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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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Biological: Hepatitis B virus vaccine with GM-CSF adjuvant
Biological: Hepatitis B virus vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 48
Study Completion Date: September 2008
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Arm A participants will receive 40 mcg of HBV vaccine 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.
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.
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00272493

Locations
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611-3015
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60611
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States, 63108-2138
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016-6481
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642-0001
United States, North Carolina
Univ. of Rochester ACTG CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267-0405
Case CRS
Cleveland, Ohio, United States, 44106-5083
MetroHealth CRS
Cleveland, Ohio, United States, 44109-1998
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 43210
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Judith A. Aberg, MD New York University
Study Chair: Edgar (Turner) Overton, MD AIDS Clinical Trials Unit, Washington University at St. Louis
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00272493     History of Changes
Other Study ID Numbers: A5220, 10148, ACTG A5220
Study First Received: January 4, 2006
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis B
DNA Virus Infections
Digestive System Diseases
Hepadnaviridae Infections
Hepatitis
Hepatitis, Viral, Human
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Liver Diseases
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014