Phase I/II Open-label Randomized Multicenter Trial to Assess Immunogenicity and Safety of 4 Prime-boost Combinations of HIV Vaccine Candidates (MVA HIV-B/LIPO-5; LIPO-5/MVA HIV-B; GTU®-MultiHIV B/LIPO-5; GTU®-MultiHIV B/MVA HIV-B) in Healthy Volunteers at Low Risk of HIV Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 2
- 主要终点
- Evaluation of the Safety of MVA HIV-B at Week 2 in Arm 1
研究概览
简要总结
The development of a safe and effective HIV-1 vaccine strategy would probably be the best solution for the ultimate control of the worldwide AIDS pandemic. Heterologous prime-boost immunisations are today considered promising HIV prophylactic vaccine strategies. It is thus relevant to pursue the development of different candidate vaccines in prime-boost vaccine strategies to identify the most promising prime-boost combinations and to integrate scientific inquiry into trial protocols from the beginning to maximize learning opportunities.
详细描述
Phase I/II, multicenter, national, open-label, randomized trial HIV including 4 prophylactic prime-boost HIV vaccines strategies:
Volunteers are randomly allocated in a 1:1:1:1 ratio at trial entry to 4 parallel arms with the following prime-boost strategies:
Arm 1. MVA HIV-B primes at Week 0 and Week 8 + LIPO-5 boosts at Week 20 and Week 28 Arm 2. LIPO-5 primes at Week 0 and Week 8 + MVA HIV-B boosts at Week 20 and Week 28 Arm 3. GTU-MultiHIV B primes at Week 0, Week 4 and Week 12 + LIPO-5 boosts at Week 20 and Week 28 Arm 4. GTU-MultiHIV B primes at Week 0, Week 4 and Week 12 + MVA HIV-B boosts at Week 20 and Week 28
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
- 21 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Written and signed informed consent
- •Subject at low risk to contract HIV i.e.
- •no history of injecting drug use in the previous ten years;
- •no gonorrhea or syphilis in the last six months;
- •no high risk partner (e.g. injecting drug user, HIV positive partner) either currently or within the past six months ;
- •no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known/presumed to be HIV negative ;
- •no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
- •Available for follow-up for the duration of the study (56 weeks from screening)
- •Willing to undergo a HIV test
- •Willing to undergo a genital infection screen
- •If heterosexually active female, using an effective method of contraception with partner (combined oral contraceptive pill; injectable contraceptive; contraceptive implant/patch; IntraUterine Contraceptive Device (IUCD); consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination
- •If heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
- •Subject registered in French Health ministry computerised file and authorised to participate in a clinical trial
- •Subject covered by Health Insurance
排除标准
- •Clinically relevant abnormality on history or examination including history of:
- •uncontrolled infection;
- •autoimmune disease;
- •immunodeficiency or use of immunosuppressive drugs within 3 months prior to screening;
- •chronic diseases requiring long-term treatment whose interruption during the trial has no impact on the health status in the short or long-term
- •Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days prior to W0
- •Planned receipt of other vaccines than those planned by the protocol and those recommended in France (excluding live attenuated vaccines) during the trial follow-up (reference : Weekly Epidemiological Newsletter 14-15 dated on April 10th, 2012 (Bulletin Epidémiologique hebdomadaire 14-15 / 10 avril 2012))
- •Receipt of blood products or immunoglobin within 4 months prior to screening
- •History of severe local or general reaction to vaccination defined as
- •local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours
- •general: fever ≥ 39.5°C within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
- •Positive for ANA antibodies at a titer considered clinically significant: titer ≥ local cut-off associated with positive anti-native DNA and extractable nuclear antigen antibodies
- •HIV-1 or HIV-2 positive or indeterminate at screening
- •Woman expecting to conceive during the study period
- •Pregnant or breastfeeding woman
- •Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, which could interfere with the interpretation of the trial results or compromise the health of the volunteers
- •Clinically significant grade 1 routine laboratory parameters
- •Grade 2 or above routine laboratory parameters
- •Known hypersensitivity to aminoglycosides and eggs (as used in the vaccine production processes)
- •Known hypersensitivity to one of the trial vaccine components, the metabolites or formulation excipients
- •Anticipated non-compliance with the protocol
- •Participation in another clinical trial with an on-going exclusion period at screening
- •Participation in a HIV preventive vaccine clinical trial (unless participant were randomized in placebo arm)
- •Subject under legal guardianship or incapacitation
- •Subject who is an active blood donor and unwilling to interrupt blood donations during the his/her participation in the trial
研究组 & 干预措施
MVA HIV-B and LIPO-5 vaccines
MVA HIV-B primes 0,5 milliliter (mL) Intramuscular at Week 0 and Week 8 LIPO-5 1mL Intramuscular boosts at Week 20 and Week 28
干预措施: MVA HIV-B (MVATG17401) (Biological)
LIPO-5 and MVA HIV-B vaccines
LIPO-5 primes 1mL intramuscular at Week 0 and Week 8 and MVA HIV-B 0,5mL intramuscular boosts at Week 20 and Week 28
干预措施: MVA HIV-B (MVATG17401) (Biological)
GTU-MultiHIV B and MVA HIV-B vaccines
GTU-MultiHIV B 0,5mL intramuscular via Biojector 2000 and 0,5mL intradermic primes at Week 0, Week 4 and Week 12 and MVA HIV-B 0,5mL intramuscular boosts at Week 20 and Week 28
干预措施: MVA HIV-B (MVATG17401) (Biological)
GTU-MultiHIV B and LIPO-5 vaccines
GTU-MultiHIV B 0,5mL intramuscular via Biojector 2000 and 0,5mL intradermic primes at Week 0, Week 4 and Week 12 and LIPO-5 1mL intramuscular boosts at Week 20 and Week 28
干预措施: GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots (Biological)
GTU-MultiHIV B and MVA HIV-B vaccines
GTU-MultiHIV B 0,5mL intramuscular via Biojector 2000 and 0,5mL intradermic primes at Week 0, Week 4 and Week 12 and MVA HIV-B 0,5mL intramuscular boosts at Week 20 and Week 28
干预措施: GTU®-MultiHIV B: 0.5 mL IM via Biojector® 2000 and 0.5mL IntraDermic, 3 shots (Biological)
GTU-MultiHIV B and LIPO-5 vaccines
GTU-MultiHIV B 0,5mL intramuscular via Biojector 2000 and 0,5mL intradermic primes at Week 0, Week 4 and Week 12 and LIPO-5 1mL intramuscular boosts at Week 20 and Week 28
干预措施: LIPO-5 (Biological)
LIPO-5 and MVA HIV-B vaccines
LIPO-5 primes 1mL intramuscular at Week 0 and Week 8 and MVA HIV-B 0,5mL intramuscular boosts at Week 20 and Week 28
干预措施: LIPO-5 (Biological)
MVA HIV-B and LIPO-5 vaccines
MVA HIV-B primes 0,5 milliliter (mL) Intramuscular at Week 0 and Week 8 LIPO-5 1mL Intramuscular boosts at Week 20 and Week 28
干预措施: LIPO-5 (Biological)
结局指标
主要结局
Evaluation of the Safety of MVA HIV-B at Week 2 in Arm 1
时间窗: Visit Week 2
Count of participants without any grade 3 or 4 adverse events (clinical or biological) related to MVA-vaccine immunisation, reported from Week 0 to Week 2 in arm 1
To Discard Vaccine Strategies With an Insufficient Level of Immunogenicity, Defined by HIV-specific IFN-γ-ELISPOT Responses, Among 4 HIV Prophylactic Prime-boost Combinations in Healthy Volunteers at Low Risk of HIV Infection
时间窗: Visit Week 30
Count of participants with a HIV-specific Interferon-gamma Enzyme Linked Immunosorbent SPOT (IFN-γ ELISPOT) response in each of the 4 arms, defined by a positive response to at least one of the stimulating HIV peptide pools (15-mer pools covering Env, Gag, Pol, and Nef) measured in stimulated Peripheral Blood Mononuclear Cell (PBMC) by a standard IFN-γ ELISPOT assay at Week 30, i.e. 2 weeks after the last vaccine immunisation.
次要结局
- To Assess the Tolerance of Each Prime-boost Combination(Between week 0 and week 52)
- To Assess for Each Prime-boost Combination the Type of Vaccine-induced T Cell Response(At W2, W10 and W22 for reporting groups : MVA HIV-B/LIPO-5 and LIPO-5/MVA HIV-B. And at W2, W6, W14 and W22 for reporting groups : GTU-MultiHIV B/LIPO-T and GTU-MultiHIV B/MVA HIV-B.)