Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201701001921166 Date of Approval: 16/12/2016
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Safety and Immunogenicity of the Malaria Vaccine Candidate BK-SE36/CpG in Healthy Malaria-Exposed African Adults and Children Living in Burkina Faso
Official scientific title Age de-escalation study to assess safety and immunogenicity of recombinant E. coli BK-SE36 malaria vaccine candidate formulated with CpG adjuvant administered intramuscularly in healthy malaria exposed African adults and children living in Burkina Faso.
Brief summary describing the background and objectives of the trial The malaria vaccine candidate BK-SE36 is based on a recombinant form of the Plasmodium falciparum serine repeat antigen (SERA). The vaccine candidate was selected for clinical development on the following basis: (i)epidemiological studies showing high antibody titers that inversely correlate with malaria symptoms and severe disease; (ii) in vitro studies demonstrating induction of antibodies that are inhibitors of parasite growth, exert antibody-dependent complement-mediated lysis of schizonts, or antibody-dependent monocyte-mediated parasite growth inhibition; and (iii) animal studies demonstrating protection against P. falciparum challenge in non-human primates. The safety and immunogenicity of BK-SE36 was demonstrated in a phase Ia trial in malaria naive Japanese adults; and in a phase Ib trial conducted in healthy subjects aged 6-32 years from a malaria endemic area in Northern Uganda.The trial promising results justified the conduct of a phase Ib trial of BK-SE36 in younger cohorts aged from 1 - 5 years old toddlers in Burkina Faso. This on-going trial aims at testing the immune response in younger cohorts that has so far not been included in BK-SE36 malaria vaccine clinical trial, compare clinical trial results from two African countries with different malaria endemicity and generate additional data on safety, immunogenicity and possible preliminary efficacy of BK-SE36.The immune response to BK-SE36 may still be improved with the use of DNA sequences containing CpG motifs that can selectively promote cellular and/or humoral immune responses. A phase Ia clinical trial using BK-SE36/CpG was conducted in healthy adults in Japan where the vaccine was deemed safe and elicited antibody titres were 3- to 4- fold higher as compared to BK-SE36 alone. The proposed clinical trial will assess BK-SE36/CpG safety and immunogenicity in a population exposed to malaria.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 30/09/2017
Actual trial start date 23/05/2018
Anticipated date of last follow up 30/04/2019
Actual Last follow-up date 27/04/2020
Anticipated target sample size (number of participants) 135
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
NPC-SE36/001 Sponsor protocol number
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomisation (variable block size, random mixture of block size of 6 and 9) Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Adults aged 21 to 45 years 100¿g SE36/1mg Aluminium hydroxide/1mg CpG-ODN K3 3 times Week 0, 4 and 16 100¿g SE36/1mg Aluminium hydroxide/1mg CpG-ODN K3 will be given by intramuscular route to adults aged 21-45 years 30
Experimental Group Childre aged 5 to 10 years old 100¿g SE36/1mg Aluminium hydroxide/1mg CpG-ODN K3 3 times Week 0, 4 and 16 100¿g SE36/1mg Aluminium hydroxide/1mg CpG-ODN K3 will be given by intramuscular route to children aged 5-10years 30
Experimental Group Children aged 12 to 24 months 100¿g SE36/1mg Aluminium hydroxide/1mg CpG-ODN K3 3 times Week 0, 4 and 16 100¿g SE36/1mg Aluminium hydroxide/1mg CpG-ODN K3 will be given by intramuscular route to children aged 12 to 24 months 30
Control Group commercial rabies vaccine children 5 to 10 years 1 dose 3 times Week 0, 4 and 16 commercial rabies vaccine will be given by intramuscular route to children aged 5-10 years 15 Active-Treatment of Control Group
Control Group commercial rabies vaccine adults 21-45 years 1 dose 3 times Week 0, 4 and 16 commercial rabies vaccine will be given by intramuscular route to adults aged 21-45 years 15 Active-Treatment of Control Group
Control Group commercial rabies vaccine children aged 12 to 24 months 1 dose 3 times Week 0, 4 and 16 commercial rabies vaccine will be given by intramuscular route to children aged 12 to 24 months 15 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Specific inclusion criteria for cohort 1 (adults 21-45 years old) ¿ Female or male subjects aged 21 to 45 years inclusive at the time of the first vaccination ¿ Residing within the Ouagadougou health region and planning to stay for the study duration ¿ General good health based on medical history and clinical examination ¿ Written informed consent obtained before any trial procedure ¿ Female and male volunteers practicing /willing to practice contraceptive methods recommended by the national health system for at least four (4) weeks before the first vaccination (for female participants only) and up to four (4) weeks after the third vaccination. Specific inclusion criteria for cohort 2 (children 5-10 years old) ¿ Female or male subjects aged 5 to 10 years inclusive at the time of first vaccination. Specific inclusion criteria for cohort 3 (children 12-24 months) ¿ Female or male subjects aged 12 to 24 months inclusive at the time of first vaccination. Common inclusion criteria for cohorts 2 and 3 ¿ Residing within the Ouagadougou health region and planning to stay for the study duration ¿ Appear to be in generally good health based on malnutrition index and clinical and laboratory investigations ¿ Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are not literate, the consent form will be countersigned by an impartial witness ¿ Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) will be enrolled in the study. The trial period for each subject is 14 months (12 months + 8 weeks screening). Specific non-inclusion criteria for cohort 1 ¿ Positive pregnancy test ¿ Currently breastfeeding ¿ Suspected or current known alcohol or drug abuse Specific non-inclusion criteria for cohort 3 ¿ Weight-for-age Z score of less than ¿3 or other relevant clinical signs of malnutrition For cohort 1, 2 and 3 ¿ Previous participation in any malaria vaccine trial ¿ History of blood transfusion within the last 3 months ¿ Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the volunteers ¿ Any clinically significant laboratory abnormalities on screened blood samples outside the normal range, as defined at the clinical trial site. Specifically: o Haemoglobin less than 8.0 g/dL, o Serum Creatinine concentration greater than 70 µmol/L, o Serum ALT concentration greater than 45 U/L, o Low platelet count (< 100,000/mm3) ¿ Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior to recruitment. (For corticosteroids, this will mean prednisone, or equivalent, ¿ 0.5 mg/kg/day. Inhaled and topical steroids are allowed.) ¿ Any confirmed or suspected immunosuppressive or immunodeficiency condition based on medical history and physical examination (No testing will be done for HIV) ¿ A family history of congenital or hereditary immunodeficiency ¿ History of auto immune disease ¿ Major congenital defects ¿ Subjects with splenectomy ¿ History of anaphylaxis or known severe hypersensitivity to any of the vaccine components (adjuvant or antigen or excipient) ¿ Administration of gamma globulin: 4 weeks prior to and after each vaccination; if administration is necessary during the study period, the volunteer will be withdrawn from the study ¿ Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s) ¿ Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period ¿ Current participation in another clinical trial, or within 12 weeks of this study ¿ Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial or result in incomplete or poor quality data. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s) 12 Month(s) 45 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 20/09/2017 Osaka University Research Ethical Review Board
Ethics Committee Address
Street address City Postal code Country
Not available Osaka 0000000 Japan
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 05/09/2017 London School of Hygiene and Tropical Medicine Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Keppel street London 000000 United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/11/2017 Comite d ethique pour la recherche en sante
Ethics Committee Address
Street address City Postal code Country
Not available Ouagadougou 03000 Burkina Faso
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Assess the safety and reactogenicity of 3 doses of malaria vaccine candidate BK-SE36 mixed with CpG K3 ODN via the intramuscular route, in healthy African adults and children exposed to the parasite P. falciparum.The primary objective is restricted to serious or severe adverse events. ¿ Occurrence of solicited adverse events considered related to vaccination and that are severe within 7 days following vaccination ¿ Occurrence of unsolicited adverse events considered related to vaccination and that are severe (Grade 3) within 28 days following each vaccination ¿ Occurrence of serious adverse events at any point during the study period
Secondary Outcome ¿ Assess the humoral immune response to the vaccine antigens administered intramuscularly by measuring the level of IgG in all subjects ¿ Assess the safety and reactogenicity of the BK-SE36/CpG vaccine restricted to mild or moderate adverse events. ¿ Anti-SE36 protein IgG antibody titre at Day 0, Week 4, 8, 16, 20 and 52. ¿ Occurrence of solicited and unsolicited mild or moderate adverse events as done for the primary outcome
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Institue de Recherche en Sciences de la Sante IRSS 03 BP 7192 Ouagadougou 003000 Burkina Faso
FUNDING SOURCES
Name of source Street address City Postal code Country
Global Health Innovative Technology Fund Ark Hills Sengokuyama Mori Tower 25F, 1-9-10 Roppongi, Minato-ku, Tokyo 106-0032 Japan
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Nobelpharma Co., Ltd Kyodo Bldg. (Horidome) 12-10 Nihonbashikobunacho, Chuo-Ku Tokyo 103-0024 Japan Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Institut de Recherche en Sciences de la Sante IRSS 03 BP 7192 Ouagadougou 03000 Burkina Faso
Research Institute for Microbial Diseases (RIMD) Osaka University 3-1 Yamadaoka, Suita Osaka 565-0871 Japan
European Vaccine Initiative UniversitätsKlinikum Heidelberg Vossstrasse 2, Geb. 4040 Heidelberg 69115 Germany
London School of Hygiene & Tropical Medicine Keppel street London WC1E 7HT United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Sodiomon Sirima gras@fasinet.bf +26676200444 Groupe de Recherche Action en Sante, GRAS, 06BP 10248
City Postal code Country Position/Affiliation
Ouagadougou 060000 Burkina Faso Principal investigator
Role Name Email Phone Street address
Public Enquiries Sophie Houard sophie.houard@euvaccine.eu +32 2 372 31 91 UniversitätsKlinikum Heidelberg Vossstrasse 2, Geb. 4040
City Postal code Country Position/Affiliation
Heidelberg 69115 Germany Vaccine development leader at EVI
Role Name Email Phone Street address
Scientific Enquiries Toshihiro Horii horii@biken.osaka-u.ac.jp +81(6)- 6879-8280 Osaka University 3-1 Yamadaoka, Suita
City Postal code Country Position/Affiliation
Osaka 565-0871 Japan Head of the Department of Molecular Protozoology at Osaka University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial phase 04/07/2018 Pactr update Not Applicable
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Purpose of the trial 04/07/2018 pactr update Prevention Prevention: Vaccines
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 10/08/2017 Updated timelines 2017-06-30 2017-09-30
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 10/08/2017 updated timelines 2017-06-30 2017-09-30
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 11/12/2018 update 23 May 2018
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 10/08/2017 Updated timelines 2018-07-31 2019-04-30
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 10/08/2017 updated timelines 2018-07-31 2019-04-30
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 11/12/2018 update 31 Jan 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 06/05/2021 Updated date provided by researcher 31 Jan 2020 27 Apr 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 11/12/2018 update Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 06/05/2021 Updated details provided by researcher Recruiting Closed to recruitment,follow-up continuing
Section Name Field Name Date Reason Old Value Updated Value
Study Design Allocation sequence 13/02/2017 typo correction Permuted block randomisation (variable block size, random mixture of block size of 6 and 8) Permuted block randomisation (variable block size, random mixture of block size of 6 and 9)
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 11/12/2018 Trial site had changed from Banfora to ouagadougou Specific inclusion criteria for cohort 1 (adults 21-45 years old) ¿ Female or male subjects aged 21 to 45 years inclusive at the time of the first vaccination ¿ Residing within the Banfora health district and planning to stay for the study duration ¿ General good health based on medical history and clinical examination ¿ Written informed consent obtained before any trial procedure ¿ Female and male volunteers practicing /willing to practice contraceptive methods recommended by the national health system for at least four (4) weeks before the first vaccination (for female participants only) and up to four (4) weeks after the third vaccination. Specific inclusion criteria for cohort 2 (children 5-10 years old) ¿ Female or male subjects aged 5 to 10 years inclusive at the time of first vaccination. Specific inclusion criteria for cohort 3 (children 12-24 months) ¿ Female or male subjects aged 12 to 24 months inclusive at the time of first vaccination. Common inclusion criteria for cohorts 2 and 3 ¿ Residing within the Banfora health district and planning to stay for the study duration ¿ Appear to be in generally good health based on malnutrition index and clinical and laboratory investigations ¿ Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are not literate, the consent form will be countersigned by an impartial witness ¿ Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) will be enrolled in the study. The trial period for each subject is 14 months (12 months + 8 weeks screening). Specific inclusion criteria for cohort 1 (adults 21-45 years old) ¿ Female or male subjects aged 21 to 45 years inclusive at the time of the first vaccination ¿ Residing within the Ouagadougou health region and planning to stay for the study duration ¿ General good health based on medical history and clinical examination ¿ Written informed consent obtained before any trial procedure ¿ Female and male volunteers practicing /willing to practice contraceptive methods recommended by the national health system for at least four (4) weeks before the first vaccination (for female participants only) and up to four (4) weeks after the third vaccination. Specific inclusion criteria for cohort 2 (children 5-10 years old) ¿ Female or male subjects aged 5 to 10 years inclusive at the time of first vaccination. Specific inclusion criteria for cohort 3 (children 12-24 months) ¿ Female or male subjects aged 12 to 24 months inclusive at the time of first vaccination. Common inclusion criteria for cohorts 2 and 3 ¿ Residing within the Ouagadougou health region and planning to stay for the study duration ¿ Appear to be in generally good health based on malnutrition index and clinical and laboratory investigations ¿ Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are not literate, the consent form will be countersigned by an impartial witness ¿ Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) will be enrolled in the study. The trial period for each subject is 14 months (12 months + 8 weeks screening).
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 11/12/2018 update Child: 6 Year-12 Year, Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s)
Section Name Field Name Date Reason Old Value Updated Value
Ethics CommitteeName 09/01/2017 new information IssuingAuthority IssuingAuthority
Section Name Field Name Date Reason Old Value Updated Value
Ethics CommitteeName 09/01/2017 new information IssuingAuthority IssuingAuthority
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 09/01/2017 new information SECONDARY_ID SECONDARY_ID
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 09/01/2017 new information SECONDARY_ID SECONDARY_ID
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 11/12/2018 Change of trial centre Centre National de Recherche et de Formation sur le Paludisme (CNRFP) Unité de Recherche clinique de Banfora (CNRFP/URC-B), 01 BP 2208, Ouagadougou, 01, Burkina Faso Institue de Recherche en Sciences de la Sante IRSS, 03 BP 7192, Ouagadougou, 003000, Burkina Faso
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/12/2018 Protocol was amended to reflect new trial site TRUE, Osaka University Research Ethical Review Board, , Osaka, , Japan, , 24 Mar 2017, , , TRUE, Osaka University Research Ethical Review Board, Not available, Osaka, 0000000, Japan, , 20 Sep 2017, +8166878346, secretar@biken-osaka-u.ac.jp,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/12/2018 ethics approval received TRUE, Osaka University Research Ethical Review Board, Not available, Osaka, 0000000, Japan, , 20 Sep 2017, +8166878346, secretar@biken-osaka-u.ac.jp, TRUE, Osaka University Research Ethical Review Board, Not available, Osaka, 0000000, Japan, , 20 Sep 2017, +8166878346, secretar@biken-osaka-u.ac.jp, 1921_2020_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/12/2018 Protocol was amended to reflect new trial site TRUE, London School of Hygiene & Tropical Medicine Research Ethics Committee, Keppel street, London, WC1E 7HT, United Kingdom, , 28 Apr 2017, , , TRUE, London School of Hygiene and Tropical Medicine Research Ethics Committee, Keppel street, London, 000000, United Kingdom, , 05 Sep 2017, +442076378636, Ethics@lshtm.ac.uk, 1921_2021_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/12/2018 Amended protocol was submitted to reflect new trial site TRUE, Comité d'éthique pour la recherche en santé, , Ouagadougou, , Burkina Faso, , 22 Feb 2017, , , TRUE, Comite d ethique pour la recherche en sante, Not available, Ouagadougou, 03000, Burkina Faso, , 08 Nov 2017, +22670261462, sophie.houard@euvaccine.eu,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/12/2018 ethics letter received TRUE, Comite d ethique pour la recherche en sante, Not available, Ouagadougou, 03000, Burkina Faso, , 08 Nov 2017, +22670261462, sophie.houard@euvaccine.eu, TRUE, Comite d ethique pour la recherche en sante, Not available, Ouagadougou, 03000, Burkina Faso, , 08 Nov 2017, +22670261462, sophie.houard@euvaccine.eu, 1921_2022_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 11/12/2018 Trial site collaborators has been changed Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 1487 Avenue Kumda Yonré, Ouagadougou, 01, Burkina Faso Institut de Recherche en Sciences de la Sante IRSS, 03 BP 7192, Ouagadougou, 03000, Burkina Faso
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 11/12/2018 New email and address Principal Investigator, Sodiomon, Sirima, Dr., s.sirima.cnlp@fasonet.bf, , +226 702 004 44, 1487 Avenue Kumda Yonré, Ouagadougou, 01, Burkina Faso, Principal investigator Principal Investigator, Sodiomon, Sirima, Dr., gras@fasinet.bf, sodiomon@yahoo.fr, +26676200444, Groupe de Recherche Action en Sante, GRAS, 06BP 10248, Ouagadougou, 060000, Burkina Faso, Principal investigator