A Single Centre, Double-blind, Double-dummy Placebo-controlled, Randomised Phase Ib Study to Evaluate the Safety & Immunogenicity of the Candidate Chikungunya Vaccine ChAdOx1 Chik & the Zika Vaccine ChAdOx1 Zika in Healthy Adults in Mexico
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Assess the safety profile and tolerability of ChAdOx1 Chik and ChAdOx1 Zika in healthy participants: occurrence of solicited systemic reactogenicity signs and symptoms
研究概览
简要总结
Phase Ib, single centre, double-blind, double-dummy placebo-controlled, randomised, stepwise dose escalated, vaccine trial to assess the safety and immunogenicity of the candidate ChAdOx1 Chik and ChAdOx1 Zika vaccines, given as a standalone vaccines or in co-administration. Healthy volunteers aged 18-50 years old, residents of the metropolitan area of Monterrey (Mexico), will be recruited as participants
详细描述
This trial consists of 4 intervention arms according to the vaccination product: 1) ChAdOx1 Chik, 2) ChAdOx1 Zika, 3) ChAdOx1 Chik and ChAdOx1 Zika as contralateral co-administration, and 4) placebo. There will be a total of 120 participants divided in ten study groups with 12 participants per group (Table 5.1). Groups 1 to 3 will receive ChAdOx1 Chik + placebo administered contralaterally, Groups 4 to 6 will receive ChAdOx1 Zika + placebo administered contralaterally, and Groups 7 to 9 will receive both ChAdOx1 Chik and ChAdOx1 Zika administered contralaterally. Group 10 will receive placebo in both arms.
Enrolment into this study will be implemented in a step-wise dose escalation manner. Participants will be first recruited into the vaccination groups at the lowest dose (Groups 1, 4 and 7). It is only after completion of these low dose groups and upon satisfactory interim clinical safety reviews that participants will be enrolled into the mid dose groups (Groups 2, 5 and 8). Participants in the high dose groups (Groups 3, 6 and 9) will be enrolled last, after completion and interim clinical safety reviews from the mid dose groups. Participants allocated to the Placebo group (Group 10) will be evenly distributed across the dose escalation model.
Randomisation procedures will be implemented accordingly, at a ratio of 3:3:3:1 for each of the four intervention arms.
The study involves a total of 9 visits (screening inclusive) and follow up will be undertaken for 6 months after vaccination day
Innovate UK (project number 971557)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Double (Participant, Care Provider)
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 men aged 18 to 50 (inclusive) years at the time of screening.
- •Healthy women aged 18 to 50 (inclusive) of child-bearing potential who agree to practice continuous effective contraception (see below) during the study and test negative for pregnancy on the day(s) of screening and vaccination.
- •Are residents of the metropolitan area of Monterrey, Nuevo León.
- •Provide written informed consent for participation in the study.
- •Able and willing (in the Investigator's opinion) to comply with all study requirements.
- •Agreement to inform study team of any impending vaccinations either before or during participation in the study.
- •Agreement to refrain from blood donation during the course of the study.
- •Agreement to refrain from receipt of any alphavirus or flavivirus vaccine throughout the duration of the study (e.g. investigational or licensed Yellow Fever, Japanese Encephalitis, Tick Borne Encephalitis or Dengue virus vaccines).
排除标准
- •Participation in another clinical trial in the 30 days preceding enrolment or during the study period.
- •Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccine, Chikungunya virus vaccine, Zika virus vaccine, Dengue virus vaccine).
- •Prior receipt of any vaccines administered ≤30 days before enrolment and/or planned during the during the study.
- •Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Any history of anaphylaxis in relation to vaccination.
- •History of autoimmune disease.
- •Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
- •Pregnancy, lactation or willingness/intention to become pregnant during the study.
- •History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
- •History of serious psychiatric condition likely to affect participation in the study
- •Bleeding disorder (eg. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
- •Any other serious chronic illness requiring hospital specialist supervision at present or during the last 6 months.
- •Suspected or known current alcohol abuse. For men, intake greater than 5 drinks on a single occasion or more than 15 drinks per week; and for women, more than 4 drinks on a single occasion or more than 8 drinks per week. One drink =14 grams of pure alcohol.
- •Suspected or known injecting drug abuse in the 5 years preceding enrolment.
- •Seropositive for hepatitis B surface antigen (HBsAg).
- •Seropositive for hepatitis C virus (antibodies to HCV).
- •Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis.
- •Has history of chronic or acute severe neurologic condition. Including: Neurologic and Neuroinflammatory Disorders: ADEM, including site specific variants, Cranial Nerve Disorders (including paralyses/paresis), GBS (including Miller Fisher Syndrome and other variants), Immune-mediated Peripheral Neuropathies and Plexopathies, Optic Neuritis, Multiple Sclerosis, Narcolepsy, Transverse Myelitis, meningitis, or meningoencephalitis.
- •Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
- •Seropositivity or cross-reactivity to Chikungunya virus, Zika virus or Dengue virus on screening tests.
结局指标
主要结局
Assess the safety profile and tolerability of ChAdOx1 Chik and ChAdOx1 Zika in healthy participants: occurrence of solicited systemic reactogenicity signs and symptoms
时间窗: 7 days post vaccination
Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination.
Assess the safety profile and tolerability of ChAdOx1 Chik and ChAdOx1 Zika in healthy participants: occurrence of local reactogenicity signs and symptoms
时间窗: 7 days post vaccination
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination.
Assess the safety profile and tolerability of ChAdOx1 Chik and ChAdOx1 Zika in healthy participants: occurrence of unsolicited adverse events
时间窗: 28 days post vaccination
Occurrence of unsolicited adverse events for 28 days following vaccination
Assess the safety profile and tolerability of ChAdOx1 Chik and ChAdOx1 Zika in healthy participants: occurrence of serious adverse events during the whole study duration
时间窗: 6 months post vaccination
Occurrence of serious adverse events during the whole study duration
Assess the safety profile and tolerability of ChAdOx1 Chik and ChAdOx1 Zika in healthy participants through standard blood tests (full blood count, liver and kidney function tests)
时间窗: 28 days post vaccination
Change from baseline for safety laboratory measures (haematology and biochemistry blood results)
次要结局
- Assess the humoral immunogenicity of the candidate vaccines ChAdOx1 Chik and ChAdOx1 Zika via PRNT50(6 months post vaccination)
- Assess the humoral immunogenicity of the candidate vaccines ChAdOx1 Chik and ChAdOx1 Zika via IgG ELISA antibody titres(6 months post vaccination)