Phase I Study of the Safety and Immunogenicity of BSAM-2/Alhydrogel +CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria in Adults in the US and Mali
Condition: Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  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 +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.

      Objectives:

        -  To assess safety and reactogenicity of the combination vaccine (BSAM-2/Alhydrogel +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.

      Eligibility:

        -  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.

      Design:

        -  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.
    

Detailed description: 
      This Phase I study will evaluate the blood stage P. falciparummalaria vaccine candidate
      BSAM-2/Alhydrogel +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 +500 (micro)g CPG 7909 at CIR,
      followed by another 15 who will receive 160 (micro)g BSAM-2/Altlhydrogel +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 +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.
    

Intervention name(s): BSAM2/Alhydrogel + CPG 7909
Intervention type(s): Drug
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria; Asexual Blood Stafe; Plasmodium Falciparum; Immunogenicity; Safety; Vaccine