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

October 15, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611-3015
        • Northwestern University CRS
      • Chicago, Illinois, United States, 60611
        • Rush Univ. Med. Ctr. ACTG CRS
    • Missouri
      • Saint Louis, Missouri, United States, 63108-2138
        • Washington U CRS
    • New York
      • New York, New York, United States, 10016-6481
        • NY Univ. HIV/AIDS CRS
      • Rochester, New York, United States, 14642-0001
        • Univ. of Rochester ACTG CRS
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Univ. of Rochester ACTG CRS
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0405
        • Univ. of Cincinnati CRS
      • Cleveland, Ohio, United States, 44106-5083
        • Case CRS
      • Cleveland, Ohio, United States, 44109-1998
        • MetroHealth CRS
      • Columbus, Ohio, United States, 43210
        • The Ohio State Univ. AIDS CRS
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington AIDS CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Quantitative hepatitis B surface antibody (HBsAb)
Time Frame: At Week 16
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
Throughout the study

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Edgar (Turner) Overton, MD, AIDS Clinical Trials Unit, Washington University at St. Louis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

January 4, 2006

First Submitted That Met QC Criteria

January 4, 2006

First Posted (Estimate)

January 6, 2006

Study Record Updates

Last Update Posted (Actual)

October 25, 2021

Last Update Submitted That Met QC Criteria

October 15, 2021

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5220
  • 10148 (Registry Identifier: DAIDS ES Registry ID)
  • ACTG A5220

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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