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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 11
- 主要终点
- Quantitative hepatitis B surface antibody (HBsAb)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Hepatitis B virus vaccine with GM-CSF adjuvant (Biological)
A
Arm A participants will receive 40 mcg of HBV vaccine at study entry, Week 4, and Week 12.
干预措施: Hepatitis B virus vaccine (Biological)
结局指标
主要结局
Quantitative hepatitis B surface antibody (HBsAb)
时间窗: 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)
时间窗: Throughout the study
次要结局
- Quantitative HBsAb 24 and 48 weeks after completion of HBV vaccination series(At Weeks 36 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 HIV viral load from baseline(At Weeks 4, 16, and 60)
- Changes in CD4 count from baseline(At Weeks 4, 16, 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)