A Phase I/II Randomized Placebo Controlled Trial to Evaluate the Safety and Immunogenicity of Sudan Ebolavirus Vaccines in Uganda
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 2,121
- 主要终点
- Incidence of solicited, unsolicited adverse and serious adverse events (safety)
研究概览
简要总结
The TokomezaPlus Ebola trial is a phase I/II double blind randomised clinical trial designed to assess the safety and immunogenicity of candidate SUDV vaccines in Uganda during the inter outbreak period. Uganda is prone to Ebola virus disease outbreaks especially those caused by the Ebola Sudan (SUDV) species. TokomezaPlus Ebola Vaccine trial protocol has two main components: a) Safety b) Immunogenicity and is designed to create a living protocol that will be used to study the safety and immunogenicity of SUDV-candidate vaccines in the East African EVD-prone countries.
详细描述
The Sudan ebolavirus and the Zaire ebolavirus are classified as different species, and vaccines and monoclonal antibodies that are effective against Zaire ebolavirus disease are unlikely to be of any use against SUVD. But, the epidemiology of SUVD is thought to be similar to that of Zaire ebolavirus disease.
There is an urgent need to test the safety and immunogenicity of the candidate vaccine(s) developed against Sudan ebolavirus. Once safety and immunogenicity (including extended immunogenicity) have been proven, these vaccines could be deployed for future outbreaks as part of the response.
OBJECTIVES Phase 1 Objectives
- To determine the safety of rVSV-SUDV candidate SUDV vaccine among healthy volunteers
- To determine the immunogenicity of rVSV-SUDV candidate SUDV vaccine
Phase 2 Primary objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blinding to be done
入排标准
- 年龄范围
- 6 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers aged 18-50 years from study communities
- •Healthy volunteers with a permanent home address
- •Able and willing to complete and provide written informed consent. In case the participant cannot read or write, the procedures must be explained to him/her and informed consent must be witnessed by a literate third party not involved with the conduct of the study
- •Participant must pass the informed consent test of understanding (TOU)
- •Participant must be healthy in the investigator's clinical judgement on the basis of medical history, physical examination, vital signs and point of care tests (where applicable) performed at screening
- •If female of child-bearing potential and heterosexually active, practice of adequate contraception for 28 days prior to injection, negative pregnancy test on the day of vaccination, and agreement to continue adequate contraception until 90 days after vaccination
- •Male participants are eligible to participate in the study if they agree to use a male condom during any heterosexual intercourse with a female of childbearing potential until 90 days after vaccination
- •Healthy volunteers aged 6 years-65 years from study communities. Individuals with comorbidities assessed as stable will be allowed to participate
- •With a permanent home address
- •Able and willing to complete and provide written informed consent or assent as applicable. In case the participant cannot read or write, the procedures must be explained to him/her, and informed consent must be witnessed by a literate third party not involved with the conduct of the study.
- •Participant must pass the informed consent or assent test of understanding (TOU)
- •Participant must be healthy according to the investigator's clinical judgement on the basis of medical history, physical examination, vital signs and point of care tests (where applicable) performed at screening
- •If female of child-bearing potential and heterosexually active, practice of adequate contraception for 28 days prior to injection, negative pregnancy test on the day of vaccination, and agreement to continue adequate contraception until 180 days after vaccination
- •Male participants are eligible to participate in the study if they agree to abstain from any heterosexual intercourse with a female of childbearing potential or must agree to use a male condom
排除标准
- •History of confirmed ebola virus diseases (SUDV, EBOV or BUDV)
- •Unwillingness of female participants to use effective contraception
- •Participation in an interventional clinical trial within 90 days of participation in this trial
- •Prior vaccination with any Ebola vaccine
- •Breastfeeding or planning to conceive within 2 months following study vaccination
- •Has history of fever (>100.4ºF/38.0ºC) within 48 hours prior to enrolment into the study
- •Received systemic corticosteroids exceeding physiologic replacement doses (~5 mg/d prednisone equivalent) within 14 days prior to study entry
- •Received any live virus vaccine within 30 days or any non-live virus vaccine within 14 days prior to study entry
- •Has a known allergy/sensitivity or contraindication to investigational vaccines or its/their excipients?
- •History of malignancy ≤5 years
- •Major surgery within the 4 weeks prior to screening or planned major surgery through the course of the study (from screening until completion of the study)
- •Presence of any condition that can interfere with the subject's participation for the full duration of the trial.
- •HIV positive
- •Hepatitis B positive
- •History of confirmed SUDV
- •Unwillingness of female participants to use effective contraception
- •Participation in an interventional clinical trial within 90 days of start of this trial
- •Prior vaccination with any Ebola vaccine
- •Breastfeeding or planning to conceive within 2 months following study vaccination
- •Has history of fever (>100.4ºF/38.0ºC) within 48 hours prior to vaccination
- •Received systemic corticosteroids exceeding physiologic replacement doses (~20 mg/d prednisone or equivalent) for 14 days within a month prior to study entry.
- •Immunosuppressive medication within 3 months
- •Received any live virus vaccine within 30 days or any non-live virus vaccine within 14 days prior to study entry
- •Has a known allergy/sensitivity or contraindication to investigational vaccines or its/their excipients?
- •History of malignancy ≤5 years
- •Major surgery within the 4 weeks prior to screening or planned major surgery through the course of the study (from screening until completion of the study)
- •Presence of any condition that can interfere with the subject's participation for the full duration of the trial
结局指标
主要结局
Incidence of solicited, unsolicited adverse and serious adverse events (safety)
时间窗: 72 months
The adverse events (AE) and serious adverse events (SAE) will be evaluated to determine the link to the investigational product. They will then be classified as possibly, probably and definitely related to the investigational products
Vaccine-specific antibody concentration (immunogenicity) measured as optical density that will be converted to concentration
时间窗: 72 months
The vaccine specific antibody concentration will be assessed through specific laboratory procedures that make use of Nunc Maxisorp flat bottom plates will be coated with Ebola GP in a coating buffer. Heat inactivated serum or plasma from study participants (either diluted and or undiluted) or treated plasma sample from SUDV convalescent individuals (Positive control) or Mouse anti SUDV GP mAb (positive control) will be added to the plates and incubated. The plates will be washed and HRP goat anti-human IgG antibody and or HRP goat anti-human IgM antibody and or HRP goat anti-mouse IgG Fc or HRP goat anti-mouse IgM Fc will be added. The plates will be washed and tetramethylbenzidine (TMB) 1 component microwell peroxidase substrate added. The reaction will be stopped after about 20 minutes with hydrochloric acid. The plate's absorbance will be read at 450 nm and 630 nm. A standard curve/line will be drawn and convert the optical density to concentration
Vaccine specific antibody neutralization capability (immunogenicity) represented as proportion of neutralization
时间窗: 72 months
Vero cells will be incubated in Eagles Minimum Essential Medium with fetal bovine serum and penicillin/streptomycin (R10) and maintained at 37°C and 5% CO2 humidified incubator. The cells will be plated onto a 96 well black flat bottomed culture plate. Study participant, positive (obtained from SUDV convalescent individuals and pre-treated) and negative controls heat inactivated serum samples will be diluted and mixed with single round infecting recombinant vesicular stomatitis virus expressing SUDV GP and firefly luciferase at room temperature with appropriate controls. The virus and serum sample mixture will be added to the plated vero cells and incubated for up to 24 hours. The virus and serum sample will be removed and vero cells lysed. Luciferase activating reagent will be added and the luminescence will be read using a luminescence plate reader. The proportion of neutralisation will be evaluated using appropriate controls (rVSV without serum).
Vaccine-induced T cell responses (immunogenicity) determined as spot forming units per one million cells.
时间窗: 72 months
This will be done as per the standard operating procedures. IFN-γ precoated ELISPOT plates will be washed and blocked using serum. Thawed and rested PBMC will be plated, stimuli (peptides to ebola GP, appropriate positive and negative controls) added and incubated for 12 to 24 hours. The plates will be emptied and washed after incubation. Diluted enzyme-conjugate detection IFN-γ antibody will be added and incubated. The plates will be washed \& substrate added and allowed to develop for about 20 minutes. The development will be stopped by rinsing the plates in copious amounts of deionised water. The plates will be allowed to air dry in the dark and read using an ELISPOT reader within 12 hours. The results will be determined as spot forming units per one million cells
次要结局
- Durability of the immune response measured up to 72 months quantitively by assessing the antibody concentration and qualitatively by assessing the antibody neutralization capacity. Curves will be drawn to represent immune responses against time(72 months)
研究者
Bruce J Kirenga
Prof
Makerere University