A Phase II Clinical Study to Assess the Safety, Immunogenicity, and Efficacy of Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvRII/Matrix-M in Healthy Thai Adults Living in Thailand
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- solicited systemic adverse event
研究概览
简要总结
This project is the third part of a 5-year research program entitled "Malaria Infection Studies in Thailand (MIST)" and known as MIST3. MIST3's primary objectives are to assess the safety of the PvRII/Matrix-M vaccine candidate in healthy adult Thai volunteers and to establish whether the PvRII/Matrix-M vaccine can demonstrate a reduced parasite multiplication rate in vaccinated volunteers compared to a controlled group (placebo vaccine) in a blood-stage controlled human malaria infection model. This study will recruit up to 36 eligible healthy volunteers aged 20-55 in Thailand at the Faculty of Tropical Medicine, Mahidol University. Eighteen volunteers will receive three doses of the PvRII/Matrix-M candidate vaccine, and 18 volunteers will receive three doses of the placebo vaccine. Safety and immunogenicity will be evaluated after each dose as per protocol. Approximately four weeks after receiving the third vaccination, 24 volunteers will undergo blood-stage CHMI with Plasmodium vivax. The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases and treated according to the Research Proposal Submission Form.
This study is funded by the UK Wellcome Trust. The grant reference number are Oxford/MORU: 212336/Z/18/Z and 212336/Z/18/A, and Mahidol University: 212336/A/18/Z and 212336/A/18/A
详细描述
Summary of trial design: Phase II, double-blinded, randomized controlled trial with CHMI, designed to assess the safety, immunogenicity, and protective efficacy of PvRII/Matrix-M vaccine.
Overview: This is a randomized controlled single-centre Phase II P. vivax blood-stage CHMI trial to assess the safety, immunogenicity, and efficacy of the candidate malaria vaccine PvRII/Matrix-M.
Healthy Thai adults aged between 20 and 55 years will be recruited and randomized at the Faculty of Tropical Medicine, Mahidol University in Bangkok.
Vaccination group: Up to 18 healthy adults aged between 20 and 55 years will be recruited. These volunteers will receive three doses of the PvRII/Matrix-M vaccine intramuscularly at months 0, 1, and 6.
Approximately three to four weeks post-boost (3rd vaccination), 12 volunteers will undergo P. vivax blood-stage CHMI, induced by injection of P. vivax infected erythrocytes.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
double-blinded placebo
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Thai adults aged 20 to 55 years
- •Minimum educational level of high school or equivalent
- •Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
- •Women only: Must practice continuous effective contraception for the duration of the study period until 3 months post-challenge.
- •Agreement to refrain from blood donation during the study and for 1 year after the initiation of antimalarial treatment.
- •Willing to be admitted to the Hospital for Tropical Diseases for clinical monitoring as required by the protocol until antimalarial treatment is completed and their symptoms are settling, willing to take a curative antimalarial treatment following CHMI, and willing to reside in Bangkok and its vicinity for 2 months after malarial treatment initiation.
- •Able to read and write in Thai.
- •Provide written informed consent to participate in the trial
- •Answer all questions on the informed consent quiz correctly
- •Completed COVID-19 vaccination with 2 doses of any WHO-approved vaccine
排除标准
- •Positive malaria qPCR OR malaria film prior to vaccination and challenge
- •Presence of any medical condition (either physical or psychological) that, in the judgment of the investigator, would place the participant at undue risk (including the history of clinically significant contact dermatitis) or interfere with the results of the study (e.g., underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
- •Presence of chronic disease or chronic use of medication
- •Prior receipt of other investigational vaccine which is likely to impact the interpretation of the trial data as assessed by the Investigator.
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, history of splenectomy, recurrent severe infections, and chronic infection
- •Immunosuppressant medication within the past 6 months preceding enrolment (D0) or plan to use during the study (inhaled and topical steroids are allowed)
- •History of allergic disease or reactions likely to be exacerbated by malaria infection
- •Female participant who is pregnant as evidenced by positive beta-human chorionic gonadotropin (β-HCG) test, or who is lactating or planning pregnancy during the course of the study.
- •Contraindications to the use of antimalarial treatment (e.g., chloroquine, atovaquone/proguanil, or dihydroartemisinin/piperaquine)
- •Use of medications known to have potentially clinically significant interaction with the antimalarial drugs that will be used in this study (chloroquine, atovaquone/proguanil, or dihydroartemisinin/piperaquine)
- •History of cardiac arrhythmia, including clinically relevant bradycardia or Known existing positive family history in both 1st AND 2nd-degree relatives < 50 years old for cardiac disease
- •Family history of congenital QT prolongation or sudden death
- •Any clinical condition, including using medications known to prolong the QT interval or screening electrocardiogram (ECG), demonstrates a QTc interval ≥ 450 ms.
- •Suspected or known history of alcohol abuse or history of drug abuse.
- •Concurrently participating in another clinical study, at any time during the study period
- •Positive hepatitis B surface antigen or seropositive for hepatitis C virus, or HIV
- •Finding on safety laboratory values as defined below:
- •Abnormal ALT [>upper normal range]
- •Abnormal serum creatinine [>upper normal range]
- •Clinically significant abnormalities in corrected calcium and magnesium blood levels
- •Haemoglobin < 11 g/dL
- •Blood group Rhesus negative
- •Blood incompatibility to the inoculum
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
- •Any history of anaphylaxis in reaction to vaccinations
- •Vaccination and re-vaccination exclusion criteria
- •1. Acute disease at the time of vaccination. (acute disease is defined as the presence of a moderate or severe illness with or without fever).
- •The following adverse events associated with vaccine immunisation constitute absolute contraindications to further vaccine administration. If any of these events occur during the study, the participant must be withdrawn and followed until the resolution of the event, as with any adverse event:
- •Anaphylactic reaction following administration of the vaccine
- •Exclusion criteria on the day of CHMI
- •The following constitute absolute contraindications to CHMI:
- •Acute disease, defined as a moderate or severe illness with or without fever
- •Use of systemic antibiotics with known antimalarial activity in the 30 days before challenge (e.g., trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, and azithromycin)
研究组 & 干预措施
Malaria Vaccine
PvRII/Matrix-M month 0, month 1, month 6
干预措施: Malaria Vaccine (Biological)
control
HBV vaccine month 0, month 1, month 6
干预措施: HBV vaccine (Biological)
结局指标
主要结局
solicited systemic adverse event
时间窗: 7 days following each vaccination
occurrence of solicited systemic reactogenicity signs and symptoms
unsolicited adverse events
时间窗: 28 days following each vaccination
Occurrence of unsolicited adverse events
safety laboratory measures
时间窗: 28 days following each vaccination
Number of participants with abnormal laboratory test results
solicited local adverse event
时间窗: 7 days following each vaccination
occurrence of solicited local reactogenicity signs and symptoms
serious adverse events
时间窗: through study completion, an average of 1 year
Occurrence of serious adverse events during the whole study duration
feasibility of primary P. vivax blood-stage CHMI
时间窗: within 21 days following CHMI
successful infection (development of detectable persistent parasitaemia by thick blood film +/- clinical symptoms)
次要结局
未报告次要终点