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

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00272493

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 II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: AIDS Hepatitis Hepatitis B

Drug Information available for: Granulocyte-macrophage colony-stimulating factor Sargramostim Hepatitis B Vaccines

U.S. FDA Resources

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 Start Date:	December 2006
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator 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.
B: Experimental 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

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

Locations

United States, Illinois
Feinberg School of Medicine
Chicago, Illinois, United States, 60611-3015
Rush. Univ. Med. Ctr, Dept of Infectious Disease
Chicago, Illinois, United States, 60611
United States, Maryland
University of Maryland Biotech. Institute, Inst. of Human Virology
Baltimore, Maryland, United States, 21201
United States, Missouri
Washington University (St. Louis)
St. Louis, Missouri, United States, 63108-2138
United States, New York
NYU/Bellevue
New York, New York, United States, 10016-6481
Univ. of Rochester Med. Ctr.
Rochester, New York, United States, 14642-0001
AIDS Community Health Ctr.
Rochester, New York, United States, 14642-0001
United States, North Carolina
Duke University Medical Center Division of Infectious Diseases
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western Reserve Univ.
Cleveland, Ohio, United States, 44106-5083
MetroHealth Med. Ctr.
Cleveland, Ohio, United States, 44109-1998
Univ. of Cincinnati
Cincinnati, Ohio, United States, 45267-0405
Ohio State Univ. College of Medicine
Columbus, Ohio, United States, 43210
United States, Texas
Univ. of Texas Medical Branch, ACTU
Galveston, Texas, United States, 77555-0435
United States, Washington
University of Washington, Harbor Medical Center
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

Additional Information:

Haga clic aquí para ver información sobre este ensayo clínico en español This link exits the ClinicalTrials.gov site

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 MG, 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, Munoz 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.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5220
Study First Received:	January 4, 2006
Last Updated:	July 31, 2009
ClinicalTrials.gov Identifier:	NCT00272493 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Treatment Experienced
Treatment Naive

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
Liver Diseases
Immunologic Factors
Acquired Immunodeficiency Syndrome
Adjuvants, Immunologic
Hepatitis, Viral, Human
Immunologic Deficiency Syndromes
Hepatitis

Virus Diseases
Digestive System Diseases
HIV Seropositivity
HIV Infections
Sexually Transmitted Diseases
Hepatitis B
DNA Virus Infections
Retroviridae Infections

Additional relevant MeSH terms:

Liver Diseases
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Acquired Immunodeficiency Syndrome
Adjuvants, Immunologic
Hepatitis, Viral, Human
Infection
Hepadnaviridae Infections

Pharmacologic Actions
Immunologic Deficiency Syndromes
Hepatitis
Virus Diseases
Digestive System Diseases
HIV Infections
Sexually Transmitted Diseases
Hepatitis B
Lentivirus Infections
DNA Virus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on September 01, 2009