MalariaPhase 1/2NCT02927145
A Challenge Study to Assess the Safety, Immunogenicity and Efficacy of a Malaria Vaccine Candidate
A Phase 1/2 study testing RH5.1/ ASO1 in people with Malaria, run by University of Oxford at 2 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- RH5.1/ ASO1
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 17 Oct 2016to 27 Jun 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18 to 45 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 (GP).
- 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, and on the day prior to blood-stage CHMI, and prior to the start of antimalarial treatment for Group 5 and 6 volunteers.
- Agreement to refrain from blood donation during the course of the study.
- Provide written informed consent.
Show all 11Show fewer
- Additional Inclusion Criteria for Groups 5 - 6
- Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines.
- Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment.
- Willingness to take a curative anti-malaria regimen following CHMI.
- Answer all questions on the informed consent questionnaire correctly.
Who cannot join
- 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.
- Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe.
- 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 during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone 20 mg/day (for adult subjects), or equivalent. Inhaled and topical steroids are allowed.
- Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
Show all 34Show fewer
- Chronic use of antibiotics with antimalarial effects (e.g. tetracyclines for dermatologic patients, sulfa for recurrent urinary tract infections, etc.).
- History of malaria chemoprophylaxis within 60 days prior to vaccination.
- 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.
- Additional exclusion criteria for groups 5 - 6
- Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
- History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
- Use of medications known to cause prolongation of the QT interval AND existing contraindication to the use of Malarone.
- Use of medications known to have a potentially clinically significant interaction with Riamet AND Malarone.
- Contraindications to the use of all three proposed anti-malarial medications; Riamet, Malarone and Chloroquine.
- Any clinical condition known to prolong the QT interval.
- Family history of congenital QT prolongation or sudden death.
- Positive family history in 1st and 2nd degree relatives < 50 years old for cardiac disease.
- History of cardiac arrhythmia, including clinically relevant bradycardia.
- Volunteer unable to be closely followed for social, geographic or psychological reasons.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Guys and St Thomas' NIHR CRF
London
Nihr Wtcrf
Southampton
About this study
Official title: A Phase I/IIa Clinical Trial to Assess the Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Falciparum Malaria Vaccine Candidate RH5.1/AS01
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.
Read the detailed description
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.
- Conditions
- Malaria
- Being tested
- RH5.1/ ASO1
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RH5.1/ ASO1Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: RH5.1/ ASO1 |
| 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. Receives: Biological: RH5.1/ ASO1 |
| 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). Receives: Biological: RH5.1/ ASO1 |
| 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) Receives: Biological: RH5.1/ ASO1 |
| Group 5-Phase IIa | Active comparator | 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). Receives: Biological: RH5.1/ ASO1 |
| 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) Receives: Biological: RH5.1/ ASO1 |
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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.
Measured: 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.
Measured: 2 weeks post final vaccination
Secondary outcomes (3)
the Humoral Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens.
Antibody responses to the RH5.1 protein generated by vaccination
Measured: 2 weeks post final vaccination
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
Measured: 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.
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2016 (estimated)
- Study start17 Oct 2016
- Primary completion27 Jun 2019
- Study completion27 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02927145
- Sponsor's protocol ID
- VAC063
- Status last verified
- Aug 2019
- First submitted
- 5 Sep 2016
- Last updated
- 18 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 36072606Willcox 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.
PubMed 34337556Minassian 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.
PubMed 34223402Nielsen 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.
PubMed 33763653
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Clinical Trial to Assess the Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Falciparum Malaria Vaccine Candidate RH5.1/AS01
- ClinicalTrials.gov ID
- NCT02927145
- Acronym / sponsor ID
- VAC063
- Conditions
- Malaria
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 17 Oct 2016 (actual)
- Primary completion
- 27 Jun 2019 (actual)
- Study completion
- 27 Jun 2019 (actual)
- First posted
- 6 Oct 2016 (estimated)
- Results
- Posted 18 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Group 1-Phase Ia | Active comparator | Biological: RH5.1/ ASO1The 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 | Biological: RH5.1/ ASO1The 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 | Biological: RH5.1/ ASO1Group 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 | Biological: RH5.1/ ASO1Group 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 | Biological: RH5.1/ ASO1The 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 | Biological: RH5.1/ ASO1Group 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy adults aged 18 to 45 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 (GP).
- 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, and on the day prior to blood-stage CHMI, and prior to the start of antimalarial treatment for Group 5 and 6 volunteers.
- Agreement to refrain from blood donation during the course of the study.
Key exclusion criteria (34 listed)
- 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.
- Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe.
- 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 during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone 20 mg/day (for adult subjects), or equivalent. Inhaled and topical steroids are allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RH5.1/ ASO1The 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. | Biological | Group 1-Phase Ia, Group 2- Phase Ia, Group 3-Phase Ia, Group 4-Phase Ia, Group 5-Phase IIa, Group 7-Phase IIa |
Primary outcome
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.
Time frame: Measured during CHMI
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.
Safety of RH5.1/AS01 in Healthy Malaria-naïve Adults in the UK.
Time frame: 8 months
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.
the in Vitro Growth Inhibition Activity (GIA) Against 3D7 Clone P. Falciparum Parasites of IgG Purified From the Serum of Vaccinees.
Time frame: 2 weeks post final vaccination
The specific endpoints for GIA in vitro will be assessed from a titration of the purified IgG in the assay.
3 secondary outcomes
the Humoral Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens.
Time frame: 2 weeks post final vaccination
the Cellular Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens.
Time frame: 2 weeks post final vaccination
Immunological Readouts for Association With a Reduced Parasite Multiplication Rate.
Time frame: 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36072606Salkeld 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.
- Derived from this study: PubMed 34337556Willcox 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.
- Derived from this study: PubMed 34223402Minassian 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.
- Derived from this study: PubMed 33763653Nielsen 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.
- Individual participant dataSharing planned: Undecided
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RH5.1/ ASO1 in people with Malaria, run by University of Oxford at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Measured during CHMI). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02927145, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2022.