A Phase I/IIa Sporozoite Challenge Study to Assess the Safety, Immunogenicity and Protective Efficacy of Adjuvanted R21, Administered in Different Dose Schedules in Healthy UK Volunteers
A Phase I/IIa Sporozoite Challenge Study to Assess the Safety, Immunogenicity and Protective Efficacy of Adjuvanted R21, Administered in Different Dose Schedules in Healthy UK Volunteers
An open label, partially blinded clinical trial in which healthy volunteers will be administered experimental malaria vaccines. There will be seven experimental groups of volunteers, of which five receive vaccination with the novel malaria vaccine candidate, R21, in combination with the vaccine adjuvant, Matrix M.
The study will assess the safety & immune responses to vaccination, and the efficacy of the vaccine.
Arms 1a & 1b receive vaccines at 3 vaccinations at 4 week intervals and a booster vaccination approximately 12 months after the first vaccination.
Arms 2a & 2b receive 3 vaccinations at 0, 4 and 24 weeks. The protected volunteers in 2a from the first malaria challenge, VAC072A, will receive a booster vaccination 28 days before the rechallenge, VAC072B.
Arms 3a and 3b receive 3 vaccinations at 0, 4 and 8 weeks. The protected volunteers in 3a from the first malaria challenge, VAC072A, will receive a booster vaccination 28 days before the rechallenge, VAC072B.
Arms 4a and 4b will receive 3 vaccinations at 0, 4 and 24 weeks. The third dose is fractional. Volunteers then have the option to be challenged 28 days after final vaccination.
Group 5 will receive 3 vaccinations at 0, 4 and 24 weeks. The third dose is fractional. Volunteers then have the option to be challenged 28 days after final vaccination.
Groups 6 & 7 are control groups and will receive controlled human malaria infection (CHMI)
Healthy volunteers will be recruited in England across four research sites in Oxford, London, and Southampton.
Inclusion Criteria:
Exclusion Criteria:
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.
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) 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 25 standard UK units every week.
Suspected or known injecting drug abuse in the 5 years preceding enrolment.
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).
Positive family history in both 1st and 2nd degree relatives < 50 years old for cardiac disease.*
Volunteers unable to be closely followed for social, geographic or psychological reasons.
Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in Appendix A.
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.