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
Condition: Malaria
MeSH terms: Malaria
Intervention: RTS,S/AS01E; RTS,S/AS01B; Sporozoite-infected mosquitoes challenge.
Intervention description: Subjects will receive intramuscular injection of RTS,S/AS01E.; Subjects will receive intramuscular injection of RTS,S/AS01B.; Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 154.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: healthy volunteers; Malaria; malaria vaccine; controlled human challenge; RTS,S/AS01

Summary:

      This study is designed to evaluate efficacy, immunogenicity and safety of various dose
      schedules of GSK Biologicals' candidate malaria vaccines RTS,S/AS01B (adult formulation) and
      RTS,S/AS01E (pediatric formulation) in healthy malaria-naïve subjects aged 18-55 years. The
      purpose of this study is to investigate whether changes in dosing schedule are associated
      with increased or equivalent protection, and to evaluate the immune mechanisms associated
      with vaccine efficacy under varying dosing schedules.
    

Eligibility criteria:

        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.