A Phase IIb Three-arm, Two-stage HIV Prophylactic Vaccine Trial With a Second Randomisation to Compare TAF/FTC to TDF/FTC as Pre-exposure Prophylaxis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,512
- 试验地点
- 1
- 主要终点
- Incident HIV infection
研究概览
简要总结
This international, multi-centre, double-blind vaccine study is a three-arm prospective 1:1:1 randomisation comparing each of two experimental combination vaccine regimens i.e. DNA/AIDSVAX (weeks 0,4,24,48) and DNA/CN54gp140 (weeks 0,4) + MVA/CN54gp140 (weeks 24,48) with placebo control. There will be a concurrent open-label 1:1 randomisation to compare daily TAF/FTC (week 0-26) to daily TDF/FTC (weeks 0-26) as pre-exposure prophylaxis.
The study aims to randomise up to 1668 eligible adults (18-40 years) through collaborating clinical research centres in 4 countries (Mozambique; South Africa; Tanzania; and Uganda). Each participant will be followed for a minimum of 74 weeks after enrolment.
The trial is designed to detect a reduction in HIV incidence that has public health relevance sufficient to justify implementation of the combination vaccine regimen. In light of the high level of effectiveness demonstrated in the PrEP trials (up to 86% reduction in HIV), this trial is powered to detect a protective vaccine efficacy of 70% at the final analysis.
The PrEP component will determine whether the effectiveness of TAF/FTC is unacceptably lower than the effectiveness of TDF/FTC.
详细描述
This international, multi-centre, double-blind vaccine study will be a three-arm prospective 1:1:1 randomisation comparing each of two experimental combination vaccine regimens with placebo control.
Pre-screening for risk and HIV status will take place as part of a Registration Cohort which will precede and continue in parallel to the PrEPVacc trial enrolments. This will give HIV negative volunteers time to learn about the PrEPVacc trial and facilitate timely enrolment.
Clinical screening for the vaccine trial will take place during the 8 weeks prior to randomisation from local communities in Mozambique, South Africa, Tanzania and Uganda where the clinical research centres are located. Eligible participants who are HIV-uninfected adults aged 18-40 years at high risk of HIV infection will be enrolled at week 0 and randomised to one of three vaccine arms:
- Vaccine group A: DNA-HIV-PT123 and AIDSVAX® B/E (weeks 0,4,24,48)
- Vaccine group B: DNA-HIV-PT123 and CN54gp140 in MPLA-L (wks 0,4), then MVA-CMDR and CN54gp140 in MPLA-L (wks 24,48)
- Vaccine group C: Saline Placebo (wks 0,4,24,48)
There will be a concurrent open-label 1:1 randomisation to one of two PrEP regimens:
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
- Triple (Care Provider, Investigator, Outcomes Assessor)
盲法说明
The vaccine component of PrEPVacc is placebo-controlled. Study staff, participants, laboratory staff and clinical staff assessing safety outcomes will not know who has been allocated vaccine or placebo, but pharmacy staff will know. The committee assessing the efficacy endpoints will not see the allocation in the first instance. The IDMC and statistical staff preparing the closed reports for the IDMC will also know the allocation.
Clinic staff will see the difference in volume between CN54gp140 in MPLA-L/matched placebo (0.4ml) and DNA-HIV-PT123/matched placebo (1ml) due to the position of the plunger, but they will not be able to differentiate between active and placebo.
The randomisation to control PrEP: experimental PrEP is 1:1 and all study staff and participants will know the allocation after randomisation as this is open-label.
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •HIV uninfected adults aged between 18 and 40 years old on the day of screening
- •Willing and able to provide informed consent prior to participation
- •Willing and able to comply with the visit schedule and provide blood, urine and other samples at the required time points
- •Home address accessible for visiting and intending to remain within the recruitment area for at least 82 weeks from screening
- •Likely to be at risk from exposure to HIV during follow up
- •Willing to undergo HIV testing, receive HIV test results and risk reduction counselling which includes promotion of PrEP and condoms
- •If female, of child-bearing age and not sterilised, willing to use a highly effective method of contraception from screening until 18 weeks after the last injection
- •If male and not sterilised, willing to avoid impregnating female partners from screening until 18 weeks after the last injection
排除标准
- •HIV infection or indeterminate HIV result at screening or enrolment
- •Hepatitis B surface antigen positive
- •If female, currently pregnant (evidence from positive serum or urine pregnancy test), or lactating
- •Participating in another biomedical research study or in receipt of a live vaccine within 30 days prior to randomisation
- •Participation in a previous HIV vaccine or HIV immunotherapy trial
- •Receiving blood products or immunoglobulins within 12 weeks of screening
- •Known hypersensitivity to any component of the vaccine formulations used in this trial or history of severe or multiple allergies to vaccines, drugs or pharmaceutical agents
- •Presence of a systemic disease at the time of randomisation or history of chronic illness that in the opinion of the investigator may compromise the participant's safety, preclude vaccination or compromise an immune response to vaccine
- •Abnormalities in routine laboratory parameters (Hb, creatinine, AST/ALT, alkaline phosphatase, total Bilirubin and glucose) of Grade 2 and above using the DAIDS toxicity table, version 2.1 July 2017 or estimated glomerular filtration rate less than 50ml/min
结局指标
主要结局
Incident HIV infection
时间窗: week 0-26
HIV acquisition at or before week 26 by a participant who was HIV negative at enrolment
A clinical decision to discontinue the vaccine regimen for an adverse event that is considered related to product
时间窗: week 0-48
A clinical decision to discontinue the vaccine regimen for an adverse event that is considered related to product
A clinical decision to discontinue PrEP regimen for an adverse event that is considered related to product
时间窗: week 0-26
A clinical decision to discontinue PrEP regimen for an adverse event that is considered related to product
次要结局
- Discontinuation or interruption of PrEP(week 0-26)
- Serious adverse events(week 0-74)
- Other clinical and laboratory adverse events(week 0-74)
- Binding antibodies(week 0-74)
- Resistance mutations to tenofovir and emtricitabine(week 0-74)
- Number of PrEP pills missed(week 0-26)
- Tenofovir level in urine(week 0-26)
- Tenofovir level in red blood cells(week 0-26)
- Number of PrEP Pills dispensed(week 0-26)
- Grade 3 and worse solicited clinical and laboratory adverse events(within 7 days of receiving vaccine injection)
- Discontinuation or interruption of vaccine regimen(week 0-74)