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Safety of and Immune Response to a Hepatitis B Virus Vaccine Given With a Booster (CpG7909 ODN) in HIV Infected and HIV Uninfected People

Primary Purpose

HIV Infections, Hepatitis B

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CpG7909 oligodeoxynucleotides (ODN)
Hepatitis B virus vaccine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Hepatitis B Vaccine, Treatment Experienced, Treatment Naive

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for HIV Infected Participants: HIV-1 infection If receiving combination antiretroviral therapy (ART), must have been on ART for at least 3 months prior to study entry. Patients who anticipate a change in treatment (either initiating ART or stopping ART) in the next 7 months are not eligible. CD4 count of 250 cells/mm3 or greater Negative HBsAb, HBsAg, and HBcAb Willing to use acceptable forms of contraception while on study treatment and for 24 weeks after study treatment has ended Inclusion Criteria for HIV Uninfected Participants: HIV uninfected Negative HBsAb, HBsAg, and HBcAb Willing to use acceptable forms of contraception while on study treatment and for 24 weeks after study treatment has ended Exclusion Criteria for All Participants: Cancer. Participants with squamous cell or basal cell skin cancer are not excluded. Autoimmune disease Immunosuppressive medications. People who use or have used corticosteroid nasal sprays are not excluded. People who have received fewer than 2 weeks of systemic corticosteroids with the last dose over a month prior to study entry are not excluded. Any medical or psychiatric condition or occupational responsibilities that may interfere with the study Immunomodulator or investigational agent therapy within 30 days prior to study entry Allergy/sensitivity to study drugs or their formulations, including thimerosal Current drug or alcohol use that, in the opinion of the investigator, would interfere with the study Active hepatitis C virus infection, as indicated by serum antibodies to HCV AND detectable HCV RNA in plasma Blood clotting abnormalities Any other condition that, in the opinion of the investigator, might interfere with the study Pregnancy or breastfeeding

Sites / Locations

  • University Hospitals of Cleveland

Outcomes

Primary Outcome Measures

Number of HIV peptides to which HIV infected patients respond using ELISPOT (CpG vs. no CpG in HIV infected participants)
total number of CD8+ lymphocytes responding after HIV-peptide stimulation using ELISPOT (CpG vs. no CpG in HIV infected participants)
safety

Secondary Outcome Measures

Percentage of patients who develop protective hepatitis B (HB) antibody concentration (CpG vs. no CpG in HIV infected participants)
percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in HIV infected participants)
percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in all participants)
percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in HIV infected participants)
percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in all participants)
expression of costimulatory molecules on B-cells in peripheral blood (CpG vs. no CpG in HIV infected participants)
expression of costimulatory molecules on B-cells in peripheral blood (CpG recipients, HIV infected vs. uninfected participants)
spontaneous IFN-gamma production in peripheral blood (CpG recipients, HIV infected vs. uninfected participants)

Full Information

First Posted
January 4, 2005
Last Updated
September 29, 2008
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00100633
Brief Title
Safety of and Immune Response to a Hepatitis B Virus Vaccine Given With a Booster (CpG7909 ODN) in HIV Infected and HIV Uninfected People
Official Title
Immunologic Effects of CpG ODN Administration to HIV Uninfected and HIV Infected Patients
Study Type
Interventional

2. Study Status

Record Verification Date
December 2007
Overall Recruitment Status
Completed
Study Start Date
December 2004 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
October 2007 (Actual)

3. Sponsor/Collaborators

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 a hepatitis B virus vaccine series given with a boosting agent, CpG7909 oligodeoxynucleotides (ODN), in HIV infected and HIV uninfected individuals who previously failed to develop a response to hepatitis B vaccine. Study hypothesis: Administration of CpG7909 ODN together with recombinant hepatitis B vaccine will result in increased frequency and magnitude of response to vaccine in individuals who have previously failed to mount a response to vaccination, and that in HIV infected subjects with detectable plasma viremia, it will lead to the enhancement of HIV-specific responses.
Detailed Description
As HIV disease progresses in HIV infected people, their immune responses to infectious and other foreign invaders becomes weaker; in particular, the cellular (T-cell) immune response is particularly affected by HIV. A boosting agent called CpG7909 ODN may be an ideal adjuvant for vaccines given to HIV infected people, because it may help elicit an increased CD8 T-cell response. This study will evaluate the safety of and immune response to a hepatitis B virus vaccine series given with CpG7909 ODN in HIV infected and uninfected people. There will be three groups in this study; participants will be stratified by baseline CD4 counts and viral load. Within each group, participants will be randomly assigned to receive 3 injections of hepatitis B vaccine with CpG7909 ODN or 3 injections of hepatitis B vaccine alone. Injections will be given at study entry and Months 1 and 6. There will be 10 study visits; a physical exam and blood collection will occur at each visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Hepatitis B
Keywords
Hepatitis B Vaccine, Treatment Experienced, Treatment Naive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
CpG7909 oligodeoxynucleotides (ODN)
Intervention Type
Biological
Intervention Name(s)
Hepatitis B virus vaccine
Primary Outcome Measure Information:
Title
Number of HIV peptides to which HIV infected patients respond using ELISPOT (CpG vs. no CpG in HIV infected participants)
Title
total number of CD8+ lymphocytes responding after HIV-peptide stimulation using ELISPOT (CpG vs. no CpG in HIV infected participants)
Title
safety
Secondary Outcome Measure Information:
Title
Percentage of patients who develop protective hepatitis B (HB) antibody concentration (CpG vs. no CpG in HIV infected participants)
Title
percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in HIV infected participants)
Title
percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in all participants)
Title
percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in HIV infected participants)
Title
percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in all participants)
Title
expression of costimulatory molecules on B-cells in peripheral blood (CpG vs. no CpG in HIV infected participants)
Title
expression of costimulatory molecules on B-cells in peripheral blood (CpG recipients, HIV infected vs. uninfected participants)
Title
spontaneous IFN-gamma production in peripheral blood (CpG recipients, HIV infected vs. uninfected participants)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for HIV Infected Participants: HIV-1 infection If receiving combination antiretroviral therapy (ART), must have been on ART for at least 3 months prior to study entry. Patients who anticipate a change in treatment (either initiating ART or stopping ART) in the next 7 months are not eligible. CD4 count of 250 cells/mm3 or greater Negative HBsAb, HBsAg, and HBcAb Willing to use acceptable forms of contraception while on study treatment and for 24 weeks after study treatment has ended Inclusion Criteria for HIV Uninfected Participants: HIV uninfected Negative HBsAb, HBsAg, and HBcAb Willing to use acceptable forms of contraception while on study treatment and for 24 weeks after study treatment has ended Exclusion Criteria for All Participants: Cancer. Participants with squamous cell or basal cell skin cancer are not excluded. Autoimmune disease Immunosuppressive medications. People who use or have used corticosteroid nasal sprays are not excluded. People who have received fewer than 2 weeks of systemic corticosteroids with the last dose over a month prior to study entry are not excluded. Any medical or psychiatric condition or occupational responsibilities that may interfere with the study Immunomodulator or investigational agent therapy within 30 days prior to study entry Allergy/sensitivity to study drugs or their formulations, including thimerosal Current drug or alcohol use that, in the opinion of the investigator, would interfere with the study Active hepatitis C virus infection, as indicated by serum antibodies to HCV AND detectable HCV RNA in plasma Blood clotting abnormalities Any other condition that, in the opinion of the investigator, might interfere with the study Pregnancy or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael M. Lederman, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15596832
Citation
Jiang JQ, Patrick A, Moss RB, Rosenthal KL. CD8+ T-cell-mediated cross-clade protection in the genital tract following intranasal immunization with inactivated human immunodeficiency virus antigen plus CpG oligodeoxynucleotides. J Virol. 2005 Jan;79(1):393-400. doi: 10.1128/JVI.79.1.393-400.2005.
Results Reference
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PubMed Identifier
15507621
Citation
Schlaepfer E, Audige A, von Beust B, Manolova V, Weber M, Joller H, Bachmann MF, Kundig TM, Speck RF. CpG oligodeoxynucleotides block human immunodeficiency virus type 1 replication in human lymphoid tissue infected ex vivo. J Virol. 2004 Nov;78(22):12344-54. doi: 10.1128/JVI.78.22.12344-12354.2004.
Results Reference
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Safety of and Immune Response to a Hepatitis B Virus Vaccine Given With a Booster (CpG7909 ODN) in HIV Infected and HIV Uninfected People

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