Phase 1 Study of the Safety, Reactogenicity, and Immunogenicity of AMA1-C1/ISA 720: Blood Stage Vaccine for Plasmodium Falciparum
Phase 1 Study of the Safety, Reactogenicity, and Immunogenicity of AMA1-C1/ISA 720: Blood Stage Vaccine for Plasmodium Falciparum
This study will evaluate the safety and effectiveness of a vaccine called AMA1-C1/ISA.
 Malaria is a serious infection of red blood cells caused by a parasite. There are 300 to 500
 million malaria cases worldwide each year. About 2 to 3 million deaths annually are from
 malaria alone or along with other diseases. Researchers hope to find a vaccine to fight
 malaria.

 Patients ages 18 to 45 who are in good health, are not pregnant or breast feeding, have no
 history of malaria, and have not lived for more than 1 month in an area where malaria is
 prevalent may be eligible for this study. There will be 28 participants, each assigned to one
 of three dose groups: 12 get 5 microg, 12 get 20 microg, and 4 get 80 microg of AMA 1-C1
 formulated in ISA 720. The vaccine might block the parasite from entering red blood cells and
 causing disease. This study is the first time the vaccine will be given to human beings for
 testing.

 Patients will have a medical history, physical exam, laboratory tests, and pregnancy tests.
 The study will last 48 weeks. One or two vaccinations are given by injection, at least 12
 weeks apart. After each vaccination, patients will be asked to stay in the clinic for at
 least 30 minutes for observation. They will return to the clinic on Days 1, 3, 7, 14, 28, and
 56 after each vaccination. There will be a check of vital signs, brief physical exam, history
 of symptoms and medications taken since the last visit, and blood tests to check for vaccine
 safety and effectiveness. Photographs of the injection site on the arm may be taken. Patients
 will receive a thermometer, diary card, and plastic measuring device. Each day they will
 record their temperatures and any symptoms, and measure the size of any reactions at the
 vaccination site. They will be asked to do this for 27 days after vaccinations.

 After injections, there may be pain, swelling, and redness at the vaccination site, and
 limitation of arm movement. General side effects from the vaccine may be fever, chills,
 headache, fatigue, and muscle and joint pain. Patients will be asked if they agree to have
 researchers keep any unused serum samples, for use only in research into malaria and other
 diseases. Genetic testing would not be done on those samples. Stored samples will be labeled
 with a code, and information is kept private.
AMA1-C1 with Montanide ISA 720, is a blood stage malaria vaccine candidate. The objectives of
 this phase 1 trial are to study the safety, reactogenicity, and immunogenicity of this
 vaccine and to assess the level, kinetics, and the in vitro biological activity of the
 antibody response it induces. The study is an open label, dose escalation, phase 1 clinical
 trial in healthy adult volunteers. Volunteers will be screened and 28 participants will be
 enrolled into 3 dose cohorts. Cohort 1 will receive 5 micrograms of AMA1-C1/ISA 720 at each
 injection, Cohort 2 will receive 20 micrograms, and Cohort 3 will receive 80 micrograms.
 Cohorts 1 and 2 will receive 2 injections, 3 months apart. Cohort 3 will receive only 1
 vaccination. 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 dose groups.
-  INCLUSION CRITERIA:

 1. Males or females between 18 and 45 years, inclusive.

 2. Good general health as determined by means of the screening procedure.

 3. Available for the duration of the trial (48 weeks).

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

 5. For female subjects: Negative pregnancy tests at Screening and Day 0, in
 conjunction with a history indicating a low probability of pregnancy in the
 opinion of the physician. Sexually active females of childbearing potential will
 be required to be correctly using an efficacious method of contraception for at
 least 1 month before randomization and during the on-study phase to Month 7.
 Female subjects unable to become pregnant must have this documented (e.g. tubal
 ligation, hysterectomy, or postmenopausal [at least one year since last menstrual
 period]).

 EXCLUSION CRITERIA:

 1. History of malaria, residence for more than 1 month in a malaria endemic area (as
 determined by interview), or plans to visit a malaria endemic area during the study
 period.

 2. For female subjects: Positive pregnancy test at screening or Day 0, as well as those
 currently lactating and breast feeding.

 3. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
 rheumatologic, chronic infectious or renal disease by history, physical examination,
 and/or laboratory studies including urinalysis.

 4. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
 affects the ability of the volunteer to understand and cooperate with the study
 protocol.

 5. Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25
 times the upper limit of normal of the testing laboratory).

 6. Laboratory evidence of renal disease (serum creatinine greater than the upper limit of
 normal of the testing laboratory, or more than trace protein or blood on urine
 dipstick testing confirmed by repeat testing of clean-catch, midstream sample). (More
 than trace blood on urine dipstick will not exclude a female who is actively
 menstruating).

 7. Laboratory evidence of hematologic disease (absolute leukocyte count less than
 3000/mm(3) or greater than 11,500/mm(3); hemoglobin less than 0.9 times the lower
 limit of normal of the testing laboratory, by gender; absolute granulocyte count less
 than 1300/mm(3); absolute lymphocyte count less than 1000/mm(3); or platelet count
 less than 11,000/mm(3)).

 8. Other condition that, in the opinion of the investigator, would jeopardize the safety
 or rights of a volunteer participating in the trial or would render the subject unable
 to comply with the protocol.

 9. Participation in another investigational vaccine or drug trial within 30 days of
 starting this study, or while this study is ongoing.

 10. Volunteer has had medical, occupational, or family problems as a result of alcohol or
 illicit drug use during the past 12 months.

 11. History of a severe allergic reaction or anaphylaxis.

 12. Severe asthma. This will be defined as:

 -  Asthma that is unstable or required emergent care, urgent care, hospitalization
 or intubation during the past two years or that requires the use of oral or
 parenteral corticosteroids.

 -  Clinically significant reactive airway disease that does not respond to
 bronchodilators.

 13. Positive ELISA for anti-HCV.

 14. Positive hepatitis B surface antigen (HBsAg) by ELISA.

 15. Positive ELISA for anti-HIV.

 16. Use of systemic corticosteroids (excluding topical or nasal) or immunosuppressive
 drugs within 30 days of starting this study.

 17. Receipt of a live vaccine within past 4 weeks or non-live vaccine within past 2 weeks
 prior to entry into the study.

 18. History of a surgical splenectomy.

 19. Receipt of blood products within the past 6 months.

 20. Previous receipt of an investigational malaria vaccine.

 21. History of a known allergy to nickel.