A Study to Evaluate the Efficacy, Immunogenicity and Safety in a Sporozoite Challenge Model of a Fractional Booster Dose of GSK Biologicals' Candidate Malaria Vaccine Administered to Previously Vaccinated Healthy Malaria-naïve Adults
Condition: Malaria
MeSH terms: Malaria
Intervention: RTS,S/AS01E (SB257049)
Intervention description: Subjects from the P-Fx and NP-Fx groups will receive one Fx booster dose of RTS,S/AS01E at Day 1.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Malaria; RTS,S/AS01E vaccine; Fractional dose; Sporozoite challenge

Summary:

      MALARIA-092 (NCT03162614) study was designed to evaluate the efficacy, immunogenicity and
      safety of various dose schedules and formulations of GSK Biologicals' candidate malaria
      vaccine (RTS,S/AS01E) in healthy malaria-naïve subjects aged 18-55 years.

      The purpose of this study (follow-up to MALARIA-092 [NCT03162614] study) is to evaluate if
      protection can be extended with an additional Fx booster dose and if unprotected subjects can
      be protected following a Fx booster dose.

      In this booster study, subjects from MALARIA-092 (NCT03162614) study who completed
      vaccination and challenge will receive a Fx booster dose of RTS,S/AS01E and undergo a second
      controlled human malaria infection (CHMI) three to four weeks after vaccination.
      Additionally, subjects will be newly enrolled and will only undergo the sporozoite challenge
      as infectivity controls.
    

Eligibility criteria:

        Inclusion Criteria:

        Only for subjects from MALARIA-092 study (NCT03162614):

        • Subjects vaccinated and having undergone sporozoite challenge during the primary study
        (MALARIA-092 [NCT03162614]).

        For all subjects:

          -  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 any
             study-specific procedure.

          -  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.

          -  Female subjects of childbearing potential may be enrolled in the study, if the
             subject:

               -  Has practiced adequate contraception for 30 days prior to Day 1, and has agreed
                  to continue adequate contraception during the entire treatment period and for two
                  months after malaria challenge (only for subjects from the MALARIA-092 study
                  [NCT03162614]).

               -  Has practiced adequate contraception for 30 days prior to malaria challenge, and
                  has agreed to continue adequate contraception up to two months after malaria
                  challenge (only for the infectivity control subjects).

               -  Has a negative pregnancy test at enrollment.

        For the infectivity control subjects:

        • Male or female subjects between, and including, 18 and 55 years of age.

        Exclusion Criteria:

        For all subjects except the infectivity control subjects:

          -  Any medical condition that in the judgment of the investigator would make
             intramuscular injection unsafe.

          -  History of any reaction or hypersensitivity likely to be exacerbated by any component
             of the vaccine.

          -  History of anaphylaxis post-vaccination.

        For all subjects:

          -  Use of any investigational or non-registered product other than the study vaccine
             during the period starting 30 days before Day 1 (Day -29 to Day 1) (for P-Fx and NP-Fx
             groups)/before the malaria challenge (for infectivity control subjects), or planned
             use during the study period.

          -  Chronic administration of immunosuppressants or other immune-modifying drugs during
             the period starting six months prior to Day 1 (for P-Fx and NP-Fx groups) or malaria
             challenge (for infectivity control subjects). 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 anti-malarial effects.

          -  Planned administration/administration of a vaccine not foreseen by the study protocol
             in the period within seven days of Day 1 (for P-Fx and NP-Fx groups) or the malaria
             challenge (for infectivity control subjects).

          -  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 Human Immunodeficiency Virus, Hepatitis B surface antigen or
             Hepatitis C Virus.

          -  Planned travel to malaria endemic areas during the study period.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and physical examination.

          -  History of any reaction or hypersensitivity that would prevent the subject from
             utilizing all of the following: chloroquine, atovaquone/proguanil,
             artemether/lumefantrine.

          -  Current use of medications known to cause drug reactions that would prevent the
             subject from utilizing any of the following: chloroquine, atovaquone/proguanil,
             artemether/lumefantrine.

          -  History of severe reactions to mosquito bites.

          -  Acute disease and/or fever at the time of enrollment.

               -  Fever is defined as temperature ≥37.5°C/99.5°F for oral, axillary or tympanic
                  route.

               -  Subjects with a minor illness without fever may be enrolled at the discretion of
                  the investigator.

          -  Hepatomegaly, right upper quadrant abdominal pain or tenderness.

          -  Any abnormal baseline laboratory screening tests: ALT, AST, creatinine, hemoglobin,
             platelet count, total WBC, out of normal range.

          -  Personal history of auto-immune disease.

          -  Administration of immunoglobulins and/or any blood products during the period starting
             three months before Day 1 (for P-Fx and NP-Fx groups)/the malaria challenge (for
             infectivity control subjects), or planned administration during the study period.

          -  Pregnant or lactating female.

          -  Female planning to become pregnant or planning to discontinue contraceptive
             precautions.

          -  History of chronic alcohol consumption and/or drug abuse.

          -  History of blood donation within 56 days preceding enrollment.

          -  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.

          -  Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
             functional abnormality, as determined by physical examination or laboratory screening
             tests.

          -  Evidence of increased cardiovascular disease risk, "moderate" or "high", according to
             the National Health And Nutrition Examination Survey I (NHANES I) criteria.

        Only for infectivity control subjects:

          -  Previous vaccination against malaria.

          -  History of splenectomy.

          -  Family history of congenital or hereditary immunodeficiency.

          -  Major congenital defects.

          -  Serious chronic illness.

          -  History of any neurological disorders or seizures.

          -  Diagnosed with malaria within the last 5 years (inclusive).