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This is an open-label, multi-centre Phase I/IIa dose escalation blood-stage malaria CHMI trial to assess the safety, immunogenicity and efficacy of the candidate malaria vaccine RH5.1/AS01. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years.
Volunteers will be recruited and vaccinated at the CCVTM, Oxford; Guys and St Thomas' NIHR CRF, London; and the NIHR WTCRF, Southampton for the Phase Ia part of the trial, and at the CCVTM, Oxford and Guys and St Thomas' NIHR CRF, London for the Phase IIa stage.
This is a descriptive phase I trial to assess the safety and immunogenicity of the RH5.1/AS01 vaccine in healthy volunteers at different doses, and to establish whether the RH5.1/AS01 vaccine can demonstrate a reduced parasite multiplication rate in vaccinated subjects compared to infectivity controls in a blood-stage controlled human malaria infection model.
There will be 6 study groups across two phases of the trial, with a total of 66 - 78 volunteers.
Vaccination of groups will be sequential from Group 1 to Group 3. Group 3 and 4 can be recruited simultaneously. Volunteers will be able to choose which group they are allocated to.
The vaccination dose for Group 5 has been decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. They will undergo blood-stage CHMI 2 weeks after the final vaccination and will be followed up until approximately 6 months after the final vaccination.
Group 6 volunteers will be infectivity controls, so will not receive any vaccinations.
Volunteers will be recruited and undergo screening visits, vaccination and clinic visits post-vaccination at their local trial site. Procedures will be performed on the visit time points indicated in the schedule of attendances.. Additional procedures or laboratory tests may be performed, at the discretion of the Investigators.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1-Phase Ia | Active Comparator | The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. |
|
| Group 2- Phase Ia | Active Comparator | The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. |
|
| Group 3-Phase Ia | Active Comparator | Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). |
|
| Group 4-Phase Ia | Active Comparator | Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) |
|
| Group 5-Phase IIa | Active Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RH5.1/ ASO1 | Biological | The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of the RH5.1/AS01 Vaccine by Demonstrating a Reduced PMR in Vaccinated Subjects Compared to Infectivity Controls Against 3D7 Clone Parasites in a CHMI Model. | PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint for the Phase IIa stage of the trial, and comparison of the endpoint between the Groups 5 and 6 will constitute the primary analysis for efficacy. | Measured during CHMI |
| Safety of RH5.1/AS01 in Healthy Malaria-naïve Adults in the UK. | Solicited and unsolicited adverse events collected passively and actively for 28 days post each vaccination. Number of volunteers reporting any unsolicited AEs post-any vaccination, as reported to investigators or in electronic diaries. | 8 months |
| the in Vitro Growth Inhibition Activity (GIA) Against 3D7 Clone P. Falciparum Parasites of IgG Purified From the Serum of Vaccinees. | The specific endpoints for GIA in vitro will be assessed from a titration of the purified IgG in the assay. | 2 weeks post final vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| the Humoral Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens. | Antibody responses to the RH5.1 protein generated by vaccination | 2 weeks post final vaccination |
| the Cellular Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens. |
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Inclusion Criteria:
Additional Inclusion Criteria for Groups 5 - 6
Exclusion Criteria:
Additional exclusion criteria for groups 5 - 6
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guys and St Thomas' NIHR CRF | London | United Kingdom | ||||
| Nihr Wtcrf |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36072606 | Derived | Salkeld J, Themistocleous Y, Barrett JR, Mitton CH, Rawlinson TA, Payne RO, Hou MM, Khozoee B, Edwards NJ, Nielsen CM, Sandoval DM, Bach FA, Nahrendorf W, Ramon RL, Baker M, Ramos-Lopez F, Folegatti PM, Quinkert D, Ellis KJ, Poulton ID, Lawrie AM, Cho JS, Nugent FL, Spence PJ, Silk SE, Draper SJ, Minassian AM. Repeat controlled human malaria infection of healthy UK adults with blood-stage Plasmodium falciparum: Safety and parasite growth dynamics. Front Immunol. 2022 Aug 22;13:984323. doi: 10.3389/fimmu.2022.984323. eCollection 2022. | |
| 34337556 |
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Group 5 and 6 volunteers were invited to join the re-challenge study and formed Groups 7 and 8
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1-Phase Ia | The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| FG001 | Group 2- Phase Ia | The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| FG002 | Group 3-Phase Ia | Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| FG003 | Group 4-Phase Ia | Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| FG004 | Group 5-Phase IIa | The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| FG005 | Group 6-Phase IIa | Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations. |
| FG006 | Group 7-Phase IIa | Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| FG007 | Group 8 -Phase IIa | Group 8 are infectivity controls who were originally in Group 6. |
| FG008 | Group 9 -Phase IIa | Group 9 are new infectivity controls |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Initial Recruitment |
|
| ||||||||||||||||||
| Invitation for Additional Challenge |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 | The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. |
| BG001 | Group 2 |
| 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 | Efficacy of the RH5.1/AS01 Vaccine by Demonstrating a Reduced PMR in Vaccinated Subjects Compared to Infectivity Controls Against 3D7 Clone Parasites in a CHMI Model. | PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint for the Phase IIa stage of the trial, and comparison of the endpoint between the Groups 5 and 6 will constitute the primary analysis for efficacy. | Group 5 vs Group 6 and Group 7 vs Group 9 compared as vaccinees versus primary infectivity controls | Posted | Mean | Standard Deviation | Parisite multiplication rate (PMR) | Measured during CHMI |
|
Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7
Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever.
Note: mortality & serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
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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 | 3 doses of 2µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Angela Minassian | University of Oxford | 0044 01865611425 | angela.minassian@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 | Oct 10, 2018 | Jul 5, 2021 | 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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The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01).
|
| Group 6-Phase IIa | No Intervention | Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations. |
| Group 7-Phase IIa | Active Comparator | Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) |
|
| Group 8 -Phase IIa | No Intervention | Group 8 are infectivity controls who were originally in Group 6. |
| Group 9 -Phase IIa | No Intervention | Group 9 are new infectivity controls |
|
T cell responses to the RH5.1 protein generated by vaccination |
| 2 weeks post final vaccination |
| Immunological Readouts for Association With a Reduced Parasite Multiplication Rate. | Statistical correlation between anti-RH5 antibody responses induced by the RH5.1 vaccine and PMR. A non-linear regression curve for all samples combined is available in the trial manuscript ; data is not presented here. | 8 months |
| Southampton |
| United Kingdom |
| Derived |
| Willcox AC, Huber AS, Diouf A, Barrett JR, Silk SE, Pulido D, King LDW, Alanine DGW, Minassian AM, Diakite M, Draper SJ, Long CA, Miura K. Antibodies from malaria-exposed Malians generally interact additively or synergistically with human vaccine-induced RH5 antibodies. Cell Rep Med. 2021 Jun 21;2(7):100326. doi: 10.1016/j.xcrm.2021.100326. eCollection 2021 Jul 20. |
| 34223402 | Derived | Minassian AM, Silk SE, Barrett JR, Nielsen CM, Miura K, Diouf A, Loos C, Fallon JK, Michell AR, White MT, Edwards NJ, Poulton ID, Mitton CH, Payne RO, Marks M, Maxwell-Scott H, Querol-Rubiera A, Bisnauthsing K, Batra R, Ogrina T, Brendish NJ, Themistocleous Y, Rawlinson TA, Ellis KJ, Quinkert D, Baker M, Lopez Ramon R, Ramos Lopez F, Barfod L, Folegatti PM, Silman D, Datoo M, Taylor IJ, Jin J, Pulido D, Douglas AD, de Jongh WA, Smith R, Berrie E, Noe AR, Diggs CL, Soisson LA, Ashfield R, Faust SN, Goodman AL, Lawrie AM, Nugent FL, Alter G, Long CA, Draper SJ. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med. 2021 Jun 11;2(6):701-719.e19. doi: 10.1016/j.medj.2021.03.014. |
| 33763653 | Derived | Nielsen CM, Ogbe A, Pedroza-Pacheco I, Doeleman SE, Chen Y, Silk SE, Barrett JR, Elias SC, Miura K, Diouf A, Bardelli M, Dabbs RA, Barfod L, Long CA, Haynes BF, Payne RO, Minassian AM, Bradley T, Draper SJ, Borrow P. Protein/AS01B vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors. Cell Rep Med. 2021 Feb 22;2(3):100207. doi: 10.1016/j.xcrm.2021.100207. eCollection 2021 Mar 16. |
| Adverse Event |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses.
If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers.
RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum.
The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.
| BG002 | Group 3 | Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| BG003 | Group 4 | Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| BG004 | Group 5 | The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. Note, group 7 constitutes volunteers from groups 5 so is not presented separately |
| BG005 | Group 6 | Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations. Note, group 8 constitutes volunteers from groups 6 so is not presented separately |
| BG006 | Group 9 | Group 9 are new infectivity controls |
| BG007 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | Years |
|
| 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 |
|
| OG001 | Group 2- Phase Ia | The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| OG002 | Group 3-Phase Ia | Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| OG003 | Group 4-Phase Ia | Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| OG004 | Group 5-Phase IIa | The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| OG005 | Group 6-Phase IIa | Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations. |
| OG006 | Group 7-Phase IIa | Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. |
| OG007 | Group 8 -Phase IIa | Group 8 are infectivity controls who were originally in Group 6. |
| OG008 | Group 9 -Phase IIa | Group 9 are new infectivity controls |
|
|
| Primary | Safety of RH5.1/AS01 in Healthy Malaria-naïve Adults in the UK. | Solicited and unsolicited adverse events collected passively and actively for 28 days post each vaccination. Number of volunteers reporting any unsolicited AEs post-any vaccination, as reported to investigators or in electronic diaries. | Note, detailed adverse event data is outlined within the study publication. Groups 6, 8 and 9 were not assessed for adverse events as part of this objective as they did not receive the trial vaccine. This objective is assessing the safety of the vaccine itself and therefore is not applicable to these groups. | Posted | Count of Participants | Participants | 8 months |
|
|
|
| Primary | the in Vitro Growth Inhibition Activity (GIA) Against 3D7 Clone P. Falciparum Parasites of IgG Purified From the Serum of Vaccinees. | The specific endpoints for GIA in vitro will be assessed from a titration of the purified IgG in the assay. | GIA activity of 10mg/ml purified IgG was measured at 2 weeks following final vaccination (D70 for Groups 1, 2 & 4 and D196 for Group 3). Objective is not applicable for groups 5-9. | Posted | Median | Standard Deviation | percentage of growth inhibition | 2 weeks post final vaccination |
|
|
|
| Secondary | the Humoral Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens. | Antibody responses to the RH5.1 protein generated by vaccination | Anti-RH5_FL IgG (ug/mL) at 2 weeks post final vaccination in groups 1-4, Fig 1C. This objective is not applicable to groups 5-9 | Posted | Median | Standard Deviation | ug/mL | 2 weeks post final vaccination |
|
|
|
| Secondary | the Cellular Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens. | T cell responses to the RH5.1 protein generated by vaccination | RH5-specific T cell responses were assessed by ex-vivo IFN-γ ELISPOT in fresh PBMC following stimulation with either RH5.1 protein at 2 weeks post final vaccination in Groups 1-4. This objective is not applicable to groups 5-9. | Posted | Median | Standard Deviation | SFU per million PBMC | 2 weeks post final vaccination |
|
|
|
| Secondary | Immunological Readouts for Association With a Reduced Parasite Multiplication Rate. | Statistical correlation between anti-RH5 antibody responses induced by the RH5.1 vaccine and PMR. A non-linear regression curve for all samples combined is available in the trial manuscript ; data is not presented here. | Not Posted | 8 months | Participants |
| 12 |
| 0 |
| 12 |
| 9 |
| 12 |
| EG001 | Group 2 | 3 doses of 10µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56 | 0 | 12 | 0 | 12 | 11 | 12 |
| EG002 | Group 3 | 2 doses of 50µg RH5.1 in 0.5mL AS01 at days 0 and 28, followed by 10µg RH5.1 in 0.5mL AS01 at day 182 | 0 | 12 | 1 | 12 | 9 | 12 |
| EG003 | Group 4 | 3 doses of 50µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56 | 0 | 14 | 0 | 14 | 10 | 14 |
| EG004 | Group 5 | 3 doses of 10 µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56 | 0 | 17 | 1 | 17 | 14 | 17 |
| EG005 | Group 6 | Primary CHMI controls | 0 | 15 | 0 | 15 | 0 | 15 |
| EG006 | Group 7 | Group 5 participants receiving 1 further dose of 10 µg RH5.1 in 0.5 mL AS01 approximately 4 months after the last immunisation | 0 | 9 | 1 | 9 | 3 | 9 |
| EG007 | Group 8 | Secondary CHMI controls | 0 | 8 | 0 | 8 | 0 | 8 |
| EG008 | Group 9 | Primary CHMI controls | 0 | 6 | 0 | 6 | 0 | 6 |
| Tonsilectomy | Surgical and medical procedures | MedDRA 22.0 | Systematic Assessment |
|
| Pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 22.0 | Systematic Assessment |
|
| Headache | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Oropharyngeal pain | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Rhinitis | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Rhinorrhoea | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Local Reaction | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Insomnia | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Athralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
Not provided
Not provided
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| D000079426 |
| Vector Borne Diseases |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|