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MalariaPhase 1NCT00889616

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

A Phase 1 study testing BSAM2/Alhydrogel + CPG 7909 in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Malaria
What is being tested?
BSAM2/Alhydrogel + CPG 7909
How many people
154 participants
Where
2 sitesin 2 countries
Study dates
23 Apr 2009to 18 Jul 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)

Who cannot join

  • 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).
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  • 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
  • Positive ELISA and confirmatory Western blot tests for HIV-1.
  • Positive ELISA and confirmatory tests for hepatitis C virus (HCV).
  • Positive hepatitis B surface antigen (HBsAg) by ELISA.
  • Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren s syndrome, or autoimmune thrombocytopenia.
  • Known immunodeficiency syndrome.
  • Positive serum anti-dsDNA titer.
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
  • Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
  • History of a surgical splenectomy.
  • Receipt of blood products within the past 6 months.
  • Previous receipt of an investigational malaria vaccine.
  • Receipt of antimalarial prophylaxis during the past 12 months, or receipt of chloroquine or related compounds (hydroxychloroquine, amodiaquine, or primaquine) in the 8 weeks prior to study entry.
  • Prior malaria infection by history.
  • Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives.
  • 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 (Beta-hCG test at any point during the study (if female).
  • If female, subject and her spouse have not used or are unwilling to use reliable contraceptive methods such as: abstinence, birth control pills or birth control patches or vaginal ring, diaphragm with spermicide, IUD (intrauterine device), condom with spermicide, progestin implant or injection, or surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) prior to enrollment to 3 months after the final vaccination. (At the time of vaccination, a female subject must have had a negative urine pregnancy test on 2 occasions at least 2 weeks apart, and must have used a reliable contraceptive method in the interim.)
  • Currently is lactating and breast-feeding (if female).
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, chronic infectious or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
  • Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol.
  • Pre-existing known autoimmune diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren s syndrome, autoimmune thrombocytopenia.
  • Laboratory evidence of possible autoimmune disease determined by anti-dsDNA titer that equals or exceeds 25 IU.
  • Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25 times the upper limit of normal of the testing laboratory).
  • Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory, or more than trace protein or blood on urine dipstick testing confirmed by repeat testing of clean-catch, midstream sample). (More than trace blood on urine dipstick will not exclude a female who is actively menstruating.)
  • Laboratory evidence of hematologic disease (absolute leukocyte count less than 3000/mm(3) or greater than 11,500/mm(3); hemoglobin less than 0.9 times the lower limit of normal of the testing laboratory, by gender; absolute granulocyte count less than 1300/mm(3); absolute lymphocyte count less than 1000/mm(3); or platelet count less than 110,000/mm(3).
  • Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
  • Participation in another investigational vaccine or drug trial within 30 days of starting this study, or while this study is ongoing.
  • Volunteer 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
  • Positive hepatitis B surface antigen (HBsAg). Hepatitis C antibody by rapid diagnostic test.
  • Known immunodeficiency syndrome.
  • Use of systemic corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
  • Receipt of a live vaccine within past 4 weeks or a non-live vaccine within past 2 weeks prior to entry into the study.
  • History of a surgical splenectomy.
  • Receipt of blood products within the past 6 months.
  • Previous receipt of an investigational malaria vaccine.
  • History of use of chloroquine or related compounds (hydroxychloroquine, amodiaquine, or primaquine) within 8 weeks of study entry.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Johns Hopkins University

    Baltimore, Maryland, 21205

Other trials in United States

Mali1 site

  • Malaria Research and Training Center

    Bamako

Other trials in Mali

About this study

Official title: Phase 1 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 in Bancoumana, Mali

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.
Read more

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.
Read the 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.

Conditions
Malaria
Being tested
BSAM2/Alhydrogel + CPG 7909
Keywords
Malaria, Asexual Blood Stafe, Plasmodium Falciparum, Immunogenicity, Safety, Vaccine
Medical subject headings
Malaria, Malaria, Falciparum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BSAM2/Alhydrogel + CPG 7909Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

  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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2009 (estimated)
  2. Study start23 Apr 2009
  3. Study completion18 Jul 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
154 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00889616
Sponsor's protocol ID
999909134
Other IDs
09-I-N134
Status last verified
18 Jul 2012
First submitted
28 Apr 2009
Last updated
17 Dec 2019
Results posted
No

Publications

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

    PubMed 11832956

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

    PubMed 11832958

  • 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.

    PubMed 12228305

  • 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.

    PubMed 23056238

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BSAM2/Alhydrogel + CPG 7909 in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Mali. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess safety and reactogenicity of BSAM-2/Alhydrogel + CPG 7909 in malaria-naive US adults and semi-immune Malian adults.. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00889616, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.

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