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.: PACTR201905764389804 Date of Approval: 14/05/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title ETVAX
Official scientific title A Phase 1 age descending placebo controlled clinical trial to examine the safety, tolerability, and immunogenicity of an oral inactivated ETEC Vaccine (ETVAX®) in healthy adults and children in Zambia.
Brief summary describing the background and objectives of the trial Diarrhoea remains one of the major causes of morbidity and death among children below five years of age living in developing counties. The majority of cases of diarrhoea which end in death occur in children below the age of two. Enterotoxigenic Escherichia coli (ETEC) is one of the top four pathogens that causes moderate to severe diarrhoea (MSD) and while strides have been made to develop vaccines for these pathogens there is currently no licensed vaccine for ETEC. ETEC is also associated with other long-term negative health and economic impacts for children and their families in low- resource countries. Establishing the protective efficacy of promising ETEC vaccine candidates is a high priority for the World Health Organization and European & Developing Countries Clinical Trial Partnership (EDCTP). This study seeks to evaluate a vaccine against ETEC diarrhoea called ETVAX®. The objectives are to establish the safety and immunogenicity of ETVAX® in children aged 6-9 month old and 10-23 month old, respectively in Zambia. Our team aims to move ETVAX®, an inactivated whole cell vaccine candidate, into advanced clinical development including field efficacy testing. This is a Phase 1 age descending study in adults, children 10-23 months and children 6-9 months to establish the safety and immunogenicity of ETVAX® in Zambia.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) OEV124
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 21/06/2019
Actual trial start date 21/09/2019
Anticipated date of last follow up 30/09/2020
Actual Last follow-up date 10/09/2020
Anticipated target sample size (number of participants) 246
Actual target sample size (number of participants) 246
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table from a statistics book Allocation was determined by the holder of the sequence who is situated off site 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 Cohort A adults 18 to 45 years 153ml (150ml buffer + 3.3ml ETVAX vaccine + 0.05ml dmLT) once during the duration of the study 35 days The first cohort (Cohort A) will enrol a total of 40 adult participants (30 vaccinees and 10 placebos). Participants will be randomized to receive one administration of full dose of ETVAX® + 10 μg dmLT or placebo in a double blinded manner. ETVAX® will be administered at full dose (10^11 inactivated E. coli bacteria). The placebo preparation will be sodium bicarbonate buffer. Cohort A will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 15%. 30
Control Group Cohort A adults 18 to 45 years inclusive 153ml placebo (150ml buffer +3.3ml water) once for the duration of the study 35 days The first cohort (Cohort A) will enrol a total of 40 adult participants (30 vaccinees and 10 placebos). Participants will be randomized to receive one administration of full dose of ETVAX® + 10 μg dmLT or placebo in a double blinded manner. ETVAX® will be administered at full dose (10^11 inactivated E. coli bacteria). The placebo preparation will be sodium bicarbonate buffer. Cohort A will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 15%. the DSMB will review available safety data through 7 days after the first immunization to make a recommendation to the sponsor whether to proceed with the initiation of Cohort B (10-23 month old infant) 10 Placebo
Experimental Group Cohort B1 children 10 to 23 months inclusive 3 doses of: 10.4ml (0.413ml ETVAX + 0.0125ml dmLT + 10ml buffer) first dose on day 1; second dose on day 15 and third dose on day 90 120 The second cohort (Cohort B) will enrol a total of 60 children aged 10-23 month old, inclusive (40 vaccines and 20 placebos) . The cohort will include 20 children, randomized to receive three administrations of ETVAX® at 1/8 dose with 2.5 μg dmLT (20 children) or 1/4 dose with 2.5 μg dmLT (20 children) or placebo (20 children). The DSMB will review available safety data through 7 days after the second immunization to make a recommendation to the Sponsor whether to proceed with the initiation of Cohort C (cohort in 6-9 month-old children). Cohort B will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 15%. 20
Control Group Cohort B1 Children 10 to 23 months inclusive 3 doses of: 10.4ml (0.43ml water + 10ml buffer) first dose on day 1; second dose on day 15 and third dose on day 90 120 days The second cohort (Cohort B) will enrol a total of 60 children aged 10-23 month old, inclusive (40 vaccines and 20 placebos) . The cohort will include 20 children, randomized to receive three administrations of ETVAX® at 1/8 dose with 2.5 μg dmLT (20 children) or 1/4 dose with 2.5 μg dmLT (20 children) or placebo (20 children). The DSMB will review available safety data through 7 days after the second immunization to make a recommendation to the Sponsor whether to proceed with the initiation of Cohort C (cohort in 6-9 month-old children). Cohort B will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 15%. 10 Placebo
Experimental Group Cohort B2 Children 10 to 23 months inclusive 10.84ml (0.825ml ETVAX + 0.0125ml dmLT + 10 ml buffer) first dose on day 1, second dose on day 15 and third dose on day 90 120 days The second cohort (Cohort B) will enrol a total of 60 children aged 10-23 month old, inclusive (40 vaccines and 20 placebos) . The cohort will include 20 children, randomized to receive three administrations of ETVAX® at 1/8 dose with 2.5 μg dmLT (20 children) or 1/4 dose with 2.5 μg dmLT (20 children) or placebo (20 children). The DSMB will review available safety data through 7 days after the second immunization to make a recommendation to the Sponsor whether to proceed with the initiation of Cohort C (cohort in 6-9 month-old children). Cohort B will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 15%. 20
Control Group Cohort B2 Children 10 to 23 months inclusive 10.8 ml placebo (10ml buffer + 0.84 ml water) first dose on day 1, second dose on day 15 and third dose on day 90 120 days The second cohort (Cohort B) will enrol a total of 60 children aged 10-23 month old, inclusive (40 vaccines and 20 placebos) . The cohort will include 20 children, randomized to receive three administrations of ETVAX® at 1/8 dose with 2.5 μg dmLT (20 children) or 1/4 dose with 2.5 μg dmLT (20 children) or placebo (20 children). The DSMB will review available safety data through 7 days after the second immunization to make a recommendation to the Sponsor whether to proceed with the initiation of Cohort C (cohort in 6-9 month-old children). Cohort B will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 15%. 10 Placebo
Experimental Group Cohort C1 infants 6 to 9 months inclusive 10ml (0.413ml ETVAX + 0.0125ml dmLT + 10ml buffer) first dose on day 1, second dose on day 15 and third dose on day 90 120 days The third cohort (Cohort C) will enrol a total of 146 children randomized to receive three administrations of ETVAX® at 1/4 (55 children) dose or 1/8 dose (55 children) with 2,5 μg of dmLT or placebo (36 children). Cohort C will have approximately 90% chance of observing at least one adverse event of special interest for events that occur at a rate of 7.4% 55
Control Group Cohort C1 infants 6 to 9 months inclusive 10.4ml (10ml buffer + 0.43ml Water) first dose on day 1, second dose on day 15 and third dose on day 90 120 days The third cohort (Cohort C) will enrol a total of 146 children, randomized to receive three administrations of ETVAX® at 1/4 (55 children) dose or 1/8 dose (55 children) with 2,5 μg of dmLT or placebo (36 children). Part C will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 7.4%. C will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 7.4% 18 Placebo
Experimental Group Cohort C2 infants 6 to 9 months inclusive 10.84ml (0.825ml ETVAX + 0.0125ml dmLT + 10ml buffer) first dose on day 1, second dose on day 15 and third dose on day 90 120 days The third cohort (Cohort C) will enrol a total of 146 children, randomized to receive three administrations of ETVAX® at 1/4 (55 children) dose or 1/8 dose (55 children) with 2,5 μg of dmLT or placebo (36 children). Cohort C will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 7.4% 55
Control Group Cohort C2 infants 6 to 9 months inclusive 10.8 ml placebo (0.84ml water + 10ml buffer) First dose on day 1, second dose on day 15, third dose on day 90 120 days The third cohort (Cohort C) will enrol a total of 146 children, randomized to receive three administrations of ETVAX® at 1/4 (55 children) dose or 1/8 dose (55 children) with 2,5 μg of dmLT or placebo (36 children). Cohort C will have an approximately 90% chance of observing at least one serious adverse event or adverse event of special interest for events that occur at a rate of 7.4% 18 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Healthy male or non-pregnant female adults ages 18 to 45 years old and children ≥6 and ≤23 months old at the time of enrolment, all inclusive. • General good health as determined by the screening evaluation conducted 1-7 days before enrolment and vaccination. • Adult subjects or parents to children properly informed about the study, able to understand it and sign or thumbprint the informed consent form. • Subject, parent and child available for the entire study period of the study and reachable by study staff throughout the entire follow-up period. • Willing to comply with all stipulated study procedures. 1. Presence of any significant known systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) 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 or designee precludes participation in the study. 3. Known or suspected impairment of immunological function based on medical history and physical examination. 4. Clinical evidence of active gastrointestinal illness and acute disease at the time of enrolment 5. Participation in a research study involving another investigational product (defined as receipt of investigational product) including 30 days before planned date of first vaccination. 6. History of receiving any other vaccine within 7 days before ETVAX® vaccination. 7. Antibiotic administered within 7days before ETVAX® vaccination. 8. History of febrile illness within 48 hours prior to vaccination and fever at the time of immunization (fever is defined as a temperature ≥ 37.5 C ) on axillary measurement 9. Prior receipt of oral cholera vaccine (specifically Dukoral®) or any ETEC vaccine. 10. Prior receipt of a blood transfusion or blood products, including immunoglobulins. 11. Current use of iron or zinc supplements within the past 7 days; 12. Current use of antacids (H2 blockers, omeprazole, OTC agents) within the past 7 days 13. current use of immunosuppressive drug (e.g steroids) within the past 7 days. 14. Receipt of antimicrobial drugs for any reason within 7 days before vaccination 15. History of diarrhoea during the 7 days before vaccination 16. Acute disease at the time of enrolment or during the 3 days prior to enrolment 17. Participant’s or parents/guardians not being able to or unwilling to accept active follow-up by the study staff 18. History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study 19. Medically significant malnutrition, defined as moderate or more severe malnutrition (BMI <18.5 kg/m2 for Cohort A, weight-for-height z-score < - 2.0 SD for Cohort B and C) 20. Any condition which in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Infant: 1 Month-23 Month,Middle Aged: 45 Year(s)-64 Year(s) 6 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 27/02/2019 University of Zambia Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus Nationalist Road Lusaka 10101 Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety will be assessed by analyses of the following primary endpoints (events), where the unit of analysis in each case will be the proportion of participants with at least one event: • Solicited gastrointestinal reactions • Solicited systemic reactions • Unsolicited adverse events • Adverse events where there is a reasonable possibility that the study product caused the event, i.e., are suspected adverse drug reactions • Serious adverse events 120 days
Secondary Outcome Immunogenicity Analysis for all immunological analyses, the response rate and magnitude of antigen-specific responses will be analyzed after second and third immunization as specimen availability allows. Response rates to the five primary antigens in the ETVAX® vaccine (LTB, CFA/I, CS3, CS5, and CS6) will be further evaluated to address co-secondary immunogenicity hypothesis by analyzing the response rates to at least three of the five different antigens by faecal SIgA and plasma IgA. The specific objective about to assess memory B-cell responses to LTB, CFA/I, CS3, CS5 and CS6 on adults was relabeled to an exploratory objective. The analysis of this exploratory objective will be addressed later on and results reported through an academic PhD research project at CIDRZ. analyzed after second day 15, and third immunization day 90 as specimen availability allows.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Matero Clinical Research Site Matero Ref Level 1 Hospital 3160 Chitimukulu Road Lusaka 10101 Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership EDCTP 51 Anna Van Saksenlaan the Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Scandinavian Biopharma Industrivagen 1, Solna 17148 Sweden Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
University of Gothenberg 7A Medcinaregatan Goteborg 41390 Sweden
Centre for Infectious Disease Research in Zambia CIDRZ Plot 34620 off Alick Nkhata road Mass Media Lusaka 10101 Zambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Roma Chilengi roma.chilengi@cidrz.org +260973724935 plot 34620 off Alick Nkhata Road, Mass media
City Postal code Country Position/Affiliation
Lusaka 10101 Zambia Chief Scientific Officer CIDRZ
Role Name Email Phone Street address
Public Enquiries Hope Mwanyungwi hope.mwanyungwi@cidrz.org +260966933970 plot 34620 off Alick Nkhata Road, Mass Media
City Postal code Country Position/Affiliation
Lusaka 10101 Zambia Head of Research Operations CIDRZ
Role Name Email Phone Street address
Scientific Enquiries Nils Carlin nils.carlin@etvax.se +46701851062 1 Industrivagen
City Postal code Country Position/Affiliation
Solna 17148 Sweden Vice President Research and development 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 Within 12 months of the completion of the study. The 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
Yes 03/02/2022
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 03/02/2022
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information