A Challenge Study to Assess the Safety, Immunogenicity and Efficacy of a Malaria Vaccine Candidate
NCT ID: NCT02927145
Last Updated: 2022-02-18
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
88 participants
INTERVENTIONAL
2016-10-17
2019-06-27
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Study to Assess the Safety and Immunogenicity of a Malaria Vaccine Candidate, R21, Administered With AS01B
NCT02600975
A Phase Ia Clinical Trial to Assess the Safety and Immunogenicity of the Blood-stage Malaria Candidate Vaccines RH5.1 in Matrix-M and R78C in Matrix-M in Healthy UK Adults
NCT05385471
A Phase Ia Clinical Trial to Assess the Safety and Immunogenicity of New Plasmodium Falciparum Malaria Vaccine Candidates ChAd63 RH5 Alone and With MVA RH5
NCT02181088
A Study to Evaluate the Efficacy, Immunogenicity and Safety in a Sporozoite Challenge Model of a Fractional Booster Dose of GSK Biologicals' Candidate Malaria Vaccine Administered to Previously Vaccinated Healthy Malaria-naïve Adults
NCT03824236
A Study to Compare Two Dosing Regimens for a New Malaria Vaccine
NCT06141057
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
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.
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.
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.
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.
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.
No interventions assigned to this group
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.
Group 8 -Phase IIa
Group 8 are infectivity controls who were originally in Group 6.
No interventions assigned to this group
Group 9 -Phase IIa
Group 9 are new infectivity controls
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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.
* 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.
Exclusion Criteria
* 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).
* 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.
* 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.
18 Years
45 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Oxford
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Guys and St Thomas' NIHR CRF
London, , United Kingdom
Nihr Wtcrf
Southampton, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
VAC063
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.