Maraviroc Immune Recovery Study, A Multicenter, Randomized, Placebo-controlled, Exploratory Mechanistic Study Into the Role of Maraviroc on Immune Recovery
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 85
- 试验地点
- 10
- 主要终点
- 30% increase in CD4+ cell count after 48 weeks
研究概览
简要总结
Rationale: Improving cellular immunity by means of increasing CD4 cells is one of the goals of antiretroviral therapy in HIV, which is achieved by means of virological suppression. A certain group of patients, the so called "immunologic non responders", fail to reach an acceptable CD4 cell increase despite an adequate virologic response on antiretroviral treatment. Recently a new antiretroviral agent, maraviroc (Celsentry®), is registered for the treatment of patients infected with CCR5 tropic HIV-1 virus. However, data is available suggesting that treatment with maraviroc leads to immune recovery (increase in CD4 cells) in patients who are infected with dual/mixed tropic HIV-1 virus, in the absence of a virologic response. This suggests an alternative mechanism for immune recovery, which could be especially beneficial for this group of patients.
Hypothesis: Maraviroc, by a yet unknown mechanism, stimulates immune recovery by increasing CD4+ cell count.
Objective: The primary objective is to confirm the hypothesis that maraviroc stimulates immune recovery; the secondary objective is to explore, by virologic and immunologic investigations, the underlying mechanisms of this hypothesis.
Study design: multicentre, randomized, placebo-controlled, double blind, exploratory mechanistic study.
Study population: HIV-1 infected patients 18 years or older, who meet the inclusion criteria.
Intervention: One group receives maraviroc (dose dependent on co-medication), the other group placebo.
Main study parameters/endpoints: A 30% increase in CD4 cell rise in the treatment group (compared with placebo).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
- In the treatment group subjects will start with a registered antiretroviral agent (maraviroc).
- During the treatment year patients will perform several study visits, probably three more compared with regular visits on the outpatient clinic.
- Each visit, blood will be drawn by venepuncture for immunologic and virologic investigations (see flow chart).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age 18 years or older
- •HAART with a maximal treatment interruption of two weeks
- •viral suppression (< 50 copies/ml) for 6 months
- •And either:
- •CD4+ count < 200 cells/microliter after minimal one year of treatment with HAART (study group one) OR
- •a CD4+ cell count between 200 and 350 cells/microliter after minimal two years of treatment with HAART (study group two)
排除标准
- •HAART consisting of a combination of tenofovir and didanosine
- •Active infection for which antimicrobial treatment
- •Acute hepatitis B or C
- •Chronic hepatitis B or C for which treatment with (peg)interferon and/or ribavirin (Note: patients with untreated chronic hepatitis B or C can be included)
- •Immunosuppressive medication
- •Radiotherapy or chemotherapy in the past 2 years
- •Pregnancy or breastfeeding an infant
- •Subjects with known hypersensitivity to maraviroc or to peanuts, or any of its excipients or dyes as follows:
- •Excipients from tablet: microcrystalline cellulose, dibasic calcium phosphate (anhydrous), sodium starch glycolate, magnesium stearate.
- •Film-coat: [Opadry II Blue (85G20583) contains FD&C blue #2 aluminium lake, soya lecithin, polyethylene glycol (macrogol 3350), polyvinyl alcohol, talc and titanium dioxide.
研究组 & 干预措施
Maraviroc
干预措施: maraviroc (Drug)
Placebo
Placebo drug
干预措施: Placebo (Drug)
结局指标
主要结局
30% increase in CD4+ cell count after 48 weeks
时间窗: 48 weeks
次要结局
未报告次要终点
研究者
S.F.L. van Lelyveld
Coordinating investigator
UMC Utrecht