Malaria
Conditions
Brief summary
This is a clinical trial in which healthy volunteers will be administered one or two experimental malaria vaccines. The vaccine R21 will either be administered alone or in combination with the adjuvant vaccine Matrix-M1. All vaccinations will be administered intramuscularly. Each volunteer will receive three vaccinations in total. There are three different vaccine schedules: Group 1 will receive 10µg of R21 mixed with 50µg of Matrix-M1 on days 0, 28, and 56. Group 2 will receive 50µg of R21 on days 0, 28, and 56. . Group 3 will receive 50µg of R21 mixed with 50µg of Matrix-M1 on days 0, 28, and 56. The study will assess the safety of the vaccines, and the immune responses to the vaccinations. Immune responses are measured by tests on blood samples. Healthy adult volunteers will be recruited in Oxford and London, England.
Sponsors
University of Oxford
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
The volunteer must satisfy all the following criteria to be eligible for the study: * Healthy adults aged 18 to 50 years * Able and willing (in the Investigator's opinion) to comply with all study requirements * Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner * For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination * Agreement to refrain from blood donation during the course of the study * Provide written informed consent
Exclusion criteria
The volunteer may not enter the study if any of the following apply: * Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period * Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. * Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate * 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 allergic disease or reactions likely to be exacerbated by any component of the vaccine * Any history of anaphylaxis in relation to vaccination * Pregnancy, lactation or willingness/intention to become pregnant during the study * History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) * History of serious psychiatric condition likely to affect participation in the study * Any other serious chronic illness requiring hospital specialist supervision * Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week * Suspected or known injecting drug abuse in the 5 years preceding enrolment * Seropositive for hepatitis B surface antigen (HBsAg) * Seropositive for hepatitis C virus (antibodies to HCV) * History of clinical malaria (any species) * Travel to a malaria endemic region during the study period or within the previous six months * Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis * Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data * Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Administration of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events. | Assessment of solicited AEs in the first 7 days post vaccination. | Occurrence of solicited local and systemic adverse events (i.e: pain, redness, swelling and pruritus at injection site and temperature, feverishness, myalgia, arthralgia, malaise, headache and nausea). |
| Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Unsolicited Adverse Events. | Unsolicited AEs to be assessed up to 28 days post vaccination. | Occurrence of unsolicited local and systemic adverse events. |
| Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Serious Adverse Events. | 6 months | Occurrence of serious adverse events collected from enrolment until the end of the follow-up period. |
| Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Laboratory Adverse Events. | At Day 0 (baseline), day 7 and day 28 post vaccination | Occurrence of laboratory adverse events defined as clinically significant changes from baseline. Haematology (Full Blood Count) and Biochemistry (Kidney and Liver Function Tests) will be assessed. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 10µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56.
R21
Matrix-M1 | 11 |
| Group 2 50µg of R21 on days 0, 28, and 56.
R21 | 4 |
| Group 3 50µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56.
R21
Matrix-M1 | 10 |
| Group 4 2µg of R21 mixed with 50µg of Matrix-M
R21
Matrix-M1 | 6 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Group 2 | Group 3 | Group 4 | Group 1 |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 4 Participants | 10 Participants | 6 Participants | 11 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — | — |
| Region of Enrollment United Kingdom | 31 participants | 4 participants | 10 participants | 6 participants | 11 participants |
| Sex: Female, Male Female | 16 Participants | 2 Participants | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 15 Participants | 2 Participants | 5 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 4 | 0 / 10 | 0 / 6 |
| other Total, other adverse events | 10 / 11 | 3 / 4 | 9 / 10 | 3 / 6 |
| serious Total, serious adverse events | 1 / 11 | 0 / 4 | 0 / 10 | 1 / 6 |
Outcome results
Primary
Safety and Tolerability of Administration of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events.
Occurrence of solicited local and systemic adverse events (i.e: pain, redness, swelling and pruritus at injection site and temperature, feverishness, myalgia, arthralgia, malaise, headache and nausea).
Time frame: Assessment of solicited AEs in the first 7 days post vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Safety and Tolerability of Administration of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events. | 103 Number of Adverse Events per group |
| Group 2 | Safety and Tolerability of Administration of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events. | 21 Number of Adverse Events per group |
| Group 3 | Safety and Tolerability of Administration of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events. | 94 Number of Adverse Events per group |
| Group 4 | Safety and Tolerability of Administration of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events. | 21 Number of Adverse Events per group |
Primary
Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Laboratory Adverse Events.
Occurrence of laboratory adverse events defined as clinically significant changes from baseline. Haematology (Full Blood Count) and Biochemistry (Kidney and Liver Function Tests) will be assessed.
Time frame: At Day 0 (baseline), day 7 and day 28 post vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Laboratory Adverse Events. | 11 participants |
| Group 2 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Laboratory Adverse Events. | 4 participants |
| Group 3 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Laboratory Adverse Events. | 10 participants |
| Group 4 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Laboratory Adverse Events. | 6 participants |
Primary
Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Serious Adverse Events.
Occurrence of serious adverse events collected from enrolment until the end of the follow-up period.
Time frame: 6 months
Population: There is no SAEs in groups 2 and 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Serious Adverse Events. | 1 Number of Serious AEs |
| Group 2 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Serious Adverse Events. | 0 Number of Serious AEs |
| Group 3 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Serious Adverse Events. | 0 Number of Serious AEs |
| Group 4 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Serious Adverse Events. | 1 Number of Serious AEs |
Primary
Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Unsolicited Adverse Events.
Occurrence of unsolicited local and systemic adverse events.
Time frame: Unsolicited AEs to be assessed up to 28 days post vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Unsolicited Adverse Events. | 11 participants |
| Group 2 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Unsolicited Adverse Events. | 4 participants |
| Group 3 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Unsolicited Adverse Events. | 10 participants |
| Group 4 | Safety and Tolerability of R21 With and Without the Adjuvant Matrix-M1 Assessed by the Occurrence of Unsolicited Adverse Events. | 6 participants |