Phase I Study of AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909 Malaria Vaccine

AMA1-C1 + CPG 7909 is a blood stage malaria vaccine candidate. The objectives of this Phase 1 study are to confirm the previously demonstrated safety and immunogenicity of AMA1-C1 + CPG 7909 formulated in a phosphate buffer. In addition, this study will evaluate the safety and immunogenicity of AMA1-C1 + CPG 7909 formulated in a saline buffer, and determine if the addition of CPG 7909 in a saline buffer enhances the immune response to AMA1-C1 in a manner similar to that seen with the addition of CPG 7909 in a phosphate buffer. The immunological effect of giving a second dose of vaccine at 1 or 2 months will also be evaluated. The study is a double blind Phase 1 clinical trial in healthy adult volunteers. Volunteers will be screened and 24 participants will be enrolled and randomly assigned to 1 of 4 groups in a 2x2 design: 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (phosphate) at a 1-month dosing interval; 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (saline) at a 1 month dosing interval; 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (phosphate) at a 2-month dosing interval; and 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (saline) at a 2 month dosing interval. Safety outcome measures are local and systemic (including laboratory) adverse events. Immune responses to vaccination will be measured by enzyme-linked immunosorbent assay (ELISA) and parasite growth inhibition assay (GIA), and will be compared among groups.

• INCLUSION CRITERIA:

Age between 18 and 50 years, inclusive.

Good general health as determined by review of medical history and/or clinical tests at screening.

Available for the duration of the trial (30 weeks).

Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion criteria

• Pregnancy as determined by a positive urine beta-hCG at any time during the study (if female).
• Participant unwilling to use reliable contraception methods for at least 2 weeks prior to vaccination and for the duration of the trial. Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female).
• Currently breast-feeding (if female).
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol.
• Neutropenia as defined by an absolute neutrophil count less than 1500/mm(3).
• Alanine aminotransaminase (ALT) level above the laboratory-defined upper limit of normal.
• Serum creatinine level above the laboratory-defined upper limit of normal.
• Hemoglobin below the laboratory-defined lower limit of normal, by sex.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
• Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the subject unable to comply with the protocol.
• History of receiving any investigational product within the past 30 days.
• Participant has had medical, occupational or family problems as a result of alcohol or illicit drug use during the past 12 months.
• History of a severe allergic reaction or anaphylaxis.
• Positive ELISA and confirmatory Western blot tests for HIV-1.
• Positive ELISA and confirmatory immunoblot tests for hepatitis C virus (HCV).
• Positive hepatitis B surface antigen (HBsAg) by ELISA.
• Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia.
• Known immunodeficiency syndrome.
• Positive serum anti-dsDNA titer.
• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
• Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
• History of a surgical splenectomy.
• Receipt of blood products within the past 6 months.
• Previous receipt of an investigational malaria vaccine.
• Receipt of antimalarial prophylaxis during the past 12 months, or receipt of chloroquine or related compounds (amodiaquine or primaquine) in the previous 8 weeks prior to study entry.
• Prior malaria infection.
• Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives.
• History of a known allergy to nickel.