Study of an HIV Preventive Vaccine Given With or Without an Adjuvant in HIV Uninfected Adults

NCT ID: NCT00111605

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

144 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2008-05-31

Brief Summary

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The purpose of this study is to evaluate the safety and tolerability of an experimental HIV vaccine. The vaccine will be given with or without IL-12 DNA adjuvant (at three escalating doses of 100, 500, and 1,500 mcg respectively), a substance that helps the body respond to a vaccine. This study will also determine the safety and tolerability of an experimental HIV vaccine boosted with two adjuvants.

Detailed Description

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The HIV epidemic is a major global health challenge, causing tremendous human suffering and economic loss throughout the world. The need for a safe, effective, and affordable HIV preventive vaccine is critical. This study will determine the safety and immunogenicity of an experimental HIV vaccine, HIV-1 gag DNA, given with or without an IL-12 adjuvant and boosted HIV-1 gag DNA with or without IL-12 DNA adjuvant.

This study will comprise two parts (Parts A and B). Part A will last 9 months and Part B, 15 months. Part A will consist of 48 participants enrolled in 4 groups. Group 1 participants will be randomly assigned to receive the gag DNA vaccine or placebo. Participants in Groups 2, 3, and 4 will be randomly assigned to receive the gag DNA vaccine and either 100 mcg, 500 mcg, or 1,500 mcg IL-12 DNA or placebo. Vaccinations for Groups 1 through 4 will be given intramuscularly and will occur at study entry and at Months 1 and 3.

Part B will consist of 96 participants, enrolled in 3 groups. Participants in Part B will receive their first vaccination 2 weeks after Part A participants receive their second vaccination. Group 5 participants will receive either the HIV-1 gag DNA vaccine or placebo. Group 6 participants will receive either the HIV-1 gag DNA vaccine plus IL-12 DNA or placebo. Vaccinations for Groups 5 and 6 will occur at study entry and at Months 1, 3, 6, and 9. Group 7 participants will receive either the gag DNA vaccine plus IL-12 DNA or placebo at study entry and at Months 1 and 3. Throughout the study, blood and urine collections will occur, physical exams will be conducted, HIV testing and counseling will be offered, and interviews and questionnaires will be completed.

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

TRIPLE

Participants Caregivers Investigators

Study Groups

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1

HIV gag DNA vaccine or placebo on Days 0, 28, and 84

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Sodium chloride injection (0.9%)

Intervention Type BIOLOGICAL

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

2

HIV gag DNA vaccine plus 100 mcg of IL-12 or placebo on Days 0, 28, and 84

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

HIV-1 gag DNA plus IL-12 DNA adjuvant

Intervention Type BIOLOGICAL

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Sodium chloride injection (0.9%)

Intervention Type BIOLOGICAL

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

3

HIV gag DNA vaccine plus 500 mcg of IL-12 or placebo on Days 0, 28, and 84

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

HIV-1 gag DNA plus IL-12 DNA adjuvant

Intervention Type BIOLOGICAL

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Sodium chloride injection (0.9%)

Intervention Type BIOLOGICAL

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

4

HIV gag DNA vaccine plus 1,500 mcg of IL-12 or placebo on Days 0, 28, and 84

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

HIV-1 gag DNA plus IL-12 DNA adjuvant

Intervention Type BIOLOGICAL

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Sodium chloride injection (0.9%)

Intervention Type BIOLOGICAL

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

5

HIV gag DNA vaccine or placebo on Days 0, 28, 84, 168, and 273

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Sodium chloride injection (0.9%)

Intervention Type BIOLOGICAL

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

6

HIV gag DNA vaccine plus IL-12 or placebo on Days 0, 28, and 84 plus CTL MEP/RC529-SE/GM-SCF booster vaccine on Days 168 and 273

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

HIV-1 gag DNA plus IL-12 DNA adjuvant

Intervention Type BIOLOGICAL

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

CTL MEP/RC529-SE/GM-CSF (CTL MEP vaccine)

Intervention Type BIOLOGICAL

A 1 mL intramuscular injection in the deltoid

Sodium chloride injection (0.9%)

Intervention Type BIOLOGICAL

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

7

HIV gag DNA vaccine plus IL-12 DNA adjuvant or placebo on Days 0 and 84

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Sodium chloride injection (0.9%)

Intervention Type BIOLOGICAL

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

Interventions

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HIV-1 gag DNA

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Intervention Type BIOLOGICAL

HIV-1 gag DNA plus IL-12 DNA adjuvant

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Intervention Type BIOLOGICAL

CTL MEP/RC529-SE/GM-CSF (CTL MEP vaccine)

A 1 mL intramuscular injection in the deltoid

Intervention Type BIOLOGICAL

Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* HIV uninfected
* Access to a participating HIV Vaccine Trials Unit (HVTU)
* Willing to receive HIV test results
* Willing and able to comply with all study requirements
* In good general health
* Willing to use acceptable methods of contraception for at least 21 days prior to study entry and until the last study visit. More information about this criterion can be found in the protocol.
* Hepatitis B surface antigen negative
* Anti-hepatitis C virus (anti-HCV) antibody negative or negative HCV PCR if anti-HCV antibody is positive
* Weighs of or greater than 110 pounds (50 kg)

Exclusion Criteria

* HIV infection
* HIV vaccines or placebos in prior HIV trial
* Immunosuppressive medications within 168 days prior to first study vaccination
* Blood products within 120 days prior to first study vaccination
* Live attenuated vaccines within 30 days prior to first study vaccination
* Medically indicated subunit or killed vaccines within 14 days prior to first study vaccination
* Pneumococcal vaccine within 14 days prior to first study vaccination
* Allergy treatment with antigen injections within 30 days prior to first study vaccination
* Current anti-tuberculosis (TB) preventive therapy or treatment
* Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health
* Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol.
* Any job-related responsibility that would interfere with the study
* Allergies to local amide-type anesthetics
* Serious adverse reactions to vaccines, including hypersensitivity and related symptoms. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
* Autoimmune disease or immunodeficiency
* Active syphilis infection. Participants who have been fully treated for syphilis over 6 months prior to study entry are not excluded.
* Moderate to severe asthma. More information on this criterion can be found in the protocol.
* Type 1 or type 2 diabetes mellitus. Participants with histories of isolated gestational diabetes are not excluded.
* Thyroid disease or surgical removal of the thyroid requiring medication during the 12 months prior to study entry
* Accumulation of fluid in the blood vessels (angioedema) within 3 years prior to study entry, with episodes requiring medication in the 2 years prior to study entry
* Hypertension that is not well controlled by medication OR blood pressure of 150/100 or higher at study entry
* Body mass index (BMI) of 40 or greater OR BMI of 35 or greater, if certain criteria are met. More information about these criteria can be found in the protocol.
* Bleeding disorder
* Cancer. Participants with surgically removed cancer that, in the opinion of the investigator, is unlikely to recur are not excluded.
* Absence of the spleen
* Plans to become pregnant during the study
* Pregnancy or breastfeeding

Exclusion Criterion for Participants in Part B:

* Allergies to yeast-derived products
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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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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Spyros Kalams, MD

Role: STUDY_CHAIR

Vanderbilt University

Scott Parker, MD

Role: STUDY_CHAIR

University of Alabama at Birmingham

Locations

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Alabama Vaccine CRS

Birmingham, Alabama, United States

Site Status

Project Brave HIV Vaccine CRS

Baltimore, Maryland, United States

Site Status

Vanderbilt Vaccine CRS

Nashville, Tennessee, United States

Site Status

Chiang Mai Univ. HVTN CRS

Chiang Mai, , Thailand

Site Status

Countries

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United States Thailand

References

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Bolesta E, Gzyl J, Wierzbicki A, Kmieciak D, Kowalczyk A, Kaneko Y, Srinivasan A, Kozbor D. Clustered epitopes within the Gag-Pol fusion protein DNA vaccine enhance immune responses and protection against challenge with recombinant vaccinia viruses expressing HIV-1 Gag and Pol antigens. Virology. 2005 Feb 20;332(2):467-79. doi: 10.1016/j.virol.2004.09.043.

Reference Type BACKGROUND
PMID: 15680412 (View on PubMed)

Letvin NL. Progress toward an HIV vaccine. Annu Rev Med. 2005;56:213-23. doi: 10.1146/annurev.med.54.101601.152349.

Reference Type BACKGROUND
PMID: 15660510 (View on PubMed)

Sha BE, Onorato M, Bartlett JA, Bosch RJ, Aga E, Nokta M, Adams EM, Li XD, Eldridge J, Pollard RB. Safety and immunogenicity of a polyvalent peptide C4-V3 HIV vaccine in conjunction with IL-12. AIDS. 2004 May 21;18(8):1203-6. doi: 10.1097/00002030-200405210-00015.

Reference Type BACKGROUND
PMID: 15166537 (View on PubMed)

Jin X, Morgan C, Yu X, DeRosa S, Tomaras GD, Montefiori DC, Kublin J, Corey L, Keefer MC; NIAID HIV Vaccine Trials Network. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials. Vaccine. 2015 May 11;33(20):2347-53. doi: 10.1016/j.vaccine.2015.03.036. Epub 2015 Mar 25.

Reference Type DERIVED
PMID: 25820067 (View on PubMed)

Kalams SA, Parker S, Jin X, Elizaga M, Metch B, Wang M, Hural J, Lubeck M, Eldridge J, Cardinali M, Blattner WA, Sobieszczyk M, Suriyanon V, Kalichman A, Weiner DB, Baden LR; NIAID HIV Vaccine Trials Network. Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults. PLoS One. 2012;7(1):e29231. doi: 10.1371/journal.pone.0029231. Epub 2012 Jan 5.

Reference Type DERIVED
PMID: 22242162 (View on PubMed)

Other Identifiers

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10057

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 060

Identifier Type: -

Identifier Source: org_study_id