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

NCT00889616 | Completed Phase 1

• 2 other identifiers: 99990913409-I-N134
• Study Type: interventional
• Target: 154
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Malaria

Keywords

Malaria; Asexual Blood Stafe; Plasmodium Falciparum; Immunogenicity; Safety; Vaccine

Outcome Measures

Primary Outcomes (1)

• To assess safety and reactogenicity of BSAM-2/Alhydrogel + CPG 7909 in malaria-naive US adults and semi-immune Malian adults.

Secondary Outcomes (1)

• 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.

Interventions

BSAM2/Alhydrogel + CPG 7909 DRUG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• All of the following criteria must be fulfilled for a volunteer to participate in this trial:
• Age between 18 and 50 years (US) or 18 and 45 years (Mali), inclusive
• Good general health as a result of review of medical history and/or clinical testing at the time of screening
• Available for the duration of the trial (52 weeks in the U.S. and 104 weeks in Mali)
• Willingness 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 (Mali)
• Known resident of the village of Bancoumana (Mali)

You may not qualify if:

• A volunteer will be excluded from participating in this trial if any one of the following criteria is fulfilled:
• Pregnancy as determined by a positive urine or serum test at any point during the study for human choriogonadotropin (Beta-hCG) (if female).
• Subject is unwilling to use reliable contraception methods for the period of at least 2 months prior to first vaccination to 3 months after last vaccination (if female). Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female).
• Currently is lactating and breast-feeding (if female).
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol.
• Neutropenia as defined by an absolute neutrophil count less than 1500/mm(3).
• Alanine transaminase (ALT) level above the laboratory-defined upper limit of normal.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
• Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the subject unable to comply with the protocol.
• History of receiving any investigational product within the past 30 days.
• Participant has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
• History of a severe allergic reaction or anaphylaxis.
• Severe asthma. This will be defined as:
• Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past 2 years, or that requires the use of oral or parenteral corticosteroids
• Clinically significant reactive airway disease that does not respond to bronchodilators

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Malaria Research and Training Center

Bamako, Mali

Location

Related Publications (4)

• Sachs J, Malaney P. The economic and social burden of malaria. Nature. 2002 Feb 7;415(6872):680-5. doi: 10.1038/415680a.

  PMID: 11832956 BACKGROUND

• Richie TL, Saul A. Progress and challenges for malaria vaccines. Nature. 2002 Feb 7;415(6872):694-701. doi: 10.1038/415694a.

  PMID: 11832958 BACKGROUND

• Healer J, Crawford S, Ralph S, McFadden G, Cowman AF. Independent translocation of two micronemal proteins in developing Plasmodium falciparum merozoites. Infect Immun. 2002 Oct;70(10):5751-8. doi: 10.1128/IAI.70.10.5751-5758.2002.

  PMID: 12228305 BACKGROUND

• Ellis RD, Wu Y, Martin LB, Shaffer D, Miura K, Aebig J, Orcutt A, Rausch K, Zhu D, Mogensen A, Fay MP, Narum DL, Long C, Miller L, Durbin AP. Phase 1 study in malaria naive adults of BSAM2/Alhydrogel(R)+CPG 7909, a blood stage vaccine against P. falciparum malaria. PLoS One. 2012;7(10):e46094. doi: 10.1371/journal.pone.0046094. Epub 2012 Oct 4.

  PMID: 23056238 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Aluminum Hydroxide; ProMune

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes

Study Officials

• Ruth D Ellis, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 28, 2009
• First Posted: April 29, 2009
• Study Start: April 23, 2009
• Study Completion: July 18, 2012
• Last Updated: December 17, 2019

Record last verified: 2012-07-18

Locations

US (1); MA (1)