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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Active Comparator | 10µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. |
|
| Group 2 | Active Comparator | 50µg of R21 on days 0, 28, and 56. |
|
| Group 3 | Active Comparator | 50µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. |
|
| Group 4 | Active Comparator | 2µg of R21 mixed with 50µg of Matrix-M |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| R21 | Biological |
| ||
| Matrix-M1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Assessment of solicited AEs in the first 7 days post vaccination. |
| 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. | Unsolicited AEs to be assessed up to 28 days post vaccination. |
| 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. | 6 months |
| 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. | At Day 0 (baseline), day 7 and day 28 post vaccination |
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Inclusion Criteria:
The volunteer must satisfy all the following criteria to be eligible for the study:
Exclusion Criteria:
The volunteer may not enter the study if any of the following apply:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital | Oxford | Oxfordshire | OX3 7LE | United Kingdom | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39805302 | Derived | Venkatraman N, Tiono AB, Bowyer G, Bellamy DG, Stockdale LK, Powlson J, Collins KA, Coulibaly S, Datoo MS, Silman D, Ouedraogo A, Nebie I, Imoukhuede EB, Brod F, Folegatti P, Dickinson-Craig E, Jamieson S, Bougouma EC, Wright D, Diarra A, Bliss CM, Morter R, Glenn G, Fries LF, Reimer JM, Lovgren-Bengtsson K, Baker M, Poulton I, Moyle S, Berrie E, Green N, Mukhopadhyay E, Viebig NK, Angus B, Lawrie A, Roberts R, Gilbert SC, Lewis DJM, Sirima SB, Ewer KJ, Hill AVS. Evaluation of a novel malaria anti-sporozoite vaccine candidate, R21 in Matrix-M adjuvant, in the UK and Burkina Faso: two phase 1, first-in-human trials. Lancet Microbe. 2025 Mar;6(3):100868. doi: 10.1016/S2666-5247(24)00084-3. Epub 2025 Jan 10. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1 | 10µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. R21 Matrix-M1 |
| FG001 | Group 2 | 50µg of R21 on days 0, 28, and 56. R21 |
| FG002 | Group 3 | 50µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. R21 Matrix-M1 |
| FG003 | Group 4 | 2µg of R21 mixed with 50µg of Matrix-M R21 Matrix-M1 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 | 10µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. R21 Matrix-M1 |
| BG001 | Group 2 | 50µg of R21 on days 0, 28, and 56. R21 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Posted | Number | Number of Adverse Events per group | Assessment of solicited AEs in the first 7 days post vaccination. |
|
Solicited adverse events will be recorded daily for 7 days post-vaccination Unsolicited AEs of all severities will be recorded from receipt of vaccination through 28 days post-vaccination. After study Day 28, only SAEs or new chronic medical conditions that require ongoing medical management will be recorded through to the last study visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 | 10µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. R21 Matrix-M1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bartholin's cyst | Reproductive system and breast disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain | General disorders | Systematic Assessment | Vaccination 1 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Adrian V Hill, DPhil FRCP | University of Oxford | +44 1865 617610 | adrian.hill@ndm.ox.ac.uk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 11, 2016 | Jul 15, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| C577873 | R21 monoclonal antibody |
| C000625666 | Matrix-M |
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| Biological |
|
| NIHR Wellcome Trust Clinical Research Facility, Hammersmith Hospital |
| London |
| W12 0HS |
| United Kingdom |
| BG002 | Group 3 | 50µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. R21 Matrix-M1 |
| BG003 | Group 4 | 2µg of R21 mixed with 50µg of Matrix-M R21 Matrix-M1 |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Group 3 | 50µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. R21 Matrix-M1 |
| OG003 | Group 4 | 2µg of R21 mixed with 50µg of Matrix-M R21 Matrix-M1 |
|
|
| 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. | Posted | Number | participants | Unsolicited AEs to be assessed up to 28 days post vaccination. |
|
|
|
| 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. | There is no SAEs in groups 2 and 3 | Posted | Number | Number of Serious AEs | 6 months |
|
|
|
| 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. | Posted | Number | participants | At Day 0 (baseline), day 7 and day 28 post vaccination |
|
|
|
| 0 |
| 11 |
| 1 |
| 11 |
| 10 |
| 11 |
| EG001 | Group 2 | 50µg of R21 on days 0, 28, and 56. R21 | 0 | 4 | 0 | 4 | 3 | 4 |
| EG002 | Group 3 | 50µg of R21 mixed with 50µg of Matrix-M on days 0, 28, and 56. R21 Matrix-M1 | 0 | 10 | 0 | 10 | 9 | 10 |
| EG003 | Group 4 | 2µg of R21 mixed with 50µg of Matrix-M R21 Matrix-M1 | 0 | 6 | 1 | 6 | 3 | 6 |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment | Vaccination 1 |
|
| Redness | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 1 |
|
| Swelling | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 1 |
|
| Itch | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 1 |
|
| Warmth | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 1 |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Vaccination 1 |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Vaccination 1 |
|
| Feverishness | General disorders | Systematic Assessment | Vaccination 1 |
|
| Fatigue | General disorders | Systematic Assessment | Vaccination 1 |
|
| Nausea | General disorders | Systematic Assessment | Vaccination 1 |
|
| Malaise | General disorders | Systematic Assessment | Vaccination 1 |
|
| Pain | General disorders | Systematic Assessment | Vaccination 2 |
|
| Redness | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 2 |
|
| Swelling | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 2 |
|
| Itch | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 2 |
|
| Warmth | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 2 |
|
| Fever | General disorders | Systematic Assessment | Vaccination 2 |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Vaccination 2 |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Vaccination 2 |
|
| Feverishness | General disorders | Systematic Assessment | Vaccination 2 |
|
| Headache | General disorders | Systematic Assessment | Vaccination 2 |
|
| Fatigue | General disorders | Systematic Assessment | Vaccination 2 |
|
| Nausea | General disorders | Systematic Assessment | Vaccination 2 |
|
| Malaise | General disorders | Systematic Assessment | Vaccination 2 |
|
| Pain | General disorders | Systematic Assessment | Vaccination 3 |
|
| Redness | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 3 |
|
| Swelling | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 3 |
|
| Itch | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 3 |
|
| Warmth | Skin and subcutaneous tissue disorders | Systematic Assessment | Vaccination 3 |
|
| Feverishness | General disorders | Systematic Assessment | Vaccination 3 |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Vaccination 3 |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment | Vaccination 3 |
|
| Headache | General disorders | Systematic Assessment | Vaccination 3 |
|
| Fatigue | General disorders | Systematic Assessment | Vaccination 3 |
|
| Nausea | General disorders | Systematic Assessment | Vaccination 3 |
|
| Malaise | General disorders | Systematic Assessment | Vaccination 3 |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment | Vaccination 1 |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment | Vaccination 2 |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment | Vaccination 3 |
|
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| D000079426 |
| Vector Borne Diseases |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|