Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
BK-SE36/001
Study information
Scientific title
Single-blind randomised controlled phase 1a trial of the safety and immunogenicity of lyophilised recombinant precipitated tropical malaria vaccine (BK-SE36) in Japan
Acronym
Study hypothesis
Annual outbreaks of highly fatal falciparum malaria affect 500 million people worldwide, mainly in the tropical and subtropical regions, resulting in 1 - 3 million deaths. In Japan, malaria is brought by persons who travel abroad and foreigners visiting Japan, with a few fatal cases of falciparum malaria sporadically reported. Drug-resistant Plasmodium has recently become prevalent, and expansion of the epidemic region due to global warming is a matter of concern, for which development of malaria vaccine is expected as a drastic measure. However, the outlook for practical application is still not in sight despite huge research efforts being made worldwide. Recombinant SE36 protein based on the N-terminal domain of P. falciparum serine repeat antigen (SERA) is a promising vaccine candidate. GMP grade of SE36 protein (BK-SE36) was prepared by extraction and purification of recombinant SE36 protein expressed in Escherichia coli, followed by adsorption to aluminum hydroxide and freeze-drying. The vaccine passed various specification tests, and was confirmed to be safe in GLP-conforming non-clinical studies (single- and repeated-dose toxicity studies, genotoxicity test, safety pharmacology, mutagenesis and local irritability test). Moreover, BK-SE36 cause no clinical symptom or abnormalities in haematology or blood chemistry, and induced marked antibody production against SE36 protein in immunological studies in chimpanzees. The design and choice of trial population for this first-in-man clinical phase 1 trial is based on the need to initially demonstrate the safety of BK-SE36 in humans.
Ethics approval
Institutional Review Board of the Research Foundation for Microbial Diseases of Osaka University approved on the 16th November 2004
Study design
Phase 1a single blind randomised placebo-controlled single centre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Falciparum malaria
Intervention
BK-SE36 versus placebo, subcutaneously, three times a day at 21 day interval. Dosage is as follows:
Group 1: each administration contains half dose of BK-SE36 (0.5 ml)
Group 2: each administration contains full dose of BK-SE36 (1.0 ml)
The total duration of follow-up is 63 days.
Intervention type
Drug
Phase
Phase I
Drug names
Tropical malaria vaccine (BK-SE36)
Primary outcome measure
The safety of BK-SE36 is assessed by the presence or absence of adverse events evaluated from test results, subjective/objective symptoms, laboratory data, blood pressure/pulse rate and body temperature.
Subjects were visited once a week. At every subjects' visit to the hospital, doctors did health interview for finding some symptoms and blood/serum examination and measurement of blood pressure etc were conducted at the time.
Secondary outcome measures
Changes in the anti-SE36 protein antibody titre at each time point.
Subjects were visited once a week. At every subjects' visit to the hospital, doctors did health interview for finding some symptoms and blood/serum examination and measurement of blood pressure etc were conducted at the time.
Overall trial start date
14/01/2005
Overall trial end date
26/05/2005
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Healthy adult Japanese males aged 20 to 35 years (age on informed consent)
2. Those whose body mass index (BMI) is 18.5 to 25.0 kg/m^2
3. Those who are able to agree, comply with matters to be observed during participation in the trial, undergo consultation/examination, as described in this protocol, and report symptoms
4. Those who are considered to be eligible to participate in this trial based on screening:
4.1. Vital signs and physical examination are within baseline range
4.2. Haematology: within 15% deviations from the upper and lower limits of the baseline range. The differential white blood count is not questioned when the white blood cell count is within the baseline range.
4.3. Blood chemistry:
4.3.1. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine within the baseline range
4.3.2. Total bilirubin, triglyceride (TG) within 50% deviation from the upper limit
4.3.3. Serum electrolytes within the baseline range
4.3.4. Other blood chemistry items within 15% deviation from the upper and lower limits of the baseline range
4.4. Urinalysis within the normal range
4.5. Infectious disease tests within the normal ranges
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
40
Participant exclusion criteria
1. Persons with fever (37.5°C or higher) on administration of the test vaccine
2. Persons with clear symptoms of serious acute disorders
3. Persons with a clear history of food/drug-related anaphylaxis
4. Persons with a clear history of malaria, or those with anti-plasmodium falciparum (SE36 antigen) antibody
5. Persons with a history or present illness of disorders requiring gastrointestinal surgery, serious cardiovascular/blood system/respiratory/liver/kidney/digestive tract/neuropsychiatric disorders, or developmental anomalies
6. Persons with a history of fever within 2 days after preventive administration with other types of vaccine, or those in whom symptoms have suggested systemic allergy
7. Persons with a history of convulsion
8. Persons under a diagnosis of immunodeficiency
9. Persons with a history or tentative diagnosis of drug allergy
10. Persons with a history of or present drug/ alcohol dependency
11. Persons who took any medication within 1 week before administration of this test vaccine
12. Persons to whom any live vaccine was administered within 4 weeks before administration of this test vaccine, or inactivated vaccine/toxoid was administered within 1 week
13. Persons who participated in another trial within 4 months before administration of this test vaccine
14. Persons in whom 200 ml of blood was collected (donation) within 1 month before administration of this test vaccine, or more than 400 ml of blood was collected within 3 months
15. Persons consuming excessive alcohol or cigarettes
16. Persons with a positive reaction on drug abuse screening
17. Others who are not considered to be eligible by the chief principal investigator or sub-investigator
Recruitment start date
14/01/2005
Recruitment end date
26/05/2005
Locations
Countries of recruitment
Japan
Trial participating centre
3-1 Yamadaoka
Suita, Osaka
565-0871
Japan
Sponsor information
Organisation
The Research Foundation for Microbial Diseases of Osaka University (BIKEN) (Japan)
Sponsor details
3-1 Yamadaoka
Suita
Osaka
565-0871
Japan
Sponsor type
Research organisation
Website
Funders
Funder type
Government
Funder name
Japanese Ministry of Education, Science, Sports, Culture and Technology (Japan) - Grant-in-Aid for Scientific Research on Priority Areas (ref: 13226058; 13225001)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Research Foundation for Microbial Diseases of Osaka University (BIKEN) (Japan)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list