: STUDY_CHAIR

CHUV (Lausanne)

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Alabama CRS

Birmingham, Alabama, United States

Site Status

Bridge HIV CRS

San Francisco, California, United States

Site Status

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, United States

Site Status

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

Boston, Massachusetts, United States

Site Status

Fenway Health (FH) CRS

Boston, Massachusetts, United States

Site Status

Columbia P&S CRS

New York, New York, United States

Site Status

New York Blood Center CRS

New York, New York, United States

Site Status

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, United States

Site Status

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, United States

Site Status

Seattle Vaccine and Prevention CRS

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 19012954 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18433307 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18830892 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34843602 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

10702

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 077

Identifier Type: -

Identifier Source: org_study_id