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.: PACTR202010819218562 Date of Registration: 01/10/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title OEV128 Gambia ETVAX Efficacy Trial (GEET)
Official scientific title An individually-randomized, double-blind, placebo-controlled phase 2b trial (OEV-128) examining the efficacy of oral inactivated ETVAX vaccine to prevent enterotoxigenic E. coli-associated diarrhoea in Gambian children ages 6 to 18 months.
Brief summary describing the background and objectives of the trial The global diarrhoeal disease burden remains high, with approximately four billion cases estimated to occur annually in all age groups, with the highest incidence among infants and young children under five years of age (6 months – 5 years). In this age group, enteric infections result in nearly 600,000 deaths each year, comprising approximately 9 percent of global infant mortality and an enormous physical and economic toll in low resource countries. Diarrhoea is second to pneumonia among the leading causes of death due to disease in children under five years old in low and/or Middle Income Countries (LMIC), and can also be a triggering event for death from other causes, particularly pneumonia. Among the primary infectious causes of diarrhoeal disease, enterotoxigenic E. coli (ETEC) is one of the most important pathogens for which there is currently no licensed vaccine. ETEC has been a long-standing World Health Organization (WHO) target for vaccine development. In The Gambia, diarrhoea accounts for about 9% of deaths among children under five years old. The objectives of this study are to evaluate the safety and protective efficacy of ETVAX®, an inactivated whole cell vaccine candidate, administered to children 6-18 months of age. Data suggesting that ETVAX is safe and efficacious may influence global, regional, and national policy makers to consider advancing this vaccine to routine use among young children in low and middle-income nations. The widespread use of this vaccine may reduce diarrhoea cases in the under 5-age population and ultimately reduce under 5-age mortality.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) OEV128
Disease(s) or condition(s) being studied Digestive System
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 11/01/2021
Actual trial start date 22/02/2021
Anticipated date of last follow up 01/03/2023
Actual Last follow-up date 31/10/2023
Anticipated target sample size (number of participants) 4936
Actual target sample size (number of participants) 4936
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
MCA ref No 17868 MCA The Gambia
17868 LSHTM Ethics
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 randomization Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Sodium Bicarbonate Buffer A total of 3 doses will be administered to each participant, 10.84 ml per dose (10 ml buffer + 0,84 ml water). Dose will be given at study day 1, 15 and 90. 90 days vaccination period This is a randomized, double-blind, placebo-controlled paediatric phase 2b trial testing the efficacy of ETVAX, an oral, inactivated, whole-cell and dmLT adjuvanted ETEC vaccine. A total of 4936 healthy children ages 6-18 months, 2468 each in the vaccine or placebo group, will be enrolled. At the clinic, eligible children will be randomized to receive vaccine or placebo with 1:1 allocation. The parents will be requested to bring the child for a second dose on trial day 15, and again for a third dose on day 90 (3 months after the first dose). 2468 Placebo
Experimental Group ETVAX Each participant will receive 3 doses in total, 10.84 ml per dose (10 ml buffer + 0.825 ml ETVAX®+0.0125ml dmLT). Dose will be administered at study day 1, 15 and 90. 90 days vaccination period This is a randomized, double-blind, placebo-controlled paediatric phase 2b trial testing the efficacy of ETVAX, an oral, inactivated, whole-cell and dmLT adjuvanted ETEC vaccine. A total of 4936 healthy children ages 6-18 months, 2468 each in the vaccine or placebo group, will be enrolled. At the clinic, eligible children will be randomized to receive vaccine or placebo with 1:1 allocation. The parents will be requested to bring the child for a second dose on trial day 15, and again for a third dose on day 90 (3 months after the first dose). 2468
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Healthy children 6 to 18 months old at the time of enrolment. 2. Generally good health over the 7 days before enrolment and the day of 1st dose of vaccine/placebo. 3. Parent properly informed about the study, able to understand it and sign or thumb print the informed consent form. 4. Parent and child available for the entire study period of the study and reachable by study staff throughout the entire follow-up period. 1. Presence of any significant known systemic disorder as determined by medical history and/or physical examination which would endanger the participant’s health or is likely to result in non-conformance to the protocol. 2. History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder or presence of a significant medical condition that in the opinion of the Investigator precludes participation in the study. Known or suspected impairment of immunological function based on medical history and physical examination. 3. Clinical evidence of active gastrointestinal illness and acute disease at the time of enrolment. 4. Participation in research involving another investigational product 30 days before planned date of first vaccination. 5. Receiving any other vaccines given within 7 days before ETVAX® vaccination. 6. Antibiotics administered within 7 days before ETVAX® vaccination. 7. Febrile illness within 48 hours prior to vaccination or documented fever at the time of immunization (fever is defined as a temp ≥ 37.5°C) 8. Prior receipt of Dukoral, an oral cholera vaccine, or any ETEC vaccine. 9. Prior receipt of a blood transfusion or blood products, including immunoglobulins. 10. Current use of iron or zinc supplements within the past 7 days. 11. Current use of antacids (H2 blockers, omeprazole, over the counter agents or immunosuppressive drug within the past 7 days. 12. Any condition that in the opinion of the PI might jeopardize the safety of study participants or interfere with the evaluation of the study objectives. 13. Diarrhoea during 7 days before vaccination. 14. Acute disease at the time of enrolment or during the 3 days prior to enrolment. 15. Participant’s parents not able, available or willing to accept active follow-up by the study staff. 16. History of chronic administration (defined as more than 14 days) of immunosuppressants 17. Malnutrition (wt-for-ht z-score <-2.0) Infant: 13 Month(s)-24 Month(s) 6 Month(s) 18 Month(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 13/11/2019 Gambia Government MRC Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
PO Box 273 Banjul UNK Gambia
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 15/11/2019 LSHTM Ethics
Ethics Committee Address
Street address City Postal code Country
Keppel Street London WC1E 7HT United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety • Occurrence of serious adverse events (SAEs) among all enrolled children from receipt of the first vaccine dose to end of trial and among the reactogenicity cohort (n=350), reactogenicity and adverse events (AEs) identified during 7 days after receiving each dose of vaccine. from receipt of first dose to end of study
Primary Outcome Efficacy • The first episode of clinically significant acute diarrhoea associated with culture-detected ETEC expressing CFA/I, CS3, CS5, CS6 and/or LT-enterotoxin without co-pathogens among children 6 to 18 months of age receiving two doses and a booster dose (three doses) and detected from 7 days after receiving the third dose of vaccine or placebo through, on average, 18 months of follow up. from 7 days after receiving 3rd dose throughout the follow-up period
Secondary Outcome • The first episode of clinically significant (moderate-to-severe) acute diarrhoea associated with culture-detected ETEC expressing CFA/I, CS3, CS5, CS6 and/or LT-enterotoxin without copathogens among children 6 to 18 months of age receiving two doses of ETVAX with dmLT or placebo detected from 7 days after receiving the second dose of vaccine or placebo through day 90 • The first episode of clinically significant acute diarrhoea associated with culture-detected ETEC regardless of CF or enterotoxin without copathogens among children 6 to 18 months of age receiving three doses of vaccine or placebo detected from 7 days after receiving the third dose through, on average, 18 months of follow up. • The first episode of clinically significant acute diarrhoea episodes regardless of etiology among children 6 to 18 months of age receiving three doses of vaccine or placebo detected from 7 days after receiving the third dose through, on average, 18 months of follow up. • The first episode of moderate to severe diarrhoea with three or more loose or liquid stools associated with ETEC expressing CFA/I, CS3, CS5, CS6 or LTenterotoxin from 7 days after the second dose to third dose and from 7 days after the third dose to study end. from 7 days after receiving the third dose through, on average, 18 months of follow up
Secondary Outcome Immunology: • In a subset of participants (n=150), the proportion of individuals mounting a serum IgA antibody response detected by ELISA to at least one, two, three, four and five of the five primary vaccine antigens (≥ two-fold increase in antibody titres between baseline and after the second and/or third vaccine dose). • The proportion of participants in the subset, mounting a serum IgG antibody response detected by ELISA against LTB (≥ two-fold increase in antibody titres between baseline and after the second and/or third vaccine dose. after the second and/or third vaccine dose
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Medical Research Council Unit The Gambia at the LSHTM Atlantic Boulevard, Fajara Banjul 273 Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP European and Development Countries Clinical Trials Partnership Anna van Saksenlaan 51 The Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Scandinavian Biopharma Holding AB Industrivagen 1 Solna SE-171 48 Sweden Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
SYNLAB Suomi Oy Kivihaantie 7 Helsinki FI-00310 Finland
University of Gothenburg Medicinaregatan 7A Gothenburg 41390 Sweden
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Jahangir Hossain jhossain@mrc.gm +2207504458 Atlantic Boulevard, Fajara
City Postal code Country Position/Affiliation
Banjul UNK Gambia Clinical epidemiologist MRC The Gambia at LSHTM
Role Name Email Phone Street address
Scientific Enquiries Nils Carlin nils.carlin@etvax.se +46701851062 Industrivagen 1
City Postal code Country Position/Affiliation
Solna 17148 Sweden Chief Scientific Officer at Scandinavian Biopharma
Role Name Email Phone Street address
Public Enquiries Andrea Westerdahl andrea.westerdahl@scandinavianbiopharma.se +46761420225 Industrivagen 1
City Postal code Country Position/Affiliation
Solna 17148 Sweden Clinical Operations Mgr at Scandinavian Biopharma
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary results for primary and secondary objectives will be published. The underlying data (de-identified) will be stored at Sponsor´s site after the completion of the study. Clinical Study Report The summary results of the study will be disclosed within 12 months from study completion. Results will be published in scientific publications either in ‘gold’ open access journals or conferences, or in journals or conferences that allow ‘green’ open access publishing within a maximum limit of six months after initial appearance of the publication. The de-identified data collected during study may be made available only by concrete permission of the Sponsor. Any data shared will respect subject confidentiality and will adhere to all regulatory requirements and ethical standards. Shared data will contain appropriate metadata to allow maximum use for secondary studies with the aim to enhance the long-term value of generated data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 31/10/2024
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information