Phase 2 Study to Evaluate the Safety of and the Immunogenicity to an Adjuvanted A(H1N1)v Influenza Vaccine in HIV-Infected Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 450
- 试验地点
- 1
- 主要终点
- proportions of seroconversion
研究概览
简要总结
This is a randomized, open label, phase II trial to evaluate the safety and immunogenicity of two different schedules of vaccination against influenza A H1N1 in HIV-infected individuals, in which each of the randomized groups will be compared with HIV-negative volunteers vaccinated with the regimen indicated by the Brazilian National Immunization Program. Will be included in the study HIV-infected patients, stratified by CD4 count (< 200 cells/mm3 or > 200 cells/mm3) at the time of screening for the study, not receiving antiretroviral therapy treatment or receiving stable treatment for at least 8 weeks, with no plans to change over the next 6 months, eligible to receive vaccine against influenza A H1N1. The control group will be formed by HIV-negative individuals, confirmed by serology performed at screening, eligible to receive vaccine against influenza A H1N1. Patients infected with HIV will receive one of two possible vaccination regimens: 1) 3.75 µg in two applications 21 days apart, 2) 7.5 µg in two applications 21 days apart. The volunteers in the control group will receive a single application of 3.75 µg dose of the vaccine. The study's hypotheses are: 1) The vaccine against the H1N1 virus promotes antibody titers above the level specified for protection (seroconversion), being as safe and well tolerated in patients HIV-1 infected as in non HIV-infected volunteers; 2) The proportion of seroconversion for H1N1 virus vaccine at a dose of 3.75 µg in HIV-1-infected patients is similar to the proportion of seroconversion induced by the same vaccine at a dose of 7.5 µg; 3)The proportion of seroconversion with one dose of the vaccine against H1N1 virus is similar to the proportion after the second dose.
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 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for all participants
- •Both genders, aged between 18 and 59 years;
- •Capacity to give informed consent voluntarily to participate in the study;
- •Study participants with reproductive potential (defined as girls after menarche or women who have not reached menopause at least during 24 consecutive months, or who menstruated during the past 24 months, or have not undergone surgical sterilization) must have pregnancy test negative results, in blood or urine, at screening and in the vaccine application days. If they have sexual practices likely to promote pregnancy, the participants must use some form of contraception during the study period. At least one of the following methods MUST be properly used: Condoms (male or female, Hormonal contraceptive.
- •Laboratory results in the study screening: hemoglobin > 8.0 g/dL; Direct bilirubin < 2.5 x the upper limit of normal; Alanine aminotransferase, ALT (SGPT) and aspartate aminotransferase, AST (SGOT) < 3 x the upper limit of normal; Platelet count > 100.000/mm3
- •Inclusion Criteria - unique to the participants with HIV infection:
- •HIV-1 infection (as evidenced by rapid HIV testing or ELISA kit approved and confirmed by repeating the ELISA, IFA, Western blot, HIV-1 plasma viral load) at any time before entering the study.
- •Without changing the antiretroviral treatment within 8 weeks prior to the screening for the study: If the volunteer is receiving HAART he/she is required to be using the same regimen within at least 8 weeks before screening. Changes in antiretroviral dosage within 8 weeks prior to entering the study are permitted. In addition, the exchange of pharmacological formulation (eg. the conventional formulation for combination formulations) is allowed. If the volunteer is not on regular antiretroviral treatment, he/she should not have received any dose of any antiretroviral within 8 weeks prior to screening, including for the prevention of HIV vertical transmission (previous prophylactic and therapeutic regimens are allowed)
- •Without planning to change or start HAART in the next 6 months.
- •Inclusion criteria - unique to the participants without HIV infection (control group):
- •HIV-negative test result documented by rapid test approved in Brazil
- •Health professionals with indication of receiving H1N1 virus vaccine
排除标准
- •Use of any systemic anticancer or immunomodulator treatment, corticosteroid, experimental vaccines, interleukins, interferons, growth factors or intravenous immunoglobulin (IVIG) within 45 days prior to entry into the study.
- •Pregnancy or lactation.
- •Allergy and/or sensitivity or any known hypersensitivity to residues present in the vaccine (egg, chicken protein, egg albumin, formaldehyde, gentamicin sulphate and sodium deoxycholate) and/or thimerosal.
- •Use of alcohol or addiction or other conditions which in the opinion of the site's investigator, may interfere with compliance to the study requirements.
- •Serious illness requiring systemic treatment and/or hospitalization within 45 days prior to entry into the study
- •Severe febrile illness or acute infection at the time of screening for the study and/or days of vaccination
- •Vaccination against seasonal influenza in the last 12 months prior to study entry
- •Previous vaccination against influenza A H1N1
- •History or family history of Guillain-Barré Syndrome (parents, siblings, half-siblings or children).
- •Diagnosis of neurological condition including (but not limited to) the absence of deep tendon reflexes, Achilles and patellar, in both legs (four missing) in the last six months.
- •Disproportionate force loss in lower limb(s) compared to the upper limbs in the last six months.
研究组 & 干预措施
3.75 µg of the vaccine on days 0 and 21
Patients infected with HIV will receive 3.75 µg of an adjuvanted A H1N1 vaccine in two applications 21 days apart.
干预措施: Adjuvanted vaccine against H1N1 influenza virus (GSK) (Biological)
7.5 µg of the vaccine on days 0 and 21
Patients infected with HIV will receive 7.5µg of an adjuvanted A H1N1 vaccine in two applications 21 days apart.
干预措施: Adjuvanted vaccine against H1N1 influenza virus (GSK) (Biological)
3.75 µg of the vaccine on day 0
The volunteers in the control group will receive a single application of 3.75 µg dose of the vaccine.
干预措施: Adjuvanted vaccine against H1N1 influenza virus (GSK) (Biological)
结局指标
主要结局
proportions of seroconversion
时间窗: 21 days after vaccination regimen
proportions of seroconversion for influenza A H1N1 in each of the four subsets of HIV-positive patients, and in the control group
Safety of the A H1N1 vaccine at two different regimens in HIV-infected adults
时间窗: 1 months after vaccination
Safety and tolerability of the vaccine against H1N1 virus in different doses and administration regimens in IV-infected adults
proportions of seroprotection
时间窗: 21 days after vaccination regimen
proportions of seroprotection for influenza A H1N1 in each of the four subsets of HIV-positive patients and in the control group
次要结局
- Cellular immune responses to H1N1 vaccination in HIV-infected patients(12 months after vaccination)
- Changes in HIV viral load and CD4(12 months after vaccination)
- Prevalence of A H1N1 influenza symptomatic disease in the study population(12 months after vaccination)
- Persistence of antibodies against H1N1 virus(12 months after vaccination)
研究者
Marilia Santini de Oliveira
Medical doctor
Oswaldo Cruz Foundation