Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults
Condition: Malaria
MeSH terms: Malaria
Intervention: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01); GSK Biologicals' malaria vaccine 257049 (2 doses); GSK Biologicals' malaria vaccine 257049 (3 doses); Sporozoite challenge
Intervention description: One dose will be administered intramuscularly at Study Day 0.; Two doses will be administered intramuscularly at monthly intervals; Three doses will be administered intramuscularly at monthly intervals; Subjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: safety; Vaccine; Phase 1/2; immunogenicity; Malaria; efficacy; sporozoite challenge

Summary:

      This study will evaluate whether administration of two investigational malaria vaccines
      (257049 and Ad35.CS.01 vaccines) combined in one immunization schedule increases protection
      against malaria infection as compared to protection induced by the 257049 vaccine alone. The
      study will also evaluate the safety and the immune response to the new combination of the two
      experimental malaria vaccines.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who the investigator believes 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.

          -  Female subjects of non-childbearing potential.

          -  Female subjects of childbearing potential may be enrolled in the study, if the
             subject:

               -  has practiced adequate Food and Drug Administration (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.

          -  Pass a comprehension assessment test.

        Exclusion Criteria:

          -  Use of any investigational or non-registered product within 30 days preceding the
             first dose of study vaccine, or planned use of any investigational or non-registered
             product other than the study vaccines 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 or adenovirus 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, such as
             antacids and kaolin.

          -  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.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, including
             immunodeficiency virus (HIV) infection.

          -  Family history of congenital or hereditary immunodeficiency.

          -  History of splenectomy.

          -  Major congenital defects or serious chronic illness.

          -  History of any neurological disorders or seizures.

          -  Acute disease and/or fever at the time of enrollment.

          -  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.

          -  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.

          -  Evidence of increased cardiovascular disease risk, "moderate" or "high", according to
             the NHANES I criteria.

          -  An abnormal baseline screening electrocardiogram (EKG).

          -  Hepatomegaly, right upper quadrant abdominal pain or tenderness.

          -  Personal history of autoimmune disease.

          -  Seropositive for hepatitis B surface antigen or Hepatitis C virus (antibodies to HCV).

          -  Pregnant or lactating female.

          -  Female who intends to become pregnant during the study or planning to discontinue
             contraceptive measures.

          -  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.