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

HIV Infections Clinical Trial

Official title:

Immunologic Effects of CpG ODN Administration to HIV Uninfected and HIV Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00100633
• Other study ID #: PO1AI55793
• Secondary ID: PO1-AI-55793
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 4, 2005
• Last updated: September 29, 2008
• Start date: December 2004
• Est. completion date: October 2007

Study information

• Verified date: December 2007
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• HIV Infections

Intervention

Drug:
• CpG7909 oligodeoxynucleotides (ODN)

Biological:
• Hepatitis B virus vaccine

Locations

Country	Name	City	State
United States	University Hospitals of Cleveland	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

Schlaepfer E, Audigé 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of HIV peptides to which HIV infected patients respond using ELISPOT (CpG vs. no CpG in HIV infected participants)
Primary	total number of CD8+ lymphocytes responding after HIV-peptide stimulation using ELISPOT (CpG vs. no CpG in HIV infected participants)
Primary	safety
Secondary	Percentage of patients who develop protective hepatitis B (HB) antibody concentration (CpG vs. no CpG in HIV infected participants)
Secondary	percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in HIV infected participants)
Secondary	percentage of patients who develop HB specific CD8+ lymphocyte responses using ELISPOT (CpG vs. no CpG in all participants)
Secondary	percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in HIV infected participants)
Secondary	percentage of patients who develop CD8+ lymphocyte proliferative responses as measured using CFSE (CpG vs. no CpG in all participants)
Secondary	expression of costimulatory molecules on B-cells in peripheral blood (CpG vs. no CpG in HIV infected participants)
Secondary	expression of costimulatory molecules on B-cells in peripheral blood (CpG recipients, HIV infected vs. uninfected participants)
Secondary	spontaneous IFN-gamma production in peripheral blood (CpG recipients, HIV infected vs. uninfected participants)

External Links

•   Click here for more information on the Cleveland AIDS Clinical Trials Unit