A Phase I/II Randomised Therapeutic HIV Vaccine Trial in Individuals Who Started Antiretrovirals During Primary or Chronic Infection
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Efficacy: Time from treatment interruption to the earliest of reaching HIV RNA ≥ 10,000 copies/ml or resuming antiretroviral therapy for any reason over a period of 24 weeks.
研究概览
简要总结
EVHA T01 is an international, phase I/II, multicentre, multi-stage, double-blind study that will evaluate at least three experimental arms compared to placebo control in HIV-1 infected participants to see if one or more has a clinically relevant impact on the control of viral replication.
详细描述
The randomization ratio is 1:1:1:1 for vaccine: vedolizumab: combination: placebo in one of 3 schedules.
The study contains a phase I component in order to evaluate the local and systemic reactogenicity following the first administration of products in the first 12 participants. The phase I will consist of a slow enrolment of the first 12 participants who will be randomised at a maximum rate of 1 per week for 4 weeks, then 2 per week for 4 weeks before increasing to 4 or more per week. The IDMC will review of cumulative adverse event data through to and including the first safety visit in the 12th participant and their recommendation will be sought with regard to expanding recruitment.
The phase II component will assess the effectiveness and safety of the three experimental strategies upon viral control following analytic treatment interruption (ATI). The phase II component is divided into two stages, an interim efficacy stage and a final efficacy stage. There will be a pause in enrolment after 88 participants have been enrolled. A planned interim review by the IDMC at the end of the first stage will provide an opportunity to modify the design of subsequent stages or the recruitment strategy.
Screening will take place during the 6 weeks prior to randomisation. Eligible participants will be enrolled at week 0 and randomised to vaccine, vedolizumab, the combination of vaccine and vedolizumab or matched placebos. Participants and study staff will be aware of the schedule the participant is randomised to, with a third allocated to injections, a third to infusions and a third to the combination of injections and infusions. Only staff authorised to prepare the products will know who is randomised to active product or placebo within each schedule in a ratio of 3:1 respectively.
The vaccine regimen will start at week 0 and the vedolizumab regimen at week 2, each with matched placebo.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Injection only: Active:placebo (3:1)
GTU-MultiHIV B-clade + MVA HIV-B:
GTU-MultiHIV B-clade - 2 mg of DNA in 1ml encoding a multi HIV antigen (synthetic fusion protein) administered intramuscularly into the non-dominant deltoid muscle at weeks 0 and 4 and MVA HIV-B 0.5ml(1 x108 pfu/ml) MVA encoding the full-length codon-optimized sequence of Gag administered intramuscularly into the non-dominant deltoid muscle at week 12.
干预措施: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine (Biological)
Placebo
Placebo1 for DNA: Sodium chloride for injection, 0.9% in 1ml administered intramuscularly into the non-dominant deltoid muscle at weeks 0 and 4.
Placebo 2 for MVA: S08 buffer in 0.5ml administered intramuscularly into the non-dominant deltoid muscle at week 12.
Placebo for mAb: Sodium Chloride (NaCl) for infusion, 0.9% in 250 ml infusion bags.
干预措施: Placebo (Other)
Injection only: Active:placebo (3:1)
GTU-MultiHIV B-clade + MVA HIV-B:
GTU-MultiHIV B-clade - 2 mg of DNA in 1ml encoding a multi HIV antigen (synthetic fusion protein) administered intramuscularly into the non-dominant deltoid muscle at weeks 0 and 4 and MVA HIV-B 0.5ml(1 x108 pfu/ml) MVA encoding the full-length codon-optimized sequence of Gag administered intramuscularly into the non-dominant deltoid muscle at week 12.
干预措施: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine+ Vedolizumab (Biological)
Infusion only: Active:placebo (3:1)
Vedolizumab will be administered in the participant's dominant arm as an intravenous infusion over 30 mins.
干预措施: Vedolizumab 300 MG [Entyvio] (Drug)
Injection and Infusion: Active:placebo (3:1)
GTU-MultiHIV B-clade + MVA HIV-B + Vedolizumab
干预措施: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine (Biological)
Injection and Infusion: Active:placebo (3:1)
GTU-MultiHIV B-clade + MVA HIV-B + Vedolizumab
干预措施: GTU-MultiHIV B-clade vaccine + MVA HIV-B HIV vaccine+ Vedolizumab (Biological)
Injection and Infusion: Active:placebo (3:1)
GTU-MultiHIV B-clade + MVA HIV-B + Vedolizumab
干预措施: Vedolizumab 300 MG [Entyvio] (Drug)
结局指标
主要结局
Efficacy: Time from treatment interruption to the earliest of reaching HIV RNA ≥ 10,000 copies/ml or resuming antiretroviral therapy for any reason over a period of 24 weeks.
时间窗: Time from treatment interruption (scheduled for 12 weeks after completing the immunisation schedule) to the earliest of reaching HIV RNA ≥ 10,000 copies/ml or resuming antiretroviral therapy for any reason over a period of 24 weeks.
Safety: A clinical decision to discontinue the regimen for an adverse event that is considered related to product
时间窗: From randomisation
次要结局
- Grade 3 and worse solicited clinical and laboratory adverse events(From randomisation to study completion, about 60 weeks.)
- Any event leading to interruption in the vaccine schedule(From randomisation to study completion, about 60 weeks.)
- Any event that results in resuming treatment during the ATI(From randomisation to study completion, about 60 weeks.)
- Serious Adverse Events(From randomisation to 30 days after the last protocol visit)
- Other clinical and laboratory adverse events(From randomisation to study completion, about 60 weeks.)
- Time to VL suppression after restarting ART(From randomisation to VL suppression after restarting ART)