Experimental Vaccine for Malaria
This study will examine the safety and immune response of healthy adult volunteers to AMA1-C1, an experimental malaria vaccine developed by the NIAID. Malaria affects about 300 million to 500 million people worldwide each year, causing from 2 million to 3 million deaths. Increasing drug resistance to the malaria parasite, as well as widespread resistance of mosquitoes (the insects that transmit the parasite) to pesticides are reducing the ability to control malaria through these strategies. A vaccine that could reduce illness and death from malaria would be a valuable new resource in the fight against this disease. Early tests of AMA1-C1 in 66 people in the United States and in Mali, West Africa, found no serious side effects of the vaccine. This study will test a shorter schedule of vaccinations with AMA1-C1 than that used in the previous studies.
Healthy volunteers between 18 and 50 years of age who weigh at least 110 pounds and with no travel to malaria endemic areas in the past 12 months may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and a urine pregnancy test for women who are able to bear children.
Participants are randomly assigned to receive three injections of either the experimental malaria vaccine or a placebo (a solution that does not contain the vaccine) over a 2-month period. The shots are given in an upper arm muscle, each 1 month apart. On the day of each injection, participants give a history of symptoms since the last visit, have a brief physical examination and blood test and, for women, a blood or urine pregnancy test. After the injection, participants remain in the clinic 60 minutes for observation. In addition to the injections, participants undergo the following procedures:
- Record temperature and symptoms on a diary card daily for the first 7 days after each injection.
- Follow-up clinic visits 1, 3, 7 and 14 days after each shot to check for side effects. Blood samples are drawn before each injection and at each return clinic visit to check the safety and immune response to the vaccine.
- Have apheresis, a special procedure that separates certain components of the blood, 7 days after each injection to measure the function of germ-fighting blood cells. For this procedure, blood is drawn through a needle in an arm vein and directed into a machine that separates the different types of blood cells. The white cells are collected in a plastic ...
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Masking: Single Blind
Primary Purpose: Treatment
|Official Title:||Phase 1 Study of the Safety of Immunization of Naive Individuals With AMA1-C1/Alhydrogel [R], an Asexual Blood-Stage Vaccine for Plasmodium Falciparum Malaria, and the Effect of Immunization on Antigen-specific Memory and Plasma B Cells and T Cells|
|Study Start Date:||April 2005|
|Study Completion Date:||December 2006|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
The study is a randomized, single-blinded (blinded to volunteers) placebo-controlled Phase 1 clinical trial in healthy adult volunteers designed to evaluate the safety and reactogenicity of a new malaria blood stage vaccine candidate, and to elucidate the immunogenicity of the antigen, AMA1-C1, formulated on Alhydrogel [R]. The trial will last 42 weeks. Volunteers will be recruited and screened, and those determined to be eligible will be enrolled in the study, based on the inclusion and exclusion criteria described in Section 4.0 in this protocol. After providing written informed consent the volunteers will be enrolled and randomly allocated to receive 80 microgram dose of AMA1-C1 formulated on Alhydrogel [R] (12 volunteers) or Alhydrogel [R] alone (6 volunteers) at 0, 1 and 2 months. After each injection, volunteers will be observed for 60 minutes for immediate reactions. Volunteers will return to the clinic on study days 1, 3, 7, and 14 following each injection for clinical assessment and collection of blood samples for evaluation of immune responses. Leukaphereses will be performed 7 days after the third vaccination to obtain peripheral blood mononuclear cells for B and T cell studies. Safety data for the cohort up to and including follow up day 14 after the first, second and third injection will be available for review by the Medical Monitor.
Immunogenicity of the vaccine will be assessed by standardized assays for antibody levels against AMA1-3D7 and AMA1-FVO, and an in vitro growth inhibition assay (GIA). The cellular basis of the immune responses will be evaluated by enumeration of relevant B and T cell subpopulations, including total and antigen-specific naive, memory and effector subpopulations specific for the antigens. The frequencies of B and T cells specific for the vaccine antigens in the group that received AMA1-C1/ Alhydrogel [R] will be compared to those in the group receiving Alhydrogel [R] alone. The total and antigen-specific cell frequencies in pre-immune (day 0) samples will serve as additional negative controls for the immunization. The goal of the study is to augment previously collected safety data for the 80 microgram antigen dose with a larger cohort, and to study the safety and immunogenicity of an accelerated vaccination schedule.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|