Safety of and Immune Response to an HIV Preventive Vaccine (HIV-1 Gag DNA Alone or With IL-15 DNA) Given With or Without 2 Different Booster Vaccinations in HIV Uninfected Adults

NCT ID: NCT00115960

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

120 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2008-07-31

Brief Summary

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The purpose of this study is to determine the safety of and immune response to an experimental HIV vaccine, HIV-1 gag DNA, with and without an IL-15 DNA adjuvant (at escalating doses of 100, 500, and 1500 mcg). This study will also test the safety of and immune response to the HIV-1 gag DNA vaccine plus IL-15 DNA adjuvant given with or without 2 other adjuvant-containing booster vaccines.

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 2-part study will determine the safety and immunogenicity of the experimental HIV vaccine HIV-1 gag DNA with or without IL-15 adjuvant, boosted with either the HIV-1 gag DNA and IL-15 adjuvant vaccine or the HIV-1 gag DNA and IL-12 adjuvant vaccine.

There are two parts to this study. Part A will last 12 months. In Part A, 48 participants will be randomly assigned to 1 of 4 groups in sequential order (dose escalation). All participants will receive 3 vaccinations. Group 1 will receive 3 vaccinations of the HIV-1 gag DNA vaccine or placebo. Group 2 will receive 3 vaccinations of either the HIV-1 gag DNA vaccine with a low dose of IL-15 adjuvant or a placebo. Group 3 will receive 3 vaccinations of either the HIV-1 gag vaccine with a medium dose of IL-15 adjuvant or a placebo. Group 4 will receive 3 vaccinations of either the HIV-1 gag vaccine with a high dose of IL-15 adjuvant or a placebo. Vaccinations will be given at Months 0, 1, and 3. There will be 11 study visits in Part A. A physical exam, pregnancy prevention counseling, medication history, and adverse event reporting will occur at most visits. Urine and blood collection will occur at some visits. Participants will also be asked to complete questionnaires at certain visits.

Part B will last 15 months. In Part B, 72 participants will be randomly assigned to 1 of 2 groups. All Part B participants will receive 5 vaccinations. Group 5 will receive 5 vaccinations of either the HIV-1 gag vaccine plus IL-15 DNA or placebo; the vaccinations will occur at Months 0, 1, 3, 6, and 9. Group 7 will receive 3 vaccinations of the HIV-1 gag vaccine with a high dose of IL-15 adjuvant (maximum tolerated dose from Part A) followed by 2 vaccinations of the gag DNA vaccine with IL-12 DNA adjuvant. Some participants will receive placebo instead of this vaccine regimen. For Group 7, the HIV-1 gag vaccine with IL-15 adjuvant vaccinations will be given at Months 0, 1, and 3, and booster vaccinations will be given at Months 6 and 9. There will be 13 study visits in Part B. A physical exam, pregnancy prevention counseling, medication history, and adverse event reporting will occur at most visits. Urine and blood collection will occur at some visits. Participants will also be asked to complete questionnaires at certain visits.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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1

Group 1 will receive 3 vaccinations of the HIV-1 gag DNA vaccine, or placebo. Vaccinations will be given at Months 0, 1, and 3.

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

DNA vaccine containing the HIV gene gag

2

Group 2 will receive 3 vaccinations of either the HIV-1 gag DNA vaccine with a low dose of IL-15 adjuvant, or a placebo. Vaccinations will be given at Months 0, 1, and 3.

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

DNA vaccine containing the HIV gene gag

IL-15 DNA adjuvant

Intervention Type BIOLOGICAL

Cytokine injection

3

Group 3 will receive 3 vaccinations of either the HIV-1 gag vaccine with a medium dose of IL-15 adjuvant, or a placebo. Vaccinations will be given at Months 0, 1, and 3.

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

DNA vaccine containing the HIV gene gag

IL-15 DNA adjuvant

Intervention Type BIOLOGICAL

Cytokine injection

4

Group 4 will receive 3 vaccinations of either the HIV-1 gag vaccine with a high dose of IL-15 adjuvant, or a placebo. Vaccinations will be given at Months 0, 1, and 3.

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

DNA vaccine containing the HIV gene gag

IL-15 DNA adjuvant

Intervention Type BIOLOGICAL

Cytokine injection

5

In Part B, Group 5 will receive 5 vaccinations of either the HIV-1 gag vaccine plus IL-15 DNA, or placebo. Vaccinations will occur at Months 0, 1, 3, 6, and 9.

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

DNA vaccine containing the HIV gene gag

IL-15 DNA adjuvant

Intervention Type BIOLOGICAL

Cytokine injection

7

In Part B, Group 7 will receive 3 vaccinations of the HIV-1 gag vaccine with a high dose of IL-15 adjuvant (maximum tolerated dose from Part A) followed by 2 vaccinations of the gag DNA vaccine with IL-12 DNA adjuvant. Some participants will receive placebo instead of this vaccine regimen. For Group 7, the HIV-1 gag vaccine with IL-15 adjuvant vaccinations will be given at Months 0, 1, and 3, and booster vaccinations will be given at Months 6 and 9.

Group Type EXPERIMENTAL

HIV-1 gag DNA

Intervention Type BIOLOGICAL

DNA vaccine containing the HIV gene gag

IL-15 DNA adjuvant

Intervention Type BIOLOGICAL

Cytokine injection

IL-12 DNA adjuvant

Intervention Type BIOLOGICAL

Cytokine injection

Interventions

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HIV-1 gag DNA

DNA vaccine containing the HIV gene gag

Intervention Type BIOLOGICAL

IL-15 DNA adjuvant

Cytokine injection

Intervention Type BIOLOGICAL

IL-12 DNA adjuvant

Cytokine injection

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

Exclusion Criteria

* HIV vaccines in prior HIV vaccine trial
* Immunosuppressive medications within 168 days prior to first vaccination
* Blood products within 120 days prior to first vaccination
* Immunoglobulin within 60 days prior to first vaccination
* Live attenuated vaccines within 30 days prior to first vaccination
* Investigational research agents within 30 days prior to first vaccination
* Medically indicated subunit or killed vaccines within 14 days prior to first study vaccine administration, or allergy treatment with antigen injections within 30 days prior to first vaccination
* Current tuberculosis (TB) prophylaxis or therapy
* Clinically significant medical condition, physical exam findings, abnormal laboratory results, or past medical history with clinically significant implications for current health
* Any medical, psychiatric, or social condition that, in the opinion of the investigator, may interfere with the study
* Any occupational or other responsibility that, in the opinion of the investigator, may interfere with the study
* Diagnosis of allergy to amide-type local anesthetics
* Serious adverse reaction to vaccines, including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, or abdominal pain. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
* Autoimmune disease or immunodeficiency
* Unstable asthma
* Diabetes mellitus Type 1 or Type 2. Participants with histories of isolated gestational diabetes are not excluded.
* Thyroid disease requiring treatment in the past 12 months
* Serious angioedema within the last 3 years
* Uncontrolled hypertension
* Body mass index (BMI) of 40 or greater OR BMI of 35 or greater, when certain other 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.
* Seizure disorder requiring medication within the past 3 years
* Absence of the spleen
* Psychiatric condition, including psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years
* Pregnant or breastfeeding, or plan to become pregnant during the study


* Diagnosis of allergy to egg products
* Diagnosis of allergy 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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Lindsey Baden, MD

Role: STUDY_CHAIR

Harvard University

Xia Jin, MD, PhD

Role: STUDY_CHAIR

University of Rochester

Locations

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Brigham and Women's Hosp. CRS

Boston, Massachusetts, United States

Site Status

NY Blood Ctr./Union Square CRS

New York, New York, United States

Site Status

HIV Prevention & Treatment CRS

New York, New York, United States

Site Status

Univ. of Rochester HVTN CRS

Rochester, New York, United States

Site Status

NY Blood Ctr./Bronx CRS

The Bronx, New York, United States

Site Status

Miriam Hospital's HVTU

Providence, Rhode Island, United States

Site Status

Sao Paulo HVTU - CRT DST/AIDS CRS

São Paulo, , Brazil

Site Status

Countries

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United States Brazil

References

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Boyer JD, Chattergoon M, Muthumani K, Kudchodkar S, Kim J, Bagarazzi M, Pavlakis G, Sekaly R, Weiner DB. Next generation DNA vaccines for HIV-1. J Liposome Res. 2002 Feb-May;12(1-2):137-42. doi: 10.1081/lpr-120004786.

Reference Type BACKGROUND
PMID: 12604047 (View on PubMed)

Stratov I, DeRose R, Purcell DF, Kent SJ. Vaccines and vaccine strategies against HIV. Curr Drug Targets. 2004 Jan;5(1):71-88. doi: 10.2174/1389450043490686.

Reference Type BACKGROUND
PMID: 14738219 (View on PubMed)

Xin KQ, Hamajima K, Sasaki S, Tsuji T, Watabe S, Okada E, Okuda K. IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA vaccine. Vaccine. 1999 Feb 26;17(7-8):858-66. doi: 10.1016/s0264-410x(98)00271-0.

Reference Type BACKGROUND
PMID: 10067692 (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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10058

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 063

Identifier Type: -

Identifier Source: org_study_id