Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Evaluating Different Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults

This is an interventional prevention trial for Malaria focused on measuring healthy volunteers, Malaria, malaria vaccine, controlled human challenge, RTS,S/AS01 Read More

Inclusion Criteria:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing of any study specific procedure.
• A male or female between, and including, 18 and 55 years of age at the time of enrolment.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Available to participate for the duration of the study.

• Female subjects of non-childbearing potential may be enrolled in the study.

  - Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

• Female subjects of childbearing potential may be enrolled in the study, if the subject:

  • has practiced adequate contraception for 30 days prior to vaccination, and
  • has a negative pregnancy test at enrolment, and
  • has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series and/or malaria challenge.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period.
• Chronic use of antibiotics with antimalarial effects.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
• Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Documented HIV-positive subject.
• Previous vaccination against malaria.
• History of malaria chemoprophylaxis within 60 days prior to vaccination.
• Any history of malaria (for the vaccine groups).
• Planned travel to malaria endemic areas during the study period.
• History of splenectomy.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Family history of congenital or hereditary immunodeficiency.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• History of anaphylaxis post-vaccination.
• Hypersensitivity to latex.
• History of any reaction or hypersensitivity likely to be exacerbated by chloroquine.
• History of psoriasis and porphyria, which may be exacerbated after chloroquine treatment.
• Current use of medications known to cause drug reactions to chloroquine.
• History of severe reactions to mosquito bites.
• Major congenital defects.
• Serious chronic illness.
• History of any neurological disorders or seizures.

• Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route.

  - Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Any abnormal baseline laboratory screening tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, hemoglobin, platelet count, total white blood cells (WBC), out of normal range as defined in the protocol.
• Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the National health and nutrition examination survey I criteria.
• Hepatomegaly, right upper quadrant abdominal pain or tenderness.
• Personal history of autoimmune disease.
• Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
• Pregnant or lactating female.
• History of chronic alcohol consumption and/or drug abuse.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of blood donation within 56 days preceding enrolment.
• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.