A Randomised, Controlled, Double-blind, Parallel Group, Single Center Phase Ib Trial to Assess Safety, Reactogenicity and Immunogenicity of a Candidate Dual-stage Malaria Vaccine, SumayaVac-1 (MSP-1 With GLA-SE as Adjuvant) in Healthy Malaria Exposed Adults of African Origin Aged 18-45 Years
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Local and systemic unsolicited reactogenicity after vaccination
研究概览
简要总结
Malaria remains a major infectious disease causing a heavy burden of mortality and morbidity in populations living in tropical and subtropical regions. Large, international research efforts have been invested into the development of anti-malaria vaccination strategies, however, currently there is only one malaria vaccine approved for use in the pediatric population, which provides a moderate and short-lived protection. Therefore, there is a need to develop a malaria vaccine that will be essential to further strengthen malaria control measures in future.
A Phase Ia trial with the same IMP (SumayaVac-1 vaccine developed using a full-length recombinant MSP-1 administered along with the adjuvant GLA-SE) in Caucasians in Heidelberg, Germany, proved to be well tolerated and safe. However, a Phase Ib clinical trial on healthy participants residing in a malaria endemic country would be essential to evaluate the safety and reactogenicity in the target population. The project aims to investigate the safety, reactogenicity, immunogenicity of the candidate malaria vaccine, SumayaVac-1 (SUM-101) in 40 healthy participants (men and women) of African origin in Bagamoyo, Tanzania.
详细描述
Objectives:
To evaluate in healthy adults of African origin previously exposed to the malaria parasite receiving SumayaVac-1 (SUM-101) versus rabies control (Verorab®) vaccine:
Primary Objectives
- Safety and reactogenicity of SumayaVac-1 (SUM-101).
- Immunogenicity of SumayaVac-1 (SUM-101).
Secondary Objectives
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This trial will be conducted in a double-blinded manner. Namely, the participants, site staff, sponsor staff, the study monitor(s) and the trial statistician will be blinded to the treatment allocation. The independent statistician and the pharmacist are not blind throughout the study.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Written informed consent obtained before any study procedure.
- •Literate participants aged 18-45 years of African origin.
- •Female participants practicing contraception from 4 weeks before 1st immunization and both female and male participants willing to practice contraception up to 12 weeks after the last immunization.
- •Available to participate in follow-up for the duration of the study.
- •Contactable by phone during the whole study period.
- •At least two years residence in the Bagamoyo district or nearby districts in Coastal and Dar-es-Salaam regions and planning to reside there for at least 9 more months.
- •Agreement to provide personal contact information and contact information of another household member or close friend.
- •Female participants must be willing to avoid pregnancy if selected for participation in the trial and to undergo multiple serum pregnancy testing.
- •Confirmation of understanding of design, procedures, risk and benefits of the study in a test with maximum of two attempts.
- •General good health based on assessment of medical history and clinical examination.
排除标准
- •Previous participation in any malaria vaccine trial in the last 3 years.
- •Participation in any other clinical trial involving investigational medicinal products within 30 days prior to the screening assessment.
- •Previous history of drug or alcohol abuse interfering with normal social function within one year prior to enrolment.
- •Previous vaccination with a rabies vaccine.
- •Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating drugs) during the 13 weeks preceding the screening visit or during the study period.
- •Known hypersensitivity to any of the vaccine components (adjuvant or protein) or anti-malarial treatments.
- •Body mass index (BMI) of <18 or >30 Kg/m
- •Participants unable to be closely followed for social, geographic or psychological reasons.
- •Any vaccination from 4 weeks prior to the 1st vaccination and (none planned) up to 6 weeks after the 3rd vaccination.
- •Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the participants.
- •Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, clinically significant arrhythmias, left bundle branch block, secondary or tertiary A-V (atrio-ventricular) heart block.
- •Any clinically significant laboratory values at screening outside of normal ranges for study participants.
- •Malaria positivity at screening (microscopy or qPCR positive).
- •Positive HIV, HBV or HCV tests.
- •For females: Positive pregnancy test or actively breast feeding.
结局指标
主要结局
Local and systemic unsolicited reactogenicity after vaccination
时间窗: Recorded up to 28 days after each vaccination
Local and systemic unsolicited reactogenicity recorded after each vaccination (done on Day 0, Day 28 and Day 56 up to 28 days later to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Local and systemic adverse events (AEs) at least possibly related to the IMP after vaccination
时间窗: Recorded up to 7 days after each vaccination
Local and systemic solicited adverse events (AEs) at least possibly related to the investigational medicinal product (IMP) recorded after each vaccination (done on Day 0, Day 28 and Day 56 up to 7 days later to evaluate safety and reactogenicity of SumayaVac-1 (SUM-101)
Any serious adverse events (SAE) occurring after the 1st vaccination until the participant's last visit
时间窗: Recorded from after 1st vaccination (Day 0 post-vaccination) until the participant's last visit (Day 140)
Any serious adverse events (SAE) occurring after the 1st vaccination until the participant's last visit to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Changes in laboratory safety parameters between baseline and 28 days after vaccination
时间窗: Changes recorded between baseline (Day 0 before 1st vaccination) to 28 days after each vaccination
Changes in laboratory safety parameters as defined in the protocol for every participant between baseline (Day 0 before 1st vaccination) to 28 days after each of the vaccinations to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Longevity of antibody responses to SumayaVac-1 (SUM-101) by ELISA
时间窗: Titres assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit)
Longevity of antibody responses to SumayaVac-1 (SUM-101) by ELISA for all participants at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16) and Day 140 (Week 20), to evaluate the humoral immunogenicity
Fold change of antibody responses to SumayaVac-1 (SUM-101) in comparison to baseline
时间窗: Fold changes assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit)
Fold change of antibody responses to SumayaVac-1 (SUM-101) by ELISA in comparison to baseline (Day 0 pre-vaccination) for all participants to Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16) and Day 140 (Week 20), to evaluate the humoral immunogenicity
Changes in laboratory safety parameter prior to vaccination to 28 days after that vaccination
时间窗: Changes prior to each vaccination to 28 days after proceeding with vaccination
Changes in laboratory safety parameters as defined in the protocol for every participant between values recorded just prior to each vaccination (on Day 0, Day 28 and Day 56) and values found 28 days after proceeding with vaccination to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
次要结局
- Evaluation of complement fixation, activation and/or membrane attack complex (MAC) formation of vaccine-induced antibodies(Changes assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit))
- Evaluation of antibody-dependent respiratory burst (ADRB) activity of vaccine-induced antibodies(Changes assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit))
- Evaluation of antibody-dependent cellular cytotoxicity (ADCC-NK cells) activity of vaccine-induced antibodies(Changes assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit))
- Evaluation of the opsonic phagocytosis activity of vaccine induced antibodies(Changes assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit))
- Evaluation of immune-mediated growth inhibition activity on Plasmodium falciparum asexual blood stage cell lines(Changes assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit))
- Comparison of MSP-1 IgG antibody concentrations by ELISA(Antibody concentrations compared between Day 0 (pre-vaccination) up to Day 84)