Safety of and Immune Response to a DNA Vaccine and a Recombinant HIV-1-MVA Vaccine, Separately and in Combination, in Healthy Adults

NCT ID: NCT00428337

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

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2008-08-31

Brief Summary

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The purpose of this study is to determine the safety of and immune response to two experimental vaccines, designed for use in combination, for the prevention of HIV infection in healthy adults.

Detailed Description

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The worldwide HIV/AIDS epidemic may only be controlled through the development of a safe and effective vaccine that will prevent HIV infection. DNA-based vaccines alone promote a weak immune response but when used as priming immunogens, followed by a recombinant viral vaccine that is a very attenuated vaccinia (smallpox) vaccine presenting the same immunogens as a booster, immunization with such a combination regimen seems to induce much stronger responses. EP-1233 is a DNA-HIV-recombinant vaccine designed to interact with CD4 (helper-inducer) and CD8 (cytotoxic) T lymphocytes (T cells) to prime CD4 and CD8 cells to respond to HIV components. MVA-mBN32 is a HIV-recombinant viral (MVA) vaccine that through other ways of interacting with CD4 and CD8 cells to immunize (boost) with similar HIV immunogens, may result in a stronger immune response.

The purpose of this study is to determine the safety of and immune response to two experimental vaccines for the prevention of HIV infection, individually and in combination, in healthy adults who have not been previously vaccinated against smallpox. Participants will be randomly assigned to one of three groups. All participants will receive injections at Days 0, 28, 84, and 168 of the study. Participants assigned to Group 1 will receive, on Day 0, one injection in each arm of EP-1233 or placebo and the same study product (EP-1233 or the DNA placebo) on Day 28. Thereafter, each Group 1 participant will receive one injection of MVA-mBN32 or placebo on Days 84 and 168. Groups 2 and 3 will not begin enrollment until safety and immunogenicity data from Group 1 have been evaluated. Participants assigned to Group 2 will receive only the DNA vaccine EP-1233 (or placebo) in each arm on all injection days. Participants in Group 3 will not begin enrollment until safety and immunogenicity data from Group 1 have been evaluated. Participants assigned to Group 3 will receive a consistent regimen of MVA-mBN32 (or placebo) on all injection days. Participants will be required to keep a symptom log for 3 days after each injection and attend clinical visits on Day 0, 14, 28, 42, 84, 98, 168, 182, 273, and 364 of the study. At each of the 10 visits, a physical exam, cardiac assessment, and HIV risk reduction and prevention counseling will occur. Blood collection will occur on Days 0, 14, 42, 98, 182, 273, and 364. Urine collection will occur on Days 14, 42, 98, and 182.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

Participants will receive one injection of DNA vaccine EP-1233 or placebo in each shoulder on Days 0 and 28 and one injection of MVA-mBN32 or placebo in each arm on Days 84 and 168

Group Type EXPERIMENTAL

EP-1233

Intervention Type BIOLOGICAL

DNA-HIV-recombinant vaccine

MVA-mBN32

Intervention Type BIOLOGICAL

HIV-recombinant viral vaccine

2

Participants will receive one injection of DNA vaccine EP-1233 or placebo in each shoulder on Days 0, 28, 84, and 168

Group Type EXPERIMENTAL

EP-1233

Intervention Type BIOLOGICAL

DNA-HIV-recombinant vaccine

3

Participants will receive one injection of MVA-mBN32 or placebo in each arm on Days 0, 28, 84, and 168

Group Type EXPERIMENTAL

MVA-mBN32

Intervention Type BIOLOGICAL

HIV-recombinant viral vaccine

Interventions

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EP-1233

DNA-HIV-recombinant vaccine

Intervention Type BIOLOGICAL

MVA-mBN32

HIV-recombinant viral vaccine

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Good general health

Exclusion Criteria

* Previous receipt of smallpox vaccination
* HIV-infected
* Hepatitis B surface antigen positive
* Participation in prior HIV vaccination trial
* Immunosuppressive medications within 168 days prior to study entry
* Receipt of blood products within 120 days of study entry
* Receipt of live attenuated, medically indicated subunit, or killed (inactivated) vaccines within 30 days of study entry
* Certain abnormal lab values
* Pregnant or breastfeeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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HIV Vaccine Trials Network

NETWORK

Sponsor Role collaborator

Pharmexa-Epimmune

UNKNOWN

Sponsor Role collaborator

Bavarian Nordic

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geoffrey Gorse

Role: STUDY_CHAIR

Saint Louis University School of Medicine

Christine Mhorag Hay

Role: STUDY_CHAIR

University of Rochester

Locations

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San Francisco Vaccine and Prevention CRS

San Francisco, California, United States

Site Status

Univ. of Rochester HVTN CRS

Rochester, New York, United States

Site Status

Vanderbilt Vaccine CRS

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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Dale CJ, Thomson S, De Rose R, Ranasinghe C, Medveczky CJ, Pamungkas J, Boyle DB, Ramshaw IA, Kent SJ. Prime-boost strategies in DNA vaccines. Methods Mol Med. 2006;127:171-97. doi: 10.1385/1-59745-168-1:171.

Reference Type BACKGROUND
PMID: 16988455 (View on PubMed)

Ostrowski MA, Yu Q, Yue FY, Liu J, Jones B, Gu XX, Loutfy M, Kovacs CM, Halpenny R. Why can't the immune system control HIV-1? Defining HIV-1-specific CD4+ T cell immunity in order to develop strategies to enhance viral immunity. Immunol Res. 2006;35(1-2):89-102. doi: 10.1385/IR:35:1:89.

Reference Type BACKGROUND
PMID: 17003512 (View on PubMed)

Rodriguez-Chavez IR, Allen M, Hill EL, Sheets RL, Pensiero M, Bradac JA, D'Souza MP. Current advances and challenges in HIV-1 vaccines. Curr HIV/AIDS Rep. 2006 Feb;3(1):39-47. doi: 10.1007/s11904-006-0007-0.

Reference Type BACKGROUND
PMID: 16522258 (View on PubMed)

Elizaga ML, Vasan S, Marovich MA, Sato AH, Lawrence DN, Chaitman BR, Frey SE, Keefer MC; MVA Cardiac Safety Working Group. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review. PLoS One. 2013;8(1):e54407. doi: 10.1371/journal.pone.0054407. Epub 2013 Jan 17.

Reference Type DERIVED
PMID: 23349878 (View on PubMed)

Other Identifiers

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10394

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 067

Identifier Type: -

Identifier Source: org_study_id