Phase I Study of the Safety and Immunogenicity of BSAM-2/Alhydrogel(Registered Trademark)+CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria in Adults in the US and Mali
- Globally, the Plasmodium falciparum parasite is responsible for at least 247 million acute cases of malaria each year, resulting in about 1 million deaths. Approximately 90 percent of these deaths, the majority in children under 5 years of age, occur in Africa due to infection with P. falciparum.
- People living in endemic areas develop natural immunity to P. falciparum as a result of repeated infection. Consequently, children who survive to 5 years of age rarely succumb to life-threatening disease despite frequent infection. This acquired immunity is mediated in part by blood-stage parasite-specific antibodies. Thus, parasite proteins expressed during the blood-stage have been proposed as good candidates for inclusion in a vaccine.
- A number of P. falciparum merozoite antigens have been identified as promising blood-stage vaccine candidates, including Merozoite Surface Protein 1 (MSP 1) and Apical Membrane Antigen 1 (AMA 1). This Phase I study is the first time that the combination vaccine (BSAM-2/Alhydrogel(Registered Trademark)+CPG 7909) will be given to humans. The vaccine will be administered in a randomized, open-label (U.S.)/single-blinded (Mali), dose-escalating trial.
- To assess safety and reactogenicity of the combination vaccine (BSAM-2/Alhydrogel(Registered Trademark)+CPG 7909) in malaria-naive U.S. adults and semi-immune Malian adults.
- To determine the antibody response of the combination vaccine to the AMA 1 and MSP 142 proteins, as measured by antibody levels and parasite growth inhibition.
- To determine the extent to which the antibody response to the individual antigens (AMA 1 and MSP 142) is correlated when the combination vaccine is given, and to determine T and B cell responses to vaccination.
- United States: Healthy volunteers between 18 and 50 years, inclusive. Available for the 52 weeks of the trial and willing to participate in the study as evidenced by signing the informed consent document.
- Mali: Healthy volunteers between 18 and 45 years, inclusive, and a known resident of the village of Bancoumana. Available for the 52 weeks of the trial; willing to participate in the study as evidenced by signing the informed consent document or by fingerprinting the consent document with the signature of a witness.
- Potential participants must meet extensive health and screening requirements to participate in this study. Good general health is required as a result of review of medical history and clinical testing at the time of screening.
- Women who are pregnant or breastfeeding are not eligible.
During the 52-week study, participants will receive the first vaccine and complete the following:
- Physical examination and patient education regarding the signs and symptoms of potential adverse effects.
- Blood and urine testing, and vital signs (blood pressure, temperature, heart rate, and respiratory rate).
- United States: Education on the use of digital thermometer, injection-site reaction measurement, and malaria vaccine side-effect memory enhancement tool (daily symptom diaries).
- Mali: Additional blood draws for malaria smear and urine test for chloroquine testing.
- U.S. and Mali participants will return to the study site on specified days throughout the 52 weeks to receive two additional vaccines, record vital signs, complete additional blood and urine testing, and review patient education.
- U.S. participants will record oral temperature once during the day, as well as pain, tenderness, redness, swelling at the injection site and any systemic signs or symptoms for 6 days following each immunization.
- Participants will receive financial compensation (United States) or food (Mali) to compensate for their time.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Phase 1 Study of the Safety and Immunogenicity of BSAM-2/Alhydrogel(Registered Trademark)+CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria in Adults in the US and in Bancoumana, Mali|
- To assess safety and reactogenicity of BSAM-2/Alhydrogel + CPG 7909 in malaria-naive US adults and semi-immune Malian adults.
- To determine the antibody response of the combination vaccine to the AMA1-1 and MSP1(42) proteins, as measured by antibody levels and growth inhibition.
|Study Start Date:||April 2009|
|Study Completion Date:||July 2012|
Drug: BSAM2/Alhydrogel + CPG 7909
This Phase I study will evaluate the blood stage P. falciparummalaria vaccine candidate BSAM-2/Alhydrogel(Registered Trademark)+CPG 7909 in adults in the US and Mali. BSAM-2 contains a mixture of two proteins found on the surface of merozoites, AMA1 and MSP1(42). The study is open label, dose escalating in the US, and will be single-blinded and randomized with a comparator vaccine (Euvax B - Hepatitis B) in Mali. All volunteers will receive three doses of vaccine, given at 0, 2, and 6 months and administered in the deltoid muscle. The US arm of the study will be conducted at the Center for Immunization Research (CIR), in Washington DC. Fifteen (15) healthy volunteers will receive 40 (micro)g BSAM-2/Alhydrogel(Registered Trademark)+500 (micro)g CPG 7909 at CIR, followed by another 15 who will receive 160 (micro)g BSAM-2/Altlhydrogel(Registered Trademark)+500 (micro)g CPG 7909. Safety data to at least one week after the second vaccination from all US volunteers will be reviewed by a Safety Monitoring Committee prior to vaccinating volunteers in Mali. The highest safe dose will be administered in Mali after safety data in US adults have been reviewed by the SMC. The Mali arm of the study will be conducted in Bancoumana. Thirty (30) volunteers will be randomized to receive either BSAM 2/Alhydrogel(Registered Trademark)+CPG7909 or the licensed comparator vaccine. The primary objective of the study is to demonstrate safety and reactogenicity of the vaccine in both malaria naive and semi-immune adults. Secondary objectives are to determine the antibody response of the combination vaccine to the AMA1 and MSPl(42) proteins, as measured by antibody levels and parasite growth inhibition. Study endpoints are the incidence of local and systemic adverse events, antibody responses to AMA1 and MSP1(42) proteins, and in vitro growth inhibition of falciparum parasites. Exploratory immunologic analyses will also be conducted.
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21205|
|Malaria Research and Training Center|
|Principal Investigator:||Clifton E Barry, Ph.D.||National Institute of Allergy and Infectious Diseases (NIAID)|