BK-SE36 phase 1a vaccine trial for falciparum malaria

ISRCTN ISRCTN78679862
DOI https://doi.org/10.1186/ISRCTN78679862
Secondary identifying numbers BK-SE36/001
Submission date
09/12/2009
Registration date
23/12/2009
Last edited
29/12/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Toshihiro Horii
Scientific

3-1 Yamadaoka
Suita, Osaka
565-0871
Japan

Study information

Study designPhase 1a single blind randomised placebo-controlled single centre trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleSingle-blind randomised controlled phase 1a trial of the safety and immunogenicity of lyophilised recombinant precipitated tropical malaria vaccine (BK-SE36) in Japan
Study objectivesAnnual 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(s)Institutional Review Board of the Research Foundation for Microbial Diseases of Osaka University approved on the 16th November 2004
Health condition(s) or problem(s) studiedFalciparum malaria
InterventionBK-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 typeDrug
Pharmaceutical study type(s)
PhasePhase I
Drug / device / biological / vaccine name(s)Tropical malaria vaccine (BK-SE36)
Primary outcome measureThe 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 measuresChanges 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 study start date14/01/2005
Completion date26/05/2005

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexMale
Target number of participants40
Total final enrolment40
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment14/01/2005
Date of final enrolment26/05/2005

Locations

Countries of recruitment

  • Japan

Study participating centre

3-1 Yamadaoka
Suita, Osaka
565-0871
Japan

Sponsor information

The Research Foundation for Microbial Diseases of Osaka University (BIKEN) (Japan)
Research organisation

3-1 Yamadaoka
Suita, Osaka
565-0871
Japan

Website http://www.biken.or.jp/english/index.html
ROR logo "ROR" https://ror.org/035t8zc32

Funders

Funder type

Government

Japanese Ministry of Education, Science, Sports, Culture and Technology (Japan) - Grant-in-Aid for Scientific Research on Priority Areas (ref: 13226058; 13225001)

No information available

The Research Foundation for Microbial Diseases of Osaka University (BIKEN) (Japan)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/09/2010 29/12/2020 Yes No

Editorial Notes

29/12/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.