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

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ClinicalTrials.gov Identifier: NCT00272493

Recruitment Status : Completed

First Posted : January 6, 2006

Last Update Posted : May 28, 2012

Sponsor:

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
HIV Infections	Biological: Hepatitis B virus vaccine with GM-CSF adjuvant Biological: Hepatitis B virus vaccine	Phase 2

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	48 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Actual Primary Completion Date :	November 2007
Actual Study Completion Date :	September 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis B

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

Quantitative hepatitis B surface antibody (HBsAb) [ Time Frame: At Week 16 ]
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 ]

Secondary Outcome Measures :

Quantitative HBsAb 24 and 48 weeks after completion of HBV vaccination series [ Time Frame: 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 [ Time Frame: At Weeks 16, 36, and 60 ]
Changes in HIV viral load from baseline [ Time Frame: At Weeks 4, 16, and 60 ]
Changes in white blood cell and absolute neutrophil count from baseline [ Time Frame: At Weeks 4, 16, and 36 ]
Occurrence of Grade 2 or higher adverse events [ Time Frame: Throughout the study ]
Changes in CD4 count from baseline [ Time Frame: At Weeks 4, 16, and 60 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

National Institute of Allergy and Infectious Diseases (NIAID)

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

Publications of Results:

Overton ET, Kang M, Peters MG, Umbleja T, Alston-Smith BL, Bastow B, Demarco-Shaw D, Koziel MJ, Mong-Kryspin L, Sprenger HL, Yu JY, Aberg JA. Immune response to hepatitis B vaccine in HIV-infected subjects using granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant: ACTG study 5220. Vaccine. 2010 Aug 2;28(34):5597-604. doi: 10.1016/j.vaccine.2010.06.030. Epub 2010 Jun 23.

Other Publications:

Bica I, McGovern B, Dhar R, Stone D, McGowan K, Scheib R, Snydman DR. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis. 2001 Feb 1;32(3):492-7. Epub 2001 Jan 23.

Laurence JC. Hepatitis A and B immunizations of individuals infected with human immunodeficiency virus. Am J Med. 2005 Oct;118 Suppl 10A:75S-83S. Review.

Sasaki Md, Foccacia R, de Messias-Reason IJ. Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection. Vaccine. 2003 Nov 7;21(31):4545-9.

Thio CL, Seaberg EC, Skolasky R Jr, Phair J, Visscher B, Muñoz A, Thomas DL; Multicenter AIDS Cohort Study. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002 Dec 14;360(9349):1921-6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Anthony DD, Umbleja T, Aberg JA, Kang M, Medvik K, Lederman MM, Peters MG, Koziel MJ, Overton ET. Lower peripheral blood CD14+ monocyte frequency and higher CD34+ progenitor cell frequency are associated with HBV vaccine induced response in HIV infected individuals. Vaccine. 2011 Apr 27;29(19):3558-63. doi: 10.1016/j.vaccine.2011.02.092. Epub 2011 Mar 11.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00272493 History of Changes
Other Study ID Numbers:	A5220 10148 ( Registry Identifier: DAIDS ES Registry ID ) ACTG A5220
First Posted:	January 6, 2006 Key Record Dates
Last Update Posted:	May 28, 2012
Last Verified:	May 2012

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


Treatment Experienced Treatment Naive

Additional relevant MeSH terms:


HIV Infections Hepatitis B Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases	Hepadnaviridae Infections DNA Virus Infections Hepatitis, Viral, Human Hepatitis Liver Diseases Digestive System Diseases Vaccines Immunologic Factors Physiological Effects of Drugs

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