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.: PACTR202310834458532 Date of Approval: 05/10/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Salmonella Vaccine Immunogenicity and Safety (SaVIS) Study
Official scientific title A Phase 1 Clinical Study to Evaluate the Safety and Immunogenicity of a Novel GMMA Vaccine Against Invasive Non-Typhoidal Salmonella in healthy Kenyan adults.
Brief summary describing the background and objectives of the trial Invasive non-typhoidal Salmonella disease causes a high burden of morbidity and mortality in sub-Saharan Africa. A bivalent vaccine against both S. Typhimurium and S. Enteritidis has been developed by the GSK Vaccines Institute for Global Health, using a new technology that utilizes outer membrane vesicles derived from genetically-modified bacteria (the Generalized Modules for Membrane Antigens technology). This iNTS-GMMA vaccine has been shown to be immunogenic and non-toxic in animal studies. The objective of this trial is to assess the safety and immunogenicity of this iNTS-GMMA vaccine among healthy adults in Kenya.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SAVIS
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied non-typhoidal Salmonella
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 16/01/2024
Actual trial start date
Anticipated date of last follow up 16/05/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 120
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
H04 02TP GSK Vaccines Institute for Global Health
SERU4744 KEMRI Scientific and Ethics Review Unit
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 Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Low Dose 2.66µg of iNTS-GMMA 3 doses given at 0, 2 and 6 months This group will receive 2.66µg of the iNTS-GMMA vaccine comprising of 1.33 µg (O-Antigen) S Typhimurium and 1.33µg (O-Antigen) S Enteritidis. The vaccine will be administered as 3 doses given at 0, 2 and 6 months. 30
Experimental Group Medium Dose 10.6 µg of iNTS-GMMA 3 doses given at 0, 2 and 6 months This group will receive the medium dose of iNTS-GMMA vaccine comprising of 5.3ug of O-Antigen S Typhimurium and 5.3ug of O-Antigen S Enteritidis. The vaccine will be administered as 3 doses given at 0, 2 and 6 months. 30
Experimental Group Full Dose 40µg of iNTS-GMMA 3 doses at 0, 2 months and 6 months This group will receive 40µg of the iNTS-GMMA vaccine comprising of 20 µg (O-Antigen) S Typhimurium and 20µg (O-Antigen) S Enteritidis. The vaccine will be administered as 3 doses given at 0, 2 and 6 months. 30
Control Group iNTS Placebo MenVeo vaccine given on day 0; Alhydrogel placebo given at 2-months and 6-months 3 doses given at 0, 2 months and 6 months. The iNTS-Placebo given as the first dose will be the MenACWY (Menveo)Vaccine while on the second and third doses the placebo will be a suspension of aluminium hydroxide (0.7 mg Al3+ / ml) in buffered saline (Alhydrogel) 30 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Written or witnessed/thumb printed informed consent obtained from the participant. Aged between 18 – 45 years In good health as determined by study clinician by: Medical history, Physical examination and heamatology and biochemistry laboratory assessments and Clinical judgement of the investigators Participants satisfying all screening requirements. Participants seronegative for HIV, hepatitis B, and hepatitis C. Females willing to use effective contraception and should be on contraception for at least one month prior to receiving the first vaccine and for the duration of the study. Able to attend the scheduled visits and to comply with all study procedures History of significant organ/system disease that could interfere with the trial conduct or completion in the clinical judgement of the investigators. Have any known or suspected impairment or alteration of immune function Study significant abnormalities on screening that are either unlikely to resolve or do not resolve on repeat testing Known exposure to non typhoidal Salmonella during lifetime of the subject participant as documented by patient records (e.g., history of microbiologically-confirmed NTS infection) History of any reaction or hypersensitivity likely to be exacerbated by any component of the study. Receipt of a live vaccine within 4 weeks prior to vaccination or a killed vaccine within 7 days prior to vaccination Prior receipt of a typhoid vaccine or the Shigella GMMA vaccine. Plan to receive any vaccine other than the study vaccine within 4 weeks after vaccination. COVID19 vaccines are an exception. Scheduled procedures requiring general anaesthesia during the study Participant who is terminally ill Receipt of immunoglobulin or any blood product transfusion within 3 months of study start Participation in another clinical research study involving an investigational product or a non-investigational intervention (drug or invasive medical device) in the past 12 weeks, or are planning to do so at any point within the trial period Inability, in the opinion of the Investigator, to comply with all study requirements including likelihood of successful venepuncture during the trial Female participants who are pregnant, breastfeeding/lactating or planning pregnancy during the course of the study Weight less than 45kg or a BMI < 18.4 kg/m2 or a BMI > 40 kg/m2 Any other significant disease or disorder which, in the opinion of the Investigator, may: • Put the participants at risk because of participation in the study • Influence the result of the study • Impair the participant’s ability to participate in the study Adult: 19 Year-44 Year 18 Year(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 01/09/2023 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O BOX 54840 Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The safety and reactogenicity of the iNTS-GMMA vaccine. The following solicited adverse events will be assessed: 1. Tenderness and pain at the injection site 2. Induration at the injection site 3. Redness at the injection site 4. Swelling at the injection site 5. Headache 6. Malaise 7. Myalgia 8. Nausea and/or vomiting 9. Diarrhoea 10. Abdominal Pain 11. Anorexia 12. Fever 13. Arthralgia 14. Fatigue Blood parameters (haematology/biochemistry) Any unsolicited symptom(s) not listed above in addition to any other AE, SAE or SUSAR Daily home visits after each vaccine dose for 6 days, and clinical assessments on day 7 and day 28 following administration of each vaccine dose.
Secondary Outcome Antibody concentration against S. Typhimurium O antigen and S. Enteritidis O-antigen determined by enzyme linked immunosorbent assay (ELISA) before and 28 days after each dose. Exploratory outcomes include Immunological assays to study the immune responses to vaccines, including but not limited to: 1. Antibody concentration against other potential antigens including porins determined by enzyme linked immunosorbent assay (ELISA) before and after each dose 2. Serum bactericidal antibody (SBA) titre against a panel of vaccine homologous strains before and after each dose 3. Functional antibody analyses which may include opsonophagocytic assays and glycosylation 4. Measurement of antibody persistence 6 months after 3rd dose of vaccine. 5. Quantification of circulating vaccine-induced B-cells responses specific for vaccine antigens before and after each dose 6. Quantification of vaccine-induced, antigen specific T-cell responses and associated cytokine production before and after each dose 7. Gene expression profile after immunization and DNA storage for investigation of the genetic associations with the immune response 8. Faecal antibody concentration against O antigen determined by enzyme linked immunosorbent assay (ELISA) before and after each dose of the vaccine 9 Stool carriage of non-typhoidal Salmonella before and after each dose. before and 28 days after each vaccine dose
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI Wellcome Trust Research Programme P.O BOX 230 Kilifi 80108 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
EU Horizon2020 grant to VacciNTS consortium Pizza la Lizza 7 Siena 53100 Italy
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford Wellington Square Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
GSK Vaccines Institutes for Global Health Via Fiorentina 1 Siena 53100 Italy
University of Oxford Wellington Square Oxford OX1 2JD United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Anthony Scott ascott@kemri-wellcome.org +254110920262 Hospital Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Senior Research Scientist
Role Name Email Phone Street address
Scientific Enquiries Esther Muthumbi emuthumbi@kemri-wellcome.org +254110920262 Hospital Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Trial Coordinator
Role Name Email Phone Street address
Public Enquiries Community Liason Manager nmumba@kemri-wellcome.org +254417522063 Hospital Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Head Community Liaison group
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Anonymized information collected or generated during this study may be used to support new research. A clean de-identified database may be provided as publicly available (‘open access’) or upon reasonable request, after the final study publication is published, as per the relevant medical journal regulations. Study Protocol After study has been published Any future research using information from this study, must first be approved by a local or national ethics committee to make sure that the interests of participants and their communities are protected. Data requests can be made to the data governance team at the KEMRI-Wellcome Trust Research Programme
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 URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information