NCT00889616

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

Completed Phase 1 Last updated 17 December 2019

What this trial tests

Phase 1 trial testing BSAM2/Alhydrogel + CPG 7909 in Malaria in 154 participants. Completed in 18 July 2012.

Timeline

23 April 2009

18 July 2012

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	154
Start date	23 April 2009
Estimated completion	18 July 2012
Sites	2 locations across United States, Mali

Drugs / interventions tested

• BSAM2/Alhydrogel + CPG 7909 — full drug profile →

Conditions studied

• Malaria — all drugs for Malaria →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 50, any sex, with Malaria. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. CpG DNA as a vaccine adjuvant.
   Bode C, Zhao G, Steinhagen F, Kinjo T, et al · · 2011 · cited 648× · PMID 21506647 · DOI 10.1586/erv.10.174
2. Vaccine adjuvants: mechanisms and platforms.
   Zhao T, Cai Y, Jiang Y, He X, et al · · 2023 · cited 519× · PMID 37468460 · DOI 10.1038/s41392-023-01557-7
3. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer.
   Scheiermann J, Klinman DM. · · 2014 · cited 246× · PMID 24975812 · DOI 10.1016/j.vaccine.2014.06.065
4. Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases.
   Yang JX, Tseng JC, Yu GY, Luo Y, et al · · 2022 · cited 81× · PMID 35214155 · DOI 10.3390/pharmaceutics14020423
5. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.
   Ellis RD, Martin LB, Shaffer D, Long CA, et al · · 2010 · cited 67× · PMID 20107498 · DOI 10.1371/journal.pone.0008787
6. Phase 1 study in malaria naïve adults of BSAM2/Alhydrogel®+CPG 7909, a blood stage vaccine against P. falciparum malaria.
   Ellis RD, Wu Y, Martin LB, Shaffer D, et al · · 2012 · cited 47× · PMID 23056238 · DOI 10.1371/journal.pone.0046094
7. Blood stage vaccines for Plasmodium falciparum: current status and the way forward.
   Ellis RD, Sagara I, Doumbo O, Wu Y. · · 2010 · cited 45× · PMID 20519960 · DOI 10.4161/hv.6.8.11446
8. <i>Plasmodium falciparum</i> Malaria Vaccines and Vaccine Adjuvants.
   Bonam SR, Rénia L, Tadepalli G, Bayry J, et al · · 2021 · cited 29× · PMID 34696180 · DOI 10.3390/vaccines9101072