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Safety of and Immune Response to the Experimental Preventive HIV Vaccine, EP HIV-1090, in Healthy, HIV-1 Uninfected Adults

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
EP HIV-1043
EP HIV-1090
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV Seronegativity, HIV Preventive Vaccine

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Note: Groups 1, 2, 3, and 5 have permanently discontinued enrollment per the 12/26/06 letter of amendment. Inclusion Criteria: Good general health Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed for the duration of the study Willing to receive HIV test results Have understanding of the study Willing to use acceptable forms of contraception Negative pregnancy test Exclusion Criteria: HIV vaccines in a 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 prophylaxis or therapy 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 Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded. Autoimmune disease or immunodeficiency Active syphilis infection unless the participant has completed full treatment for syphilis 6 months prior to enrollment Unstable asthma Diabetes mellitus type 1 or 2 Thyroid disease or thyroidectomy requiring treatment Serious angioedema within 3 years prior to enrollment Uncontrolled hypertension Body mass index (BMI) of 40 or greater BMI of 35 or greater if the participant is older than 45 years, has systolic blood pressure greater than 140 mm Hg, has diastolic blood pressure greater than 90 mm Hg, smokes, or has known hyperlipidemia Bleeding disorder Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period Seizure disorder requiring medication within the 3 years prior to enrollment Absence of the spleen Mental illness that would interfere with the study Other conditions that, in the judgment of the investigator, would interfere with the study Pregnancy, breastfeeding, or plans to become pregnant

Sites / Locations

  • San Francisco Vaccine and Prevention CRS
  • Project Brave HIV Vaccine CRS
  • Univ. of Rochester HVTN CRS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

5

Arm Description

Group 1 will receive 4 vaccinations of the EP-1043 vaccine or placebo. Vaccinations will be given at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.

Group 2 will receive 4 vaccinations of the EP-1043 vaccine or placebo. Vaccinations will be given at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.

In Part B, Group 3 will receive 4 vaccinations of either the EP-1043 vaccine or placebo. Vaccinations will occur at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.

In Part B, Group 4 will receive 4 vaccinations of either the DNA vaccine EP-HIV-1090 or placebo. Vaccinations will occur at Months 0, 1, 3, and 6.

In Part B, Group 5 will receive 4 vaccinations of either the protein vaccine EP-1043 plus DNA vaccine EP-HIV- 1090 or placebo. Vaccinations will occur at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.

Outcomes

Primary Outcome Measures

Safety as assessed by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences

Secondary Outcome Measures

Immunogenicity as assessed by HIV-specific cellular responses assessed by interferon-gamma ELISpot assays and intracellular cytokine staining
Social impacts as assessed by negative experiences or problems reported by the participants

Full Information

First Posted
August 30, 2005
Last Updated
October 13, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00141024
Brief Title
Safety of and Immune Response to the Experimental Preventive HIV Vaccine, EP HIV-1090, in Healthy, HIV-1 Uninfected Adults
Official Title
A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of the Recombinant Protein Vaccine EP-1043 and the DNA Vaccine EP HIV-1090 Given Alone or in Combination in Healthy, HIV-1-Uninfected Adult Participants
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
The purpose of the study is to determine the safety of and immune response to the investigational HIV vaccine, EP HIV-1090, in HIV uninfected adults.
Detailed Description
The worldwide HIV/AIDS epidemic may only be controlled through the development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. EP HIV-1090 is a DNA HIV CTL vaccine; the proteins for which its genes code are designed to interact with CD8 cells (CTL) and cause CD8 cell proliferation. The DNA plasmids in EP HIV-1090 code for proteins conserved among HIV subtypes A, B, C, D, F, and G, which encompass the HLA subtypes of 85% of the worldwide general population. Participants will be enrolled in this study for 1 year. Group 4 participants will receive EP HIV-1090 or placebo at study entry and Months 1, 3, and 6. There will be 11 study visits that will occur at screening; study entry; and Months 0.5, 1, 1.5, 3, 3.5, 6, 6.5, 9, and 12. A physical exam and risk reduction/pregnancy prevention counseling will occur at each visit. Participants will be asked about their adverse experiences from vaccination at each visit. Blood and urine collection will occur at selected visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV Seronegativity, HIV Preventive Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Group 1 will receive 4 vaccinations of the EP-1043 vaccine or placebo. Vaccinations will be given at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.
Arm Title
2
Arm Type
Experimental
Arm Description
Group 2 will receive 4 vaccinations of the EP-1043 vaccine or placebo. Vaccinations will be given at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.
Arm Title
3
Arm Type
Experimental
Arm Description
In Part B, Group 3 will receive 4 vaccinations of either the EP-1043 vaccine or placebo. Vaccinations will occur at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.
Arm Title
4
Arm Type
Experimental
Arm Description
In Part B, Group 4 will receive 4 vaccinations of either the DNA vaccine EP-HIV-1090 or placebo. Vaccinations will occur at Months 0, 1, 3, and 6.
Arm Title
5
Arm Type
Experimental
Arm Description
In Part B, Group 5 will receive 4 vaccinations of either the protein vaccine EP-1043 plus DNA vaccine EP-HIV- 1090 or placebo. Vaccinations will occur at Months 0, 1, 3, and 6. This group was discontinued as of 12/26/06.
Intervention Type
Biological
Intervention Name(s)
EP HIV-1043
Intervention Description
Recombinant protein vaccine containing the 18 HIV proteins from HIV genes Pol, Vpu, and Gag. The vaccine is provided in single-use 1.1-mL vials.
Intervention Type
Biological
Intervention Name(s)
EP HIV-1090
Intervention Description
DNA plasmid vaccine containing the genes Gag, Pol, Vpr, Nef, Rev, and Env. The vaccine is provided in single-use 1.1-mL vials.
Primary Outcome Measure Information:
Title
Safety as assessed by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences
Time Frame
After each injection and for 12 months following the first injection
Secondary Outcome Measure Information:
Title
Immunogenicity as assessed by HIV-specific cellular responses assessed by interferon-gamma ELISpot assays and intracellular cytokine staining
Time Frame
Throughout the study
Title
Social impacts as assessed by negative experiences or problems reported by the participants
Time Frame
Throughout the study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Note: Groups 1, 2, 3, and 5 have permanently discontinued enrollment per the 12/26/06 letter of amendment. Inclusion Criteria: Good general health Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed for the duration of the study Willing to receive HIV test results Have understanding of the study Willing to use acceptable forms of contraception Negative pregnancy test Exclusion Criteria: HIV vaccines in a 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 prophylaxis or therapy 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 Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded. Autoimmune disease or immunodeficiency Active syphilis infection unless the participant has completed full treatment for syphilis 6 months prior to enrollment Unstable asthma Diabetes mellitus type 1 or 2 Thyroid disease or thyroidectomy requiring treatment Serious angioedema within 3 years prior to enrollment Uncontrolled hypertension Body mass index (BMI) of 40 or greater BMI of 35 or greater if the participant is older than 45 years, has systolic blood pressure greater than 140 mm Hg, has diastolic blood pressure greater than 90 mm Hg, smokes, or has known hyperlipidemia Bleeding disorder Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period Seizure disorder requiring medication within the 3 years prior to enrollment Absence of the spleen Mental illness that would interfere with the study Other conditions that, in the judgment of the investigator, would interfere with the study Pregnancy, breastfeeding, or plans to become pregnant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xia Jin, MD, PhD
Organizational Affiliation
University of Rochester
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jorge Sanchez, MD
Organizational Affiliation
Asociación Civil Impacta Salud y Educación (IMPACTA)
Official's Role
Study Chair
Facility Information:
Facility Name
San Francisco Vaccine and Prevention CRS
City
San Francisco
State/Province
California
ZIP/Postal Code
94102-6033
Country
United States
Facility Name
Project Brave HIV Vaccine CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Univ. of Rochester HVTN CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642-0001
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12699356
Citation
Esparza J, Osmanov S. HIV vaccines: a global perspective. Curr Mol Med. 2003 May;3(3):183-93. doi: 10.2174/1566524033479825.
Results Reference
background
PubMed Identifier
12089434
Citation
Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D, Novitsky V, Haynes B, Hahn BH, Bhattacharya T, Korber B. Diversity considerations in HIV-1 vaccine selection. Science. 2002 Jun 28;296(5577):2354-60. doi: 10.1126/science.1070441.
Results Reference
background
PubMed Identifier
11535313
Citation
Livingston BD, Newman M, Crimi C, McKinney D, Chesnut R, Sette A. Optimization of epitope processing enhances immunogenicity of multiepitope DNA vaccines. Vaccine. 2001 Sep 14;19(32):4652-60. doi: 10.1016/s0264-410x(01)00233-x.
Results Reference
background
PubMed Identifier
15265928
Citation
McKinney DM, Skvoretz R, Livingston BD, Wilson CC, Anders M, Chesnut RW, Sette A, Essex M, Novitsky V, Newman MJ. Recognition of variant HIV-1 epitopes from diverse viral subtypes by vaccine-induced CTL. J Immunol. 2004 Aug 1;173(3):1941-50. doi: 10.4049/jimmunol.173.3.1941.
Results Reference
background
PubMed Identifier
14607970
Citation
Wilson CC, McKinney D, Anders M, MaWhinney S, Forster J, Crimi C, Southwood S, Sette A, Chesnut R, Newman MJ, Livingston BD. Development of a DNA vaccine designed to induce cytotoxic T lymphocyte responses to multiple conserved epitopes in HIV-1. J Immunol. 2003 Nov 15;171(10):5611-23. doi: 10.4049/jimmunol.171.10.5611.
Results Reference
background
PubMed Identifier
25820067
Citation
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.
Results Reference
derived

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Safety of and Immune Response to the Experimental Preventive HIV Vaccine, EP HIV-1090, in Healthy, HIV-1 Uninfected Adults

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