Plasmodium falciparum malaria
Conditions
Interventions
Product Name: RH5.1
Pharmaceutical Form: Solution for injection
Product Name: AS01B
Pharmaceutical Form: Solution for injection
Sponsors
University of Oxford, CTRG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The volunteer must satisfy all the following criteria to be eligible for the study: •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 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 5-9 volunteers. •Agreement to refrain from blood donation during the course of the study. •Provide written informed consent. Additional Inclusion Criteria for Groups 5 - 9 •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. •For Groups 7-8: completion of primary challenge, curative antimalarials and follow-up (up until at least the C+28 visit) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: The volunteer may not enter the study if any of the following apply: •Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. •Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. For Group 7 volunteers undergoing re-challenge, this exclusion criterion does not extend to the RH5.1/AS01B vaccine previously received. •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. •History of splenectomy. •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) at screening (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study). •History of clinical malaria (any species). (Not applicable to Groups 7 and 8). •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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety of the RH5.1/AS01 vaccine in healthy volunteers at different doses. 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. ; Secondary Objective: To assess the humoral and cellular immunogenicity of RH5.1/AS01 when administered to healthy volunteers at different doses. To assess immunological readouts for association with a reduced parasite multiplication rate. To assess the durability of any reduction in parasite multiplication rate (PMR) in vaccinated Group 5 subjects by subjecting them to a re-challenge with 3D7 clone parasites approximately 4 months after the primary challenge (Group 7), and comparing the PMR with 1) that of previously challenged Group 6 controls receiving a second challenge (Group 8); and 2) that of newly recruited malaria-naïve controls (Group 9) receiving a primary challenge.assess immunological readouts for association with a reduced parasite multiplication rate. This is using the same Phase IIa blood-stage controlled human malaria infection (CHMI) model. ; Primary end point(s): The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The specific endpoints for GIA in vitro will be assessed from a titration of the purified IgG in the assay. 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. ; Timepoint(s) of evaluation of this end point: Volunteers will complete diary cards for 28 days after each vaccination and will be seen 1, 7, 14 and 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the humoral and cellular immunogenicity of RH5.1/AS01 using different vaccine doses and vaccination regimens. To assess immunological readouts for association with a reduced parasite multiplication rate. PCR-derived parasite multiplication rate (PMR) will also be the efficacy endpoint for assessing the durability of the vaccine-reduction in PMR, and comparison of this PMR endpoint between Groups 7, 8 and 9 will constitute this secondary analysis for efficacy. ; Timepoint(s) of evaluation of this end point: Groups 1, 2 & 4 (humoral and cellular immunogenicity): Days 0, 1, 7, 14, 28, 29, 35, 42, 56, 57, 63, 70, 84, 140 and 240 Group 3 (humoral and cellular immunogenicity): Days 0, 1, 7, 14, 28, 29, 35, 42, 56, 182, 183, 189, 196, 210, 266 and 366 Group 5 (humoral and cellular immunogenicity + immunological readouts for reduced PMR after malaria challenge): Days 0, 1, 7, 14, 29, 35, 42, 57, 63, 69 (C-1), day of diagnosis, C+28, C+90 where 'C' refers to malaria controlled human malaria infection (CHMI/challenge)- to take place on day 70 - 84. | — |
Countries
United Kingdom
Contacts
Public ContactAngela Minasian
University of Oxford
Outcome results
None listed