Plasmodium falciparum infection
Conditions
Interventions
Product Name: R21
Pharmaceutical Form: Solution for injection
INN or Proposed INN: R21
Other descriptive name: R21c
Concentration unit:
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. • Women only: Must practice continuous effective contraception* for the duration of the study. • Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study. • Written informed consent to participate in the trial. • Reachable (24/7) by mobile phone during the period between CHMI and completion of antimalarial treatment. • Willingness to take a curative anti-malaria regimen following CHMI. • For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (from at least day 6.5 post mosquito bite until anti-malarial treatment is completed). • Answer all questions on the informed consent quiz correctly. *Female volunteers are required to use an effective form of contraception during the course of the study as there is no information about the effect of these vaccines on a foetus. Acceptable forms of contraception for female volunteers include: • Established use of oral, injected or implanted hormonal methods of contraception. • Placement of an intrauterine device (IUD) or intrauterine system (IUS). • Total abdominal hysterectomy • Barrier methods of contraception (condom or occlusive cap with spermicide) • Male sterilisation, if the vasectomised partner is the sole partner for the subject. • True abstinence, when this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence and withdrawal are not acceptable methods of contraception). 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 78 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: • History of clinical malaria (any species). • Travel to a clearly malaria endemic locality during the study period or within the preceding six months • Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin) • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. • Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data as assessed by the investigator. For group 6 volunteers, or if any volunteers in Groups 1, 2, 3 or 5 undergo rechallenge, this exclusion criterion does not extend to the vaccines previously received in the VAC065 or VAC053 trials • For Group 3 volunteers only: prior receipt of a non-malaria MVA or non-malaria adenovirus vectored experimental vaccine • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). • Use of immunoglobulins or blood products within 3 months prior to enrolment. • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products, Kathon) or malaria infection. • Any history of anaphylaxis post vaccination. • History of clinically significant contact dermatitis. • History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection. • Pregnancy, lactation or intention to become pregnant during the study. • 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 • Any clinical condition known to prolong the QT interval and existing contraindication to the use of Malarone. • History of cardiac arrhythmia, including clinically relevant bradycardia and existing contraindication to the use of Malarone. • Clinically significant disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia • Family history of congenital QT prolongation or sudden death and existing contraindication to the use of Malarone. • Contraindications to the use of both Riamet and Malarone • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). • History of serious psychiatric condition that may 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 standard UK units every week. • Suspected or known injecting drug abuse in the 5 years preceding enrolment. • Hepatiti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is a clinical trial in which healthy volunteers will be administered experimental malaria vaccines. Three groups of volunteers will receive vaccination with the novel malaria vaccine candidate, R21 at three different dose schedules given in combination with the vaccine adjuvant, Matrix-M1. Vaccines will be delivered at 4 week intervals (ie. At 0, 4 & 8 weeks). A fourth group will receive 10ug R21 with Matrix M1 at 0, 4 and 8 weeks in combination with ChAd63 ME-TRAP and MVA ME-TRAP given at 1 and 9 weeks, respectively. A fifth group will receive a 2-doe schedule of 10/10ug R21/Matrix-M given 4 weeks apart. The vaccine schedule containing R21 alone, and ChAd63 ME-TRAP and MVA ME-TRAP have been tested independently in clinical trials, however, the vaccine schedule containing both R21, ChAd63 ME-TRAP and MVA ME-TRAP has not yet been tested. The first principal research objective is to measure how well this new malaria vaccine strategy acts to prevent malaria disease. This is called e; Secondary Objective: The secondary objective is to assess the immune responses to these vaccination strategies. We will do this by taking blood from volunteers who have received the vaccines and doing tests on it, such as measuring the number of immune cells that are induced by the vaccines. Another secondary objective is to assess the length of time taken to malaria diagnosis as a secondary measure of vaccine effect. ; Primary end point(s): To assess the efficacy (occurrence of P. falciparum parasitemia, assessed by blood slide) of R21 plus Matrix M, and of R21 plus Matrix M administered in combination with ChAd63 ME-TRAP and MVA ME-TRAP, against malaria sporozoite challenge, in healthy malaria-naïve volunteers. To assess the safety of R21 plus Matrix-M1, and of R21 plus Matrix-M1 administered in combination with ChAd63 ME-TRAP and MVA ME-TRAP, in healthy malaria-naïve volunteers. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess immunogenicity generated in malaria naïve individuals of R21 plus Matrix M, and of R21 with Matrix M administered in combination with ChAd63 ME-TRAP and MVA ME-TRAP. To assess the efficacy (measured as time to P. falciparum parasitemia assessed by blood slide, by PCR, and parasite density dynamics assessed by PCR) of R21 with Matrix M, and of R21 with Matrix M administered in combination with ChAd63 ME-TRAP and MVA ME-TRAP, against malaria sporozoite challenge, in healthy malaria-naïve volunteers. ; Timepoint(s) of evaluation of this end point: Immunology investigations will be collected on blood specimens taken from volunteers across the course of their participation in the trial. PCR data will be collected from Day 6.5 to day 21 (or until malaria diagnosis) to establish time to 20 parasites per ml and time to 500 parasites per ml. | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Adrian Hill
University of Oxford
Outcome results
None listed