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

Study Overview
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Hepatitis B virus vaccine with GM-CSF adjuvant
* Biological: Hepatitis B virus vaccine


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12. | Biological: Hepatitis B virus vaccine<br>* Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.<br>|
| Experimental: B<br>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<br>* Arm B participants will receive 40 mcg of HBV vaccine and 250 mcg of GM-CSF at study entry, Week 4, and Week 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Changes in CD4 count from baseline |  | At Weeks 4, 16, and 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Experienced, Treatment Naive