A Randomized, Open Label, Single Centre, Phase 2 Trial of the Malaria Vaccine, R21/Matrix-M, to Assess Safety and Immunogenicity of the Vaccine in Thai Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 127
- 试验地点
- 1
- 主要终点
- Occurrence of Unsolicited Adverse Events (AEs), According to the Medical Dictionary for Regulatory Activities (MedRA) Classification.
研究概览
简要总结
Malaria remains one of the leading causes of morbidity and mortality worldwide. Plasmodium falciparum is a complex pathogen with numerous immune evasion mechanisms which has added layers of complexity to the development of safe and protective vaccines. There remains an urgent need to identify and develop more protective and more affordable vaccine candidates that could achieve the World Health Organization (WHO) goal of 75% efficacy against clinical malaria.
R21 is a novel pre-erythrocytic candidate malaria vaccine. R21 includes Hepatitis B surface antigen (HBsAg) fused to the C-terminus and central repeats of the circumsporozoite protein of P. falciparum (CSP), which self-assemble into virus-like particles in yeast. R21 lacks the excess HBsAg found and comprises only fusion protein moieties.
R21/MatrixM (MM) had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the serious adverse events were attributed to the vaccine. At one year, vaccine efficacy remained high, at 77%. Participants vaccinated with R21/MM showed high titres of malaria-specific anti- Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered one year later.
Currently, there are no safety and immunogenicity data for the use of R21/MatrixM in Asian populations. This trial will generate the required data for the use of this vaccine in Asia. For integration with the current targeted malaria elimination (TME) activities, which provide mass drug administrations at months M0, M1, and M2, it would be most efficient and practical to provide the vaccine at the same intervals.
In summary: The investigators propose to conduct a safety and immunogenicity trial of R21/MatrixM in Thai adults. The major aims of this study are to 1) assess the safety and immunogenicity of R21/MatrixM in Thai adults 2) confirm that the co-administration of antimalarial drugs with the malaria vaccine R21/MatrixM does not reduce the immunogenicity of the vaccine and 3) assess the absorption and pharmacokinetics of antimalarial drugs piperaquine, and a single low dose of primaquine (SLDPQ) when co-administered with R21/MatrixM.
This is a randomized, open label, single centre, Phase 2 study. 120 healthy non-pregnant Thai adults, aged 18-55 years, inclusive, will be recruited.
Each participant will be randomized into one of the following study arms in a ratio of 5:5:2, as follows:
- R21/MatrixM + Dihydroartimisinin (DHA)-Piperaquine (PIP)+ primaquine (PQ) (Group 1, n=50) will receive R21/MatrixM + 3 doses DHA-PIP+PQ at Month 0, Month 1 and Month 2
- R21/MatrixM only (Group 2, n=50) will receive R21/MatrixM standard dose at Month 0, Month 1 and Month 2
- DHA-PIP+PQ only (Group 3, n=20) will receive 3 doses DHA-PIP+PQ at Month 0, Month 1 and Month 2
详细描述
This is a randomized, open label, single centre, Phase 2 study.
Screening and eligibility assessment (Screening visit) All potential volunteers will have a screening visit, which may take place up to 7 days prior to enrolment. Once informed consent is given, a screening number will be assigned in sequential order. Screening numbers will be issued consecutively (e.g. R21-001, R21-002, R21-003, ...)
Enrolment, baseline assessment, regimen allocation, and first vaccination (Month 0 / Day 0 visit; Baseline visit) All inclusion and exclusion criteria will be checked before enrolment in the study. Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for baseline P. falciparum testing, haemoglobin and biochemistry. Participants with parasitaemia or anaemia will be treated according to national guidelines. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-circumsporozoite antibody) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test.
Enrolment, baseline assessment, regimen allocation, and first vaccination (Month 0 / Day 0 visit; Baseline visit)
All inclusion and exclusion criteria will be checked before enrolment in the study. Physical examination will be performed. Any new medical issues or symptoms that have arisen will be assessed. Blood will be collected for baseline P. falciparum testing, haemoglobin and biochemistry. Blood will be collected and stored for measurement of antibodies against P. falciparum circumsporozoite (anti-circumsporozoite antibody) until shipment to the reference laboratory. Urine will be collected from women of child-bearing age for immediate pregnancy test.
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
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
R21/Matrix-M + DHA-PIP+PQ
The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine
干预措施: R21/Matrix-M vaccination (Biological)
R21/Matrix-M + DHA-PIP+PQ
The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine
干预措施: DHA-PIP (Drug)
R21/Matrix-M + DHA-PIP+PQ
The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine
干预措施: PQ (Drug)
R21/Matrix-M only
The R21/Matrix-M vaccine (IM injection) only
干预措施: R21/Matrix-M vaccination (Biological)
DHA-PIP+PQ only
Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine
干预措施: DHA-PIP (Drug)
DHA-PIP+PQ only
Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine
干预措施: PQ (Drug)
结局指标
主要结局
Occurrence of Unsolicited Adverse Events (AEs), According to the Medical Dictionary for Regulatory Activities (MedRA) Classification.
时间窗: From the date of the first vaccination to 28 days after the last vaccination (up to approximately 1 month)
Occurrence of Serious Adverse Events (SAEs), According to the MedRA Classification.
时间窗: During the whole study period, i.e. during a 6-month follow-up period from the receipt of first vaccination
Occurrence of Solicited Adverse Event Within 7 Days of Each Vaccination
时间窗: Within 7 days of each vaccination.
次要结局
- Number of Participants With Seroconversions in HBsAg(at study Month 6)
- For Arms 1 and 3, Piperaquine Levels Following the Administration of the Antimalarials With or Without Vaccine(Study month 2)
- Number of Participants With Seroconversions in C-Term(at study Month 6)
- Number of Participants With Seroconversions in NANP(at study Month 6)
- Number of Participants With Seroconversions in R21(at study Month 6)