BK-SE36 phase 1a vaccine trial for falciparum malaria
| ISRCTN | ISRCTN78679862 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78679862 |
| Protocol serial number | BK-SE36/001 |
| Sponsor | The Research Foundation for Microbial Diseases of Osaka University (BIKEN) (Japan) |
| Funders | Japanese Ministry of Education, Science, Sports, Culture and Technology (Japan) - Grant-in-Aid for Scientific Research on Priority Areas (ref: 13226058; 13225001), The Research Foundation for Microbial Diseases of Osaka University (BIKEN) (Japan) |
- 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
Scientific
3-1 Yamadaoka
Suita, Osaka
565-0871
Japan
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Phase 1a single blind randomised placebo-controlled single centre trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| 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 |
| Study objectives | 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(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) studied | 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 / device / biological / vaccine name(s) | Tropical malaria vaccine (BK-SE36) |
| Primary outcome measure(s) |
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. |
| Key secondary outcome measure(s) |
Changes in the anti-SE36 protein antibody titre at each time point. |
| Completion date | 26/05/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Male |
| Target sample size at registration | 40 |
| Total final enrolment | 40 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 14/01/2005 |
| Date of final enrolment | 26/05/2005 |
Locations
Countries of recruitment
- Japan
Study participating centre
3-1 Yamadaoka
Suita, Osaka
565-0871
Japan
565-0871
Japan
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not 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 |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
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.
