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

NCT00272493 | Completed Phase 2

• 3 other identifiers: A522010148ACTG A5220
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 11

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.

Conditions

HIV Infections

Keywords

Treatment Experienced; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• Quantitative hepatitis B surface antibody (HBsAb)

  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)

  Throughout the study

Secondary Outcomes (6)

• Quantitative HBsAb 24 and 48 weeks after completion of HBV vaccination series

  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

  At Weeks 16, 36, and 60

• Changes in HIV viral load from baseline

  At Weeks 4, 16, and 60

• Changes in white blood cell and absolute neutrophil count from baseline

  At Weeks 4, 16, and 36

• Occurrence of Grade 2 or higher adverse events

  Throughout the study

Study Arms (2)

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

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

Interventions

Hepatitis B virus vaccine with GM-CSF adjuvant 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.

B

Hepatitis B virus vaccine BIOLOGICAL

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

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (11)

Northwestern University CRS

Chicago, Illinois, 60611-3015, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60611, United States

Location

Washington U CRS

St Louis, Missouri, 63108-2138, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016-6481, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642-0001, United States

Location

Univ. of Rochester ACTG CRS

Durham, North Carolina, 27710, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

Location

Case CRS

Cleveland, Ohio, 44106-5083, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109-1998, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Related Publications (6)

• 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.

  PMID: 11170959 BACKGROUND

• 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.

  PMID: 16271546 BACKGROUND

• 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.

  PMID: 14575766 BACKGROUND

• 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.

  PMID: 12493258 BACKGROUND

• 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.

  PMID: 20600512 RESULT

• 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.

  PMID: 21397720 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Hepatitis B Vaccines

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Judith A. Aberg, MD

  New York University

  STUDY CHAIR

• Edgar (Turner) Overton, MD

  AIDS Clinical Trials Unit, Washington University at St. Louis

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2006
• First Posted: January 6, 2006
• Primary Completion: November 1, 2007
• Study Completion: September 1, 2008
• Last Updated: October 25, 2021

Record last verified: 2012-05

Locations

US (11)