Safety and Effectiveness of an Adjuvant in Improving Immune Response to Hepatitis B Virus Vaccine in HIV Infected Individuals

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00272493
First received: January 4, 2006
Last updated: May 17, 2012
Last verified: May 2012

January 4, 2006
May 17, 2012
Not Provided
November 2007   (final data collection date for primary outcome measure)
  • Quantitative hepatitis B surface antibody (HBsAb) [ Time Frame: At Week 16 ] [ Designated as safety issue: No ]
  • Occurrence of Grade 3 or higher adverse events (including hypersensitivity reaction) related to study regimens and HIV viral load increase greater than 1 log(10) [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
  • Quantitative hepatitis B surface antibody (HBsAb) 4 weeks after completion of HBV vaccination series, at Week 16
  • occurrence of Grade 3 or higher adverse events (including hypersensitivity reaction) related to study regimens
Complete list of historical versions of study NCT00272493 on ClinicalTrials.gov Archive Site
  • Quantitative HBsAb 24 and 48 weeks after completion of HBV vaccination series [ Time Frame: At Weeks 36 and 60 ] [ Designated as safety issue: No ]
  • HBsAb response, defined as titer greater than 10 mlU/ml at 4, 24, and 48 weeks after completion of HBV vaccination series [ Time Frame: At Weeks 16, 36, and 60 ] [ Designated as safety issue: No ]
  • Changes in HIV viral load from baseline [ Time Frame: At Weeks 4, 16, and 60 ] [ Designated as safety issue: No ]
  • Changes in white blood cell and absolute neutrophil count from baseline [ Time Frame: At Weeks 4, 16, and 36 ] [ Designated as safety issue: No ]
  • Occurrence of Grade 2 or higher adverse events [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
  • Changes in CD4 count from baseline [ Time Frame: At Weeks 4, 16, and 60 ] [ Designated as safety issue: No ]
  • Quantitative HBsAb 24 and 48 weeks after completion of HBV vaccination series, at Weeks 36 and 60
  • HBsAb response, defined as titer greater than 10 mlU/ml at 4, 24, and 48 weeks after completion of HBV vaccination series, at Weeks 16, 36, and 60
  • changes in HIV viral load from baseline at Weeks 4, 16, and 60
  • changes in white blood cell and absolute neutrophil count from baseline at Weeks 4, 16, and 36, and changes in CD4 count from baseline at Weeks 4, 16, and 60
  • occurrence of Grade 2 or higher adverse events
Not Provided
Not Provided
 
Safety and Effectiveness of an Adjuvant in Improving Immune Response to Hepatitis B Virus Vaccine in HIV Infected Individuals
Improving Immune Response to Hepatitis B Vaccine in HIV-positive Subjects Using Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) as a Vaccine Adjuvant: A Phase II Open-Label Pilot Study

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a naturally occurring substance that is made by the body in response to infection or inflammation, and greatly improves cellular immune responses. The purpose of this study is to evaluate the safety and effectiveness of GM-CSF as an adjuvant to improve the immune response to hepatitis B virus (HBV) vaccination in HIV infected individuals.

Highly active antiretroviral therapy (HAART) has greatly improved the life of HIV infected individuals. Before the introduction of HAART, the impact of HBV infection and liver disease was less prominent due to the rapid progression to AIDS. However, with the use of HAART, liver disease has become a leading cause of death in HIV infected individuals; therefore, prevention of HBV infection is essential. Most HIV infected people respond poorly to HBV vaccines. GM-CSF is a cytokine produced primarily by activated T and B cells and has been used extensively as a hematopoietic growth factor. GM-CSF increases neutrophil count, improves antigen-presenting cell function, and is involved in the development and improvement of cellular immune responses. Past research has shown that GM-CSF improves the immune response to HBV vaccination in people with kidney disease. The purpose of this study is to evaluate the safety and effectiveness of GM-CSF as an adjuvant to improve the immune response to HBV vaccination in HIV infected individuals.

This study will last 60 weeks. Participants will be randomly assigned to 1 of 2 arms. Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12. Arm B participants will receive 40 mcg of HBV vaccine and 250 mcg of GM-CSF at study entry, Week 4, and Week 12. Participants will be stratified by their screening HIV-1 viral load. After completing the vaccination series, study visits will occur at Weeks 16, 36, and 60. Blood collection, a physical exam, and liver function and hepatitis antibody tests will be completed at all study visits. Telephone follow-up by study staff will occur 48 to 96 hours post-vaccination.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
HIV Infections
  • Biological: Hepatitis B virus vaccine with GM-CSF adjuvant
    Arm B participants will receive 40 mcg of HBV vaccine and 250 mcg of GM-CSF at study entry, Week 4, and Week 12.
  • Biological: Hepatitis B virus vaccine
    Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.
  • Active Comparator: A
    Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.
    Intervention: Biological: Hepatitis B virus vaccine
  • Experimental: B
    Arm B participants will receive 40 mcg of HBV vaccine and 250 mcg of GM-CSF at study entry, Week 4, and Week 12.
    Intervention: Biological: Hepatitis B virus vaccine with GM-CSF adjuvant

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
September 2008
November 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV infected
  • CD4 count of 200 cells/mm3 or more within 30 days prior to study entry
  • HIV-1 RNA viral load value obtained within 30 days prior to study entry
  • Received HAART for at least 8 weeks prior to study entry OR not on HAART within 8 weeks prior to study entry with no plans to start HAART during the study. Participants receiving HAART must be on stable therapy as defined by the protocol.
  • Negative hepatitis B core total antibody (HBcAb total), qualitative hepatitis B surface antibody (HBsAb), and hepatitis B surface antigen (HBsAg) tests within 30 days prior to study entry
  • Negative hepatitis C virus (HCV) antibody test, completed within 30 days prior to study entry
  • Willing to use acceptable forms of contraception

Exclusion Criteria:

  • HCV antibody or HCV RNA positive at any time prior to study entry
  • Previously vaccinated against HBV
  • Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, vaccines, interleukins, interferons, growth factors, or intravenous immune globulin within 30 days prior to study entry
  • Known allergy or sensitivity to any component of the study drugs
  • Active drug or alcohol dependence that would interfere with participation in the study
  • Any mental illness that may interfere with the study
  • Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.
  • Body weight less than 50 kg (110 lbs)
  • Abnormal lab values
  • Pregnant or breastfeeding
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00272493
A5220, 10148, ACTG A5220
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: Judith A. Aberg, MD New York University
Study Chair: Edgar (Turner) Overton, MD AIDS Clinical Trials Unit, Washington University at St. Louis
National Institute of Allergy and Infectious Diseases (NIAID)
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP