Efficacy, Safety and Immunogenicity Study of GlaxoSmithKline(GSK) Biologicals' Candidate Malaria Vaccine 257049 in the Sporozoite Challenge Model in Healthy Malaria-naïve Adults
Condition: Malaria
MeSH terms: Malaria
Intervention: GSK257049 Dosage 1; GSK257049 Dosage 2; Sporozoite-infected mosquitoes challenge
Intervention description: RTS,S/AS01B administered as 0.5 mL dose at 0 and 1 months and 0.1 mL dose at 7 months for 0,1,7 M Group (delayed fractional dose group). In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.; RTS,S/AS01B administered as three doses of 0.5mL given one month apart (0, 1, 2 M group) in the challenge model. In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.; Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the volunteers. For each volunteer, 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.
The challenge is scheduled to occur approximately 21 days (3 weeks) after the last vaccination visit (Study Day 196). Volunteers who reconsent for the boost/rechallenge phase will be rechallenged with sporozoite-infected mosquitoes, scheduled to occur approximately 21 days (3 weeks) after the booster dose (Booster Phase Study Day 21).
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Efficacy; Sporozoite challenge model; Malaria; Immunogenicity; Malaria- naïve adults; Safety

Summary:

      This study is designed to evaluate safety, reactogenicity, immunogenicity, and efficacy of
      GSK Biological's malaria candidate vaccine 257049 administered as standard doses at 0 and 1
      months and 1/5th standard dose at 7 months (delayed fractional dose group) and 257049
      administered as three standard doses one month apart (0, 1, 2-month group) in healthy
      malaria-naïve volunteers aged 18-50 years in the sporozoite challenge model.

      An additional, delayed sporozoite challenge will assess persistence of protection induced by
      the primary immune schedule and if an additional dose can provide protection in those
      unprotected by the initial vaccination series.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion criteria for enrolment to the primary phase:

          -  Subjects who, in the opinion of the investigator, can and will comply with the
             requirements of the protocol.

          -  A male or non-pregnant female 18 to 50 years of age at the time of first vaccination.

          -  Written informed consent obtained from the subject before screening procedures.

          -  Free of obvious health problems as established by medical history and clinical
             examination before entering into the study.

          -  Available to participate for the duration of the study (approximately 15 months per
             vaccinated subject in the delayed fractional dose group, approximately 10 months per
             vaccinated subject in the 0, 1, 2-month schedule and approximately 7 months per
             subject in the infectivity control group).

          -  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 FDA-approved contraception for 30 days prior to
                  vaccination, and

               -  has a negative pregnancy test on the day of vaccination, and

               -  has agreed to continue adequate FDA-approved contraception during the entire
                  treatment period and for 2 months after completion of the vaccination series
                  and/or malaria challenge.

        Inclusion criteria for enrolment to the booster phase:

          -  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 before screening procedures.

          -  Subjects vaccinated in the primary phase of the study (not applicable to new
             infectivity controls), having undergone sporozoite challenge during the primary phase
             of the study.

          -  Available to participate for the duration of the booster phase of the study
             (approximately 3 months).

          -  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 booster phase of the
             study, if the subject:

               -  has practiced adequate FDA-approved contraception for 30 days prior to day of
                  booster vaccination, and

               -  has a negative pregnancy test on the day of booster vaccination, and

               -  has agreed to continue adequate FDA-approved contraception during the entire
                  treatment period and for 2 months after completion of the booster vaccination
                  and/or malaria rechallenge.

        Exclusion Criteria:

        For enrolment to the primary & booster phase:

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, including
             immunodeficiency virus (HIV) infection.

          -  Acute disease and/or fever at the time of enrolment to booster phase.

               -  Acute disease is defined as the presence of a moderate or severe illness with or
                  without fever. Subjects with a minor illness without fever may be enrolled at the
                  discretion of the investigator.

               -  Fever is defined as temperature ≥ 38.0°C (100.4°F) on oral, axillary or tympanic
                  setting. The preferred route for recording temperature in this study will be
                  oral.

          -  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.

        Note: NHANES I criteria will be applied for all subjects including subjects aged 18-35
        years old.

          -  An abnormal baseline screening electrocardiogram (EKG), defined as one showing
             pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy;
             any non-sinus rhythm excluding isolated premature atrial contractions; right or left
             bundle branch block; or advanced A-V heart block.

          -  Female who intends to become pregnant during the study or planning to discontinue
             contraceptive measures.

        For enrolment to the primary phase:

          -  Use of any investigational or non-registered product other than the study vaccine
             within 30 days preceding the first dose of study vaccine, or planned use during the
             study period.

          -  Planned administration/administration of a vaccine not foreseen by the study protocol
             within 7 days of the first dose of vaccines.

          -  Prior receipt of an investigational malaria vaccine.

          -  Chronic use of antibiotics with antimalarial effects.

          -  History of malaria chemoprophylaxis within 60 days prior to vaccination.

          -  Any history of malaria.

          -  Planned travel to malaria endemic areas during the study period.

          -  History of allergic disease or reactions likely to be exacerbated by any component of
             the vaccine(s) including latex.

          -  History of allergic disease or reactions 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.

          -  Any history of anaphylaxis in reaction to any previous vaccination.

          -  History of severe reactions to mosquito bites.

          -  Administration of immunoglobulins and/or any blood products within the three months
             preceding the first dose of study vaccine or planned administration during the study
             period.

          -  Chronic administration of immunosuppressants or other immune modifying drugs within
             six months prior to first vaccine dose. For corticosteroids, this will mean
             prednisone, or equivalent, greater than or equal to 20 mg/day. Inhaled and topical
             steroids are allowed.

          -  Family history of congenital or hereditary immunodeficiency.

          -  History of splenectomy.

          -  Major congenital defects or serious chronic illness.

          -  History of any neurological disorders or seizures, except for a single episode of
             simple febrile seizure in childhood.

          -  Any abnormal baseline laboratory screening tests: Alanine aminotransferase (ALT),
             Aspartate aminotransferase (AST), creatinine, hemoglobin, platelet count, total white
             blood cell count, out of normal range as defined in the protocol.

          -  Hepatomegaly, right upper quadrant abdominal pain or tenderness.

          -  Personal history of autoimmune disease.

          -  Seropositive for hepatitis B surface antigen or Hepatitis C virus.

          -  Pregnant or lactating female.

          -  Suspected or known current alcohol abuse.

          -  Chronic or active intravenous drug use.

          -  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.

        For enrolment to the booster phase:

          -  Planned use of any investigational or non-registered product other than the study
             vaccine during the study period.

          -  Planned administration/administration of a vaccine not foreseen by the study protocol
             within 7 days of booster dose of study vaccine.

          -  Planned administration of immunoglobulins and/or any blood products during the study
             period.

          -  An abnormal baseline laboratory screening test, graded 2 or more as defined in the
             protocol.

          -  Any abnormal baseline laboratory screening tests out of normal range as defined in the
             protocol and of clinical concern according to the Principal Investigator.

          -  Any other significant finding that in the opinion of the investigator would increase
             the risk of having an adverse outcome from participating in the booster phase of the
             study.