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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00272493
• Other study ID #: A5220
• Secondary ID: 10148ACTG A5220
• Status: Completed
• Phase: Phase 2
• Est. completion date: September 2008

Study information

• Verified date: May 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: September 2008
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis B
• HIV Infections

Intervention

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

Locations

Country	Name	City	State
United States	Northwestern University CRS	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	Case CRS	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State Univ. AIDS CRS	Columbus	Ohio
United States	Univ. of Rochester ACTG CRS	Durham	North Carolina
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	Washington U CRS	Saint Louis	Missouri
United States	University of Washington AIDS CRS	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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 f — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantitative hepatitis B surface antibody (HBsAb)		At Week 16
Primary	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)		Throughout the study
Secondary	Quantitative HBsAb 24 and 48 weeks after completion of HBV vaccination series		At Weeks 36 and 60
Secondary	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
Secondary	Changes in HIV viral load from baseline		At Weeks 4, 16, and 60
Secondary	Changes in white blood cell and absolute neutrophil count from baseline		At Weeks 4, 16, and 36
Secondary	Occurrence of Grade 2 or higher adverse events		Throughout the study
Secondary	Changes in CD4 count from baseline		At Weeks 4, 16, and 60

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