Adenovirus Vaccine for Malaria
Condition: Plasmodium Falciparum Infection
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Malaria is caused by a parasite carried by a mosquito. Currently, there is no vaccine
      licensed to prevent malaria. The purpose of this study is to find the most effective and
      safest dose of an experimental vaccine for the treatment of malaria. Participants will
      include 72 healthy adults, ages18 to 45, enrolled at Vanderbilt University Medical Center and
      Stanford University. Volunteers will receive 3 doses of either the malaria vaccine or placebo
      (contains no vaccine) by injection into a muscle at 0, 1 and 6 months. Investigators will
      evaluate how the body responds to increasing dosage strengths of the vaccine. Study
      procedures include physical exam, multiple blood draws, and completion of a memory aid
      (diary). Each participant will be actively involved in the study for about 12 months. Then,
      an annual phone call will be made to check for any serious illness events for a period of 5
      years.
    

Detailed description: 
      Malaria currently represents one of the most prevalent infections in tropical and subtropical
      areas throughout the world. Each year, malaria affects around 300 million people and kills 1
      to 3 million people in developing countries. The widespread occurrence and the growing
      incidence of malaria are a consequence of the increasing numbers of drug-resistant parasites
      and insecticide-resistant parasite vectors. Other factors include environmental and climatic
      changes, civil disturbances and increased mobility of populations. It is hypothesized that
      the Ad35.CS.01 vaccine will prevent the Plasmodium (P.) falciparum parasite, which causes
      malaria, from entering and developing within the liver of those who become infected.
      Ad35.CS.01 would therefore be expected to reduce malaria-attributable morbidity and
      mortality. The purpose of this phase I, randomized, controlled, dosage-escalation trial is to
      evaluate the immunogenicity, safety, and reactogenicity of an Adenovirus Type 35 based
      circumsporozoite malaria vaccine in 72 healthy adults, 18 to 45 years of age, in the United
      States. Subjects will be randomized in a 5:1 ratio to receive 3 doses of the Adenovirus Type
      35 circumsporozoite malaria vaccine (Ad35.CS.01) or normal saline placebo control by the
      intramuscular route at 0, 1 and 6 months. The safety, reactogenicity, and immunogenicity of
      ascending dosages of the vaccine will be assessed. Fifteen subjects will receive vaccine at
      each of the following dosage levels: 10^8 viral particles (vp)/milliliters (ml), 10^9 vp/ml,
      10^10 vp/ml and 10^11 vp/ml with 3 subjects receiving control at each of these dosage levels.
      Dosage escalation will proceed only after review of the safety data by the Safety Monitoring
      Committee of the prior dosage level. The primary objective is to assess the safety and
      reactogenicity of ascending dosages of Adenovirus Type 35 based circumsporozoite malaria
      vaccine among healthy subjects given in 3 intramuscular doses at 0, 1 and 6 months. The
      secondary objective is to evaluate the immunogenicity of the Adenovirus Type 35 based
      circumsporozoite malaria vaccine through performance of Humoral Immune Assays [ELISA
      (enzyme-linked immunosorbent assay)] for antibodies to circumsporozoite antigen and
      Adenovirus Neutralization Assay for neutralizing antibodies to Adenovirus type 35) and
      Cellular Immune Assays [enzyme-linked immunosorbent spot (ELISPOT) and Flow Cytometry] for
      circumsporozoite (CS)-specific cluster of differentiation (CD)4+ and CD8+ T cell responses.
    

Intervention name(s): Placebo; Ad35.CS.01 Circumsporozoite Malaria Vaccine
Intervention type(s): Drug; Biological
Intervention description(s): Normal saline.; Adenovirus Type 35 Circumsporozoite Malaria Vaccine (Ad35.CS.01); administered at 0, 1, and 6 months; dosage levels: 10^8 viral particles (vp)/mL, 10^9 vp/mL, 10^10 vp/mL and 10^11 vp/mL.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: circumsporozoite, malaria, vaccine