A Phase Ib Clinical Trial to Assess the Safety and Immunogenicity of the Blood-stage Plasmodium Falciparum Malaria Vaccine Candidate RH5.1/Matrix-M in Healthy Adults and Infants in Tanzania
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Safety of RH5.1-Matrix-M given in 3 doses in healthy Tanzanian adults and children naturally exposed to malaria as assessed by the occurrence of serious adverse events.
研究概览
简要总结
This is an age de-escalation, dose-escalation open label randomised trial studying the safety and immunogenicity of RH5.1/Matrix-M, administered intramuscularly in healthy adults, young children and infants in Tanzania
详细描述
A total of 60 participants will be enrolled consisting of healthy adults (18-45 years) and infants (5-17 months) residing in Bagamoyo district, Tanzania. Participants will be recruited from areas of low malaria transmission in Bagamoyo town and areas of high malaria transmission within Bagamoyo district. All participants will be followed for 2-2.5years after the first vaccination with RH5.1/Matrix-M vaccination. The duration of the entire study will be 2-2.5years per participant from the time of first vaccination.
The trial is funded by EDCTP (reference: RIA2016V-1649 MMVC).
The paper containing this trial's results is available at: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00312-8/fulltext
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
- None
入排标准
- 年龄范围
- 5 Months 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group 1: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent.
- •Group 1 (Female only participants): Must be non-pregnant (as demonstrated by a negative urine pregnancy test), and practice continuous effective contraception* for the duration of the study. (Female volunteers are required to use an effective form of contraception during the course of the study as this is a Phase I, study and there is currently no information about the effect of this vaccine on a foetus. Acceptable forms of contraception for female volunteers include:
- •Established use of oral, injected or implanted hormonal methods of contraception.
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- •Total abdominal hysterectomy.
- •Groups 2a, 2b, 2c & 2d: Healthy male or female infants aged 5-17 months at the time of enrolment with signed consent obtained from parents or guardians.
- •Planned long-term (at least 24 months from the date of recruitment) or permanent residence in the study area.
- •Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or infants with Z-score of weight- for-age within ±2SD.
排除标准
- •Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
- •Clinically significant history of skin disorder (psoriasis, contact dermatitis etc.), allergy, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease and neurological illness as judged by the PI or other delegated individual.
- •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 cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
- •Weight for age z-scores below 2 standard deviations of normal for age.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, Kathon, neomycin, betapropiolactone.
- •Any history of anaphylaxis in relation to vaccination.
- •Clinically significant laboratory abnormality as judged by the PI or other delegated individual.
- •Blood transfusion within one month of enrolment.
- •History of vaccination with previous experimental malaria vaccines.
- •Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
- •Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
- •Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG).
- •Any other finding which in the opinion of the PI or other delegated individual would increase the risk of an adverse outcome from participation in the trial.
- •Likelihood of travel away from the study area.
- •Positive malaria by blood smear at screening.
- •Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
- •Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
- •Any other significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
研究组 & 干预措施
Group 1A
Volunteers (aged 18-45 years) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 2
干预措施: RH5.1/Matrix-M (Biological)
Group 1B
Volunteers (aged 18-45 years) of low malaria exposure status will receive 2 doses of 50µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /50µg Matrix-M at month 6.
干预措施: RH5.1/Matrix-M (Biological)
Group 2A
Volunteers (aged 5-17 months) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 2.
干预措施: RH5.1/Matrix-M (Biological)
Group 2B
Volunteers (aged 5-17 months) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 6.
干预措施: RH5.1/Matrix-M (Biological)
Group 2C
Volunteers (aged 5-17 months) of low malaria exposure status will receive 2 doses of 50µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /50µg Matrix-M at month 6.
干预措施: RH5.1/Matrix-M (Biological)
Group 2D
Volunteers (aged 5-17 months) of high malaria exposure status will receive 2 doses of 50µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /50µg Matrix-M at month 6.
干预措施: RH5.1/Matrix-M (Biological)
结局指标
主要结局
Safety of RH5.1-Matrix-M given in 3 doses in healthy Tanzanian adults and children naturally exposed to malaria as assessed by the occurrence of serious adverse events.
时间窗: Assessment of SAEs until the end of the study (approx 2 years)
Occurrence of serious adverse events throughout the study period.
Safety of RH5.1-Matrix-M given in 3 doses in healthy Tanzanian adults and children naturally exposed to malaria as assessed by the occurrence of solicited symptoms.
时间窗: Assessment of solicited symptoms in the first 7 days post vaccination
Occurrence of solicited symptoms after each vaccination during a 7-day surveillance period.
Safety of RH5.1-Matrix-M given in 3 doses in healthy Tanzanian adults and children naturally exposed to malaria as assessed by the occurrence of unsolicited symptoms.
时间窗: Assessment of unsolicited symptoms in the first 30 days post vaccination
Occurrence of unsolicited symptoms after each vaccination during a 28-day surveillance period (day of vaccination and 28 subsequent days).
次要结局
- Anti-RH5 antibody concentration by ELISA(Through study completion (approx 2 years))
- Growth inhibition activity of IgG from vaccinees on a panel of P. falciparum parasites(Through study completion (approx 2 years))
- Avidity of anti-RH5 antibodies by ELISA and/or other assays (to be defined)(Through study completion (approx 2 years))
- Cellular immune responses to the RH5 by ELISpot assay and/or Flow cytommetry(Through study completion (approx 2 years))