A Randomized Single-blind Placebo-controlled Study to Evaluate the Safety and Immunogenicity of Three Candidate HIV-1 Vaccines, pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv, Administered in Combination to Healthy HIV 1 Uninfected Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Safety
研究概览
简要总结
This is a randomised, placebo-controlled, single-blind study designed to evaluate the safety and immunogenicity of three novel HIV vaccines.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males or females, as assessed by a medical history, physical examination and laboratory tests.
- •Aged at least 18 years on the day of screening and no greater than 50 years on the day of the first vaccination.
- •Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
- •In the opinion of the principal investigator or designee, the volunteer has understood the information provided. Written informed consent must be given before any study-related procedures are performed.
- •Willing to undergo HIV-1 testing, HIV-1 counselling and receive HIV-1 test results.
- •If heterosexually active female; using an effective method of contraception (e.g. hormonal contraception, diaphragm, intra-uterine device (IUD), condoms, anatomical sterility in self or partner) from 14 days prior to the first vaccination until at least 6 weeks after the last vaccination; all female volunteers must be willing to undergo urine pregnancy tests at time points specified in the protocol.
- •If heterosexually active male; willing to use an effective method of contraception (condoms; anatomical sterility in self or partner) from the day of the first vaccination until 6 weeks after the last vaccination.
- •Willing to forgo donations of blood during the study.
排除标准
- •Any clinically significant acute or chronic medical condition that is considered progressive or, in the opinion of the principal investigator or designee, would make the volunteer unsuitable for the study.
- •Any of the following abnormal laboratory parameters listed below:
- •Haematology
- •Haemoglobin < 10.0 g/dl
- •Absolute Neutrophil Count (ANC) ≤ 1000 /mm3 (≤ 1 x 109 /l)
- •Absolute Lymphocyte Count (ALC) ≤ 600 /mm3 (≤ 1 x 109 /l)
- •Platelets ≤100,000 /mm3, ≥ 550,000 /mm3 (≤ 90 /l, ≥ 550 /l) Biochemistry
- •Creatinine > 1.3 x ULN
- •Aspartate aminotransferase (AST) > 2.5 x ULN
- •Alanine aminotransferase (ALT) > 2.5 x ULN Urinalysis
- •Abnormal dipstick confirmed by microscopy
- •Reported high-risk behaviour for HIV infection. High-risk behaviour for HIV-1 infection is defined as follows. Within the previous 6 months the volunteer has:
- •Had unprotected vaginal or anal sex with a known HIV-infected person or a casual partner (i.e., no continuing, established relationship)
- •Engaged in sex work for money or drugs
- •Used injection drugs
- •Acquired one of the following sexually transmitted disease (STD); Chlamydia, gonorrhoea and syphilis.
- •Confirmed HIV-1 or HIV-2 infection.
- •If female, pregnant or planning a pregnancy within 6 weeks after last vaccination; or lactating.
- •Receipt of live attenuated vaccine within the previous 60 days (live attenuated flu vaccine within 14 days) or planned receipt within 60 days after vaccination with Investigational Product or receipt of other vaccine within the previous 14 days or planned receipt within14 days after vaccination with Investigational Product.
- •Receipt of blood transfusion or blood products within the previous 6 months.
- •Participation in another clinical trial of an Investigational Product currently, within the previous 3 months or expected participation during this study.
- •Receipt of any investigational HIV vaccine within the last 6 years.
- •History of severe or very severe local or systemic reactogenicity events, or history of severe or very severe allergic reactions.
- •Confirmed diagnosis of hepatitis B virus (surface antigen, HBsAg), hepatitis C virus (HCV antibodies) or active syphilis.
- •Smallpox vaccination within the previous 3 years (smallpox vaccination prior to 3 years should be documented but is not an exclusion criterion).
- •Major psychiatric illness including any history of schizophrenia or severe psychosis, bipolar disorder requiring therapy, suicidal attempt or ideation in the previous 3 years.
研究组 & 干预措施
Stage 3 placebo
Time-course matched to vaccinations (n=2)
干预措施: Placebo (Other)
Stage 4 placebo
Time-course matched to vaccinations (n=2)
干预措施: Placebo (Other)
Stage 3
Three doses of pSG2.HIVconsv DNA followed by boost with high dose ChAdV63.HIVconsv followed by boost with MVA.HIVconsv at week 0,4,8,12 and 20, respectively (n=8). Followed up at 6, 12 and 24 months after last vaccination.
干预措施: ChAdV63.HIVconsv high dose. (Biological)
Stage 3
Three doses of pSG2.HIVconsv DNA followed by boost with high dose ChAdV63.HIVconsv followed by boost with MVA.HIVconsv at week 0,4,8,12 and 20, respectively (n=8). Followed up at 6, 12 and 24 months after last vaccination.
干预措施: pSG2.HIVconsv (Biological)
Stage 4
Three doses of pSG2.HIVconsv DNA followed by boost with MVA.HIVconsv followed by boost with high dose ChAdV63.HIVconsv at weeks at week 0,4,8,12 and 16, respectively (n=8).
干预措施: ChAdV63.HIVconsv high dose. (Biological)
Stage 4
Three doses of pSG2.HIVconsv DNA followed by boost with MVA.HIVconsv followed by boost with high dose ChAdV63.HIVconsv at weeks at week 0,4,8,12 and 16, respectively (n=8).
干预措施: pSG2.HIVconsv (Biological)
Stage 2 Placebo
Time-course matched to vaccinations (n=2)
干预措施: Placebo (Other)
Stage 1.
The first stage will start from a low and well tolerated, but likely less immunogenic dose of ChAdV63.HIVconsv (n=2).
干预措施: ChAdV63.HIVconsv low dose. (Biological)
Stage 2
The highest dose of ChAdV63.HIVconsv followed by boost with MVA.HIVconsv at week 0 and 8, respectively (n=8). Followed up at 6,12 and 24 months after last vaccination.
干预措施: ChAdV63.HIVconsv high dose. (Biological)
Stage 4
Three doses of pSG2.HIVconsv DNA followed by boost with MVA.HIVconsv followed by boost with high dose ChAdV63.HIVconsv at weeks at week 0,4,8,12 and 16, respectively (n=8).
干预措施: MVA.HIVconsv (Biological)
Stage 3
Three doses of pSG2.HIVconsv DNA followed by boost with high dose ChAdV63.HIVconsv followed by boost with MVA.HIVconsv at week 0,4,8,12 and 20, respectively (n=8). Followed up at 6, 12 and 24 months after last vaccination.
干预措施: MVA.HIVconsv (Biological)
Stage 2
The highest dose of ChAdV63.HIVconsv followed by boost with MVA.HIVconsv at week 0 and 8, respectively (n=8). Followed up at 6,12 and 24 months after last vaccination.
干预措施: MVA.HIVconsv (Biological)
结局指标
主要结局
Safety
时间窗: Actively collected data throughout the study until 6 months after the last vaccination
Proportion of volunteers who develop a grade 3 or 4 local reaction.
次要结局
- Immunogenicity(Stage 1; screen, 0, 1, 2, 4, 8, 16, 28 wk. Stage 2; screen, 0, 1, 2, 4, 8, 9, 12, 20, 28 wk. Stage 3; screen, 1, 8, 12, 13, 14, 20, 21, 22, 28 wk. Stage 4; screen, 0, 8, 12, 13, 16, 17, 18, 24, 28 wk post vac. Stage 2 & 3: 6,12,24 mth after last vaccine)
- Immunogenicity(Samples will be collected at every visit pre- and post vaccination)