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

NCT ID: NCT00272493

Last Updated: 2021-10-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2008-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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A

Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.

Group Type ACTIVE_COMPARATOR

Hepatitis B virus vaccine

Intervention Type BIOLOGICAL

Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.

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.

Group Type EXPERIMENTAL

Hepatitis B virus vaccine with GM-CSF adjuvant

Intervention Type BIOLOGICAL

Arm B participants will receive 40 mcg of HBV vaccine and 250 mcg of GM-CSF at study entry, Week 4, and Week 12.

Interventions

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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.

Intervention Type BIOLOGICAL

Hepatitis B virus vaccine

Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Judith A. Aberg, MD

Role: STUDY_CHAIR

New York University

Edgar (Turner) Overton, MD

Role: STUDY_CHAIR

AIDS Clinical Trials Unit, Washington University at St. Louis

Locations

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Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Durham, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

MetroHealth CRS

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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. doi: 10.1086/318501. Epub 2001 Jan 23.

Reference Type BACKGROUND
PMID: 11170959 (View on PubMed)

Laurence JC. Hepatitis A and B immunizations of individuals infected with human immunodeficiency virus. Am J Med. 2005 Oct;118 Suppl 10A:75S-83S. doi: 10.1016/j.amjmed.2005.07.024.

Reference Type BACKGROUND
PMID: 16271546 (View on PubMed)

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. doi: 10.1016/s0264-410x(03)00500-0.

Reference Type BACKGROUND
PMID: 14575766 (View on PubMed)

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. doi: 10.1016/s0140-6736(02)11913-1.

Reference Type BACKGROUND
PMID: 12493258 (View on PubMed)

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.

Reference Type RESULT
PMID: 20600512 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21397720 (View on PubMed)

Other Identifiers

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10148

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5220

Identifier Type: -

Identifier Source: secondary_id

A5220

Identifier Type: -

Identifier Source: org_study_id