AMA1-C1/Alhydrogel + CpG 7909 for Malaria
Condition: Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to test an experimental malaria vaccine in about 75 healthy
      adults, 18-45 years of age. The study will also test an experimental adjuvant which is a
      material added to a vaccine to help the body make more defense cells. The body's immune
      response (response to foreign substances) and the safety of the vaccine will be tested. All
      subjects will receive 3 doses of vaccine on days 0, 28, and 56 and doses may increase during
      the study. Participation in the study is expected to be up to 323 days and includes 16
      visits. Study procedures include medical history, physical exams, urine and blood testing.
    

Detailed description: 
      This phase I, dose escalating study will evaluate the safety and immunogenicity of the
      experimental malaria vaccine AMA1-C1/Alhydrogel®, and the ability of the TLR-9 agonist CPG
      7909 oligodeoxynucleotide (ODN) to augment antibody responses to the vaccine and alter the
      Th1/Th2 bias. The vaccine preparations to be studied contain an equal mixture of AMA1 from
      two different clones of Plasmodium falciparum (FVO and 3D7). Subjects will be randomly
      assigned to receive Alydrogel® formulated vaccine with or without CPG 7909 in a point of use
      formulation. The study will be conducted at the University of Rochester Vaccine and Treatment
      Evaluation Unit. Subjects for this study will be healthy adults between the ages of 18 and 45
      years with no history of malaria or of recent travel to malaria-endemic areas. Subjects will
      be enrolled in three consecutive dose-escalation cohorts with review by a Safety Monitoring
      Committee between cohorts. Subjects will receive 3 vaccinations with the AMA1-C1/Alhydrogel®
      vaccine formulated in Alhydrogel® with or without CPG 7909 adjuvant over 2 months (0, 1, 2
      months) by intramuscular (IM) injection. Subjects will have multiple blood samples obtained
      over the next 6 months. The primary objective of the study is to assess the safety,
      reactogenicity of the AMA1-C1/Alhydrogel® + CPG 7909 vaccine. The secondary objectives of the
      study include the following: to demonstrate that the addition of CPG 7909 improves the immune
      responses to AMA1-FVO and AMA1-3D7, as compared to AMA1-C1/Alhydrogel® at day 70 (14 days
      after 3rd vaccination; to determine the dose of AMA1-C1/Alhydrogel® + CPG 7909 that generates
      the highest serum antibody levels of AMA-FVO and AMA1-3D7 at day 70; to assess and compare
      the duration of antibody responses to AMA1-FVO and AMA1-3D7 proteins by enzyme-linked
      immunosorbent assay (ELISA) over an 8 month period (6 months after 3rd vaccination); and to
      perform exploratory studies of B and T cell populations both before and after vaccination.
      The safety trial endpoints include the frequency and severity of local and systemic adverse
      events after each dose reported on the subject diary card (solicited adverse events) or
      reported by subjects spontaneously (unsolicited adverse events) and the presence of abnormal
      clinical laboratory tests after immunization in each group. The immunogenicity endpoints
      include the frequency and titer of vaccine induced neutralizing and binding antibody, and the
      presence and quantity of antigen-specific B cells and CD4 and CD8 T cells producing specified
      cytokines following vaccination.
    

Intervention name(s): AMA1-C1/Alhydrogel®; CPG 7909 Oligodeoxynucleotide (VaxImmune®)
Intervention type(s): Biological; Biological
Intervention description(s): AMA1-C1/Alhydrogel malaria vaccine, cloudy suspension, 0.5 mL dose containing up to equivalent of 377 mcg of aluminum as Alhydrogel® (800 mcg of aluminum hydroxide gel per dose) onto which 20 mcg or 80 mcg of recombinant AMA1-C1 is bound. Dosages: 20 mcg and 80 mcg administered via the deltoid muscle by IM injection; CPG 7909 is an investigational agent and is supplied in sterile vials at 10mg/mL in phosphate buffered saline for intramuscular administration. Dosage 500 mcg.
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: asexual blood stage vaccine, Plasmodium falciparum malaria