Phase I Study of AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909 Malaria Vaccine
This study will evaluate the safety and immune response of healthy volunteers to an experimental malaria vaccine called AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909. Malaria is an infection of red blood cells caused by a parasite, Plasmodium falciparum, that is spread by certain kinds of mosquitoes. Each year, about 1 million people are killed by malaria worldwide, most of them young children in Africa. AMA1 C1 may help block the malaria parasite from getting into red blood cells. The vaccine is mixed with Alhydrogel® (Registered Trademark), a material that is commonly added to vaccines to make them work better (also called an adjuvant). Besides evaluating the vaccine, this study will also test two solutions of an experimental adjuvant, CPG 7909-P and CPG 7909-S.
Healthy people between 18 and 50 years of age may be eligible for this 7-month study. Participants are randomly assigned to one of four treatment groups (A, B, C or D below). All receive two vaccinations, given as a shot in the upper arm either 1 or 2 months apart, as shown:
- Group A: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-P at Day 0 and Day 28 (1-month interval)
- Group B: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-S at Day 0 and Day 28 (1-month interval)
- Group C: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-P at Day 0 and Day 56 (2-month interval)
- Group D: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-S at Day 0 and Day 56 (2-month interval)
Group A and B participants return to the clinic for checkups at 3, 7, and 14 days after each vaccination and again at months 2, 3, 4, 5, and 7. Group C and D participants come to the clinic at 3, 7, and 14 days after each vaccination and again at months 3, 4, 5, and 7.
In addition to the vaccinations, the study includes the following procedures:
- Photographs of the subject's arm where the vaccination is given if a rash develops.
- Daily temperature and symptoms record for the first 6 days after each of the 2 vaccinations, and at any other time there is concern about fever or other symptoms.
- Blood draws about 12 times during the study to check for safety and to measure the antibody response and the effect of the study vaccine.
Some participants may be asked to undergo plasmapheresis, a procedure for collecting plasma, the liquid part of the blood. This is done by using a machine called a blood cell separator. Blood is collected through a needle place...
Biological: AMA1-C1/Alhydrogel + CPG 7909 (Saline)
Biological: AMA1-C1/Alhydrogel + CPG 7909 (Phosphate)
Drug: AMA1-C1/Alhydrogel + CPG 7909
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Primary Purpose: Prevention
|Official Title:||Phase I Study of the Safety and Immunogenicity of AMA1-C1/Alhydrogel + CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria|
- Assessment of the safety and reactogenicity of the AMA1-C1/Alhydrogel + CPG 7909 vaccine in phosphate and saline buffers; and determine the frequency of summarized systemic and local AFs by severity and relationship to the vaccine.
- Demonstrate that the immune responses to AMA1-C1 7909 in a saline buffer are not inferior to the immune responses to AMA-C1 + CPG 7909 in a phosphate buffer.
|Study Start Date:||January 2007|
|Study Completion Date:||November 2008|
|Primary Completion Date:||November 2008 (Final data collection date for primary outcome measure)|
Biological: AMA1-C1/Alhydrogel + CPG 7909 (Saline)
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.
|United States, District of Columbia|
|Johns Hopkins University Bloomberg School of Public Health|
|Washington, District of Columbia, United States, 20037|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|