VAC 072-An efficacy study of R21/MM in different dose schedules
Research type
Research Study
Full title
A Phase I/IIa Sporozoite Challenge Study to assess the safety, immunogenicity and protective efficacy of adjuvanted R21, administered in different dose schedules in healthy UK volunteers.
IRAS ID
254572
Contact name
Adrian Hill
Contact email
Sponsor organisation
University of Oxford
Eudract number
2018-004391-34
ISRCTN Number
ISRCTN00000000
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
VAC072 REC Reference, 18/SC/0679
Duration of Study in the UK
1 years, 7 months, 2 days
Research summary
Summary of Research
This is a clinical trial in which healthy volunteers will be administered experimental malaria vaccines. Five groups of volunteers will receive vaccination with the novel malaria vaccine candidate, R21 in combination with the vaccine adjuvant, Matrix M. In Group 1 and 3, vaccines will be delivered at 4 week intervals (ie. At 0, 4 & 8 weeks). In Group 2, 4 & 5, vaccines will be delivered initially at a 4 week interval but the last interval will be 24 weeks to assess if a staggered dose affects the immune response. In Groups 4 & 5, this third dose will also be a fractional dose. Fractional, delayed vaccine dosing has been shown to improve efficacy with RTS,S.The study will assess the safety of the vaccinations, and the immune responses to vaccination. Immune responses are measured by tests on blood samples. Volunteers will be infected with malaria by mosquito bites, 12 weeks after the first vaccination in Group 3 and 32 weeks after the first vaccination in Group 2. In addition, a group of volunteers not receiving vaccines will also be infected with malaria by the same method. These infection experiments will be used to assess vaccine efficacy: how well the vaccines act to prevent malaria disease. Groups 1, 4 & 5, will not be given malaria infection.
R21 is a protein particle, which is produced by combining a protein from Hepatitis B with the circumsporozoite protein (CSP) of the malaria parasite. This is not a live vaccine and so there is no chance of catching malaria.
Healthy volunteers will be recruited in England across four research sites: in Oxford, London, and Southampton.
Summary of results
THANK YOU!
The University of Oxford and the study team thank all the participants for taking part in this clinical study. You helped us, the researchers, learn more about the malaria vaccine candidate, R21/Matrix-M.
We would like to share the results of this study with you. We hope this summary of the study results helps you to understand, and feel proud of, your key role in medical research. If you have questions about the results, please contact the study team.Study Full Title: A Phase I/IIa Sporozoite Challenge Study to assess the safety, immunogenicity and protective efficacy of adjuvanted R21, administered in different dose schedules in healthy UK volunteers.
Who carried out the research?
The study was carried out by researchers at the University of Oxford.
What public involvement there was in the study?
77 healthy volunteers were recruited for the study and either received 3 vaccinations, 4 vaccinations or no vaccines. 44 volunteers were included in the malaria challenge part of the study and 9 volunteers took part in a second malaria challenge.
Where and when the study took place?
The study took place in the UK at four sites: Oxford, London (2 sites) and Southampton. All participants were followed up in Oxford for the duration of the malaria challenge follow up period.
Why was the research needed?
Malaria kills large numbers of people every year. A highly effective vaccine could save many lives.
What were the main questions studied?
The study was performed to check whether a course of R21/Matrix-M malaria vaccines was safe, produced immune responses against malaria, and could protect people against deliberate infection with malaria.
Who participated in the study?
Healthy volunteers aged 18 to 45 took part. All volunteers had a medical assessment to check they met the study requirements before taking part and did a questionnaire to make sure they fully understood what was involved when being infected with malaria. Volunteers were recruited across Oxford, London and Southampton.What treatments or interventions did the participants take/receive?
There were 5 different vaccine groups that received different doses and schedules of the R21/Matrix-M vaccine. Following this, in some groups, volunteers were infected with malaria to assess how well the vaccines protected against malaria.What medical problems (adverse reactions) did the participants have?
Post vaccination symptoms were mostly reported in the 72-hour period following vaccinations. Pain at the vaccination site was the most common adverse event reported and also some flu-like symptoms. Most symptoms reported were mild in nature.What happened during the study?
Participants were recruited to receive three vaccinations with an investigational malaria vaccine over 2 or 6 months and to attend follow up visits to collect blood samples. They also completed online symptom diaries to collect safety data. Half of the volunteers were subsequently exposed to the malaria parasites by allowing malaria infected mosquitos to bite their arms in controlled conditions. A control group was also recruited, who did not receive any vaccine. Participants were intensively followed up after malaria exposure to see if they developed malaria. A subset of volunteers who were protected against malaria following this initial challenge agreed to have a booster vaccination. Following this, they were exposed to malaria again and followed up intensively again to see if they developed malaria.What were the results of the study?
The vaccines were well-tolerated and generated good immune responses, in particular high levels of antibodies, to the malaria parasite. Furthermore, it showed evidence that the vaccine regimes tested can prevent malaria infection. There was a significant difference in the number of individuals developing malaria in the control group compared with the vaccine groups, with fewer cases in the vaccinees. Post-vaccination side effects were common although these were mostly graded as mild and resolved quickly.
How has this study helped patients and researchers?
This study has shown that R21/Matrix-M malaria vaccine may prevent malaria infection. This is promising for the future in helping fight against malaria as only one vaccine for preventing malaria has been approved by the WHO to date.
Details of any further research planned
The R21/Matrix-M malaria vaccine is currently in large clinical trials in sub-Saharan Africa assessing if it protects against malaria in children in malaria endemic areas with the aim of licensing this vaccine for widespread use in malaria endemic areas and potentially also for travellers.
Where can I learn more about this study?
The full study results will be published in a scientific journal shortly.REC name
South Central - Oxford A Research Ethics Committee
REC reference
18/SC/0679
Date of REC Opinion
19 Feb 2019
REC opinion
Further Information Favourable Opinion