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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202309532820945 Date of Registration: 14/09/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Trivalent Salmonella Conjugate Vaccine (TSCV)
Official scientific title Age-descending, Randomized, Placebo-controlled Phase 2 Trial in Three Sites in Sub-Saharan Africa to Assess the Safety and Immunogenicity of a Parenteral Trivalent Salmonella (S. Enteritidis/S. Typhimurium/S. Typhi Vi) Conjugate Vaccine (TSCV) Versus Placebo
Brief summary describing the background and objectives of the trial Prior to the 1990s, only limited and spotty information was available on the burden and etiology of invasive bacterial infections among children in different regions and countries across sub-Saharan Africa. This was largely consequent to the scarcity of health care facilities that were equipped to perform cultures of blood, cerebrospinal fluid, and other normally sterile body fluids. With the introductions of conjugate vaccines against Haemophilus influenzae type b (Hib) in the USA and Europe in the 1990s, and against Streptococcus pneumoniae circa 2000, international agencies, including the Global Alliance for Vaccines and Immunization (GAVI) undertook to quantify the burden of invasive Hib and pneumococcal disease in pediatric populations in sub-Saharan Africa. The isolation of S. pneumoniae from blood cultures and serotyping of the isolates was critical not only to estimate the magnitude of the burden of Hib and pneumococcal disease but also to assess whether the 7-valent serotype composition of the pneumococcal conjugate vaccine formulations used in high-income countries would also be relevant for sub-Saharan Africa. • To evaluate the safety and reactogenicity of two, Full-strength and Half-strength, GMP formulations of Trivalent Salmonella (S. Enteritidis/S. Typhimurium/S. Typhi Vi) Conjugate Vaccine (TSCV) administered as a single dose to adults, children, toddlers, and infants in sub-Saharan Africa (sSA), and as two spaced doses (a priming dose at age ~ 12-18 weeks of age and a booster at either 9, 12, or 15-17 months of age), in comparison to Typbar-TCV™ and to placebo. • To select one of the two formulations of TSCV for further clinical development based on non-inferiority comparisons • To evaluate the safety, reactogenicity, and immunogenicity of the selected TSCV formulation given as a priming dose toyoung infants (age 12-18 weeks) who subsequently receive a booster dose of TSCV at age 9,12, or 15 months.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TSCV
Disease(s) or condition(s) being studied non-Typhoidal Salomonella,Paediatrics
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 04/09/2023
Actual trial start date 04/09/2023
Anticipated date of last follow up 05/04/2025
Actual Last follow-up date 30/12/2026
Anticipated target sample size (number of participants) 1368
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://clinicaltrials.gov/ct2/show/NCT05784701?term=trivalent+salmonella+conjugate+vaccine&draw=2&rank=1
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
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Interventional 25mcg 9, 12, 15months 15 months Full strength 456
Experimental Group Interventional 12.5mcg 15months Half strength 456
Control Group Placebo 15 months Placebo 456 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion Criteria: Healthy individuals, female or male Age (all age ranges are inclusive) Step 1A: Adults 20-35 years of age Step 1B: Children, 5-9 years of age Step 1 C: Pre-school children, 24-59 mos. of age Step 1D: Older toddlers, 16-23 months of age Step 2A: Young toddlers, 12-16 months of age Step 2B: Older infants, 8-11 months of age Step 3: Young infants,12-14 weeks of age OR 16-18 weeks of age Step 4: Young infants, 12-18 weeks of age For potential pediatric participants, the parents must live within the catchment area of the clinical study facility at the time of the study vaccinations and must intend to continue to reside in the area for the duration of the study Adult subjects and parents/ guardians of pediatric subjects must have provided informed consent Infant and toddler subjects in Steps 2, 3, and 4 must have received their scheduled EPI vaccines at least 14 days prior to receiving a study product. Exclusion Criteria: A history of documented hypersensitivity to any component of the Trivalent Salmonella Conjugate Vaccine or of Typbar-TCV™ A history of previous vaccination with any licensed or experimental typhoid vaccine A known history of diabetes, tuberculosis, malignancy, chronic kidney disease, cardiac disease, liver disease, progressive neurological disorder, poorly controlled seizure disorder, or a terminal illness based on participant interview and review of screening laboratory results. Severe malnutrition: i.e., weight-for-length Z-score of less than - 3. Receipt of any other investigational intervention in the last 6 months Known HIV infection or other forms of immunocompromise Receipt of systemic immunosuppressive medication including systemic corticosteroids For Step 1A, for females of child-bearing potential, a positive pregnancy test at the time of enrollment. For Step 1B, any female child who has experienced menarche Adult: 18 Year(s)-44 Year(s),Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 12 Week(s) 35 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 27/04/2023 Scientific and Ethical Review Commitee
Ethics Committee Address
Street address City Postal code Country
KENYA MEDICAL RESEARCH INSTITUTE SCIENTIFIC AND ETHICS REVIEW UNIT P.O. BOX 54840 00200 OFF MBAGATHI ROAD, NAIROBI, KENYA NAIROBI 00200 Kenya
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 30/12/2022 USTTB Ethics Commitee
Ethics Committee Address
Street address City Postal code Country
Faculte De Pharmacie/BP 1805, Bamako Mali Bamako 1805 Mali
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety and reactogenicity of Full-strength and Half-strength TSCV [ Time Frame: first 30 minutes after parenteral immunization ] The proportion of participants in each product group and within each age group who develop adverse events (AEs) in the first 30 minutes after parenteral immunization Safety and reactogenicity of Full-strength and Half-strength TSCV [ Time Frame: over 7 days post-vaccination. ] The proportion of participants in each product group and within each age group who develop adverse events (AEs) in the 7 days post-vaccination. Safety and reactogenicity of Full-strength and Half-strength TSCV [ Time Frame: through Day 29 of follow-up post-vaccination ] The proportion of participants who experience AEs through Day 29 of follow-up post-vaccination. Safety and reactogenicity of Full-strength and Half-strength TSCV [ Time Frame: Through Day 366 of follow-up post vaccination ] The proportion of participants who experience Serious Adverse Events through their participation in the study. Non-inferiority analysis: immunogenicity of Full-strength vs. Half-strength TSCV [ Time Frame: Through day 29 post vaccination ] Serum IgG anti-COPS antibodies (to both S. Enteritidis and S. Typhimurium antigens) Non-inferiority analysis: immunogenicity of Full-strength vs. Half-strength TSCV [ Time Frame: Through day 29 post vaccination ] Serum IgG anti-Vi antibodies Safety and reactogenicity after primary dose of TSCV and after booster dose of TSCV or Typbar-TCV™ [At each booster age group (9, 12, or 15-17 mo. of age)] [ Time Frame: over 7 days post-vaccination. ] The proportion of participants in each product group who develop adverse events (AEs) in 7 days post-vaccination. Safety and reactogenicity after primary dose of TSCV and after booster dose of TSCV or Typbar-TCV™ [At each booster age group (9, 12, or 15-17 mo. of age)] [ Time Frame: through Day 29 of follow-up after each vaccination. ] The proport All time points
Secondary Outcome B memory responses. Systems Serology Opsonophagocytic activity (OPA) All time points
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KENYA KISUMU KISUMU 40100 Kenya
MALI MALI BAMAKO Mali
FUNDING SOURCES
Name of source Street address City Postal code Country
The Wellcome Trust Wellcome Trust Gibbs Building 215 Euston Road London NW1 2BE London United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Maryland 620 W Lexington St, Baltimore, MD 21201, United States Baltimore 21201 United States of America University
COLLABORATORS
Name Street address City Postal code Country
Bharat Biotech International 230 231235 Genome Valley Hyderabad 500078 India
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Miligritos Tapia MTAPIA@som.umaryland.edu +14107065328 655 W. Baltimore Street
City Postal code Country Position/Affiliation
Baltimore MD 21201 United States of America Proffesor
Role Name Email Phone Street address
Public Enquiries Alyson Kwon akwon@som.umaryland.edu +14107060850 655 W. Baltimore Street
City Postal code Country Position/Affiliation
Baltimore MD 21201 United States of America Regulatory Affairs Specialist
Role Name Email Phone Street address
Scientific Enquiries Fleesie Hubbard fhubbard@som.umaryland.edu +14107060850 655 W. Baltimore Street
City Postal code Country Position/Affiliation
Baltimore MD 21201 United States of America International Regulatory Affairs Specialist
Role Name Email Phone Street address
Principal Investigator Richard Omore omorerichard@gmail.com +254723678426 KEMRI CGHR, OFF BUSIA
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Senior Research Scientist
Role Name Email Phone Street address
Principal Investigator Samba Sow ssow@cvd-mali.org +22320236031 Center for Vaccine Development Mali, Ex Institut Marchoux, Avenue Mohamed VI, Djikoroni Para, 251 Bamako, Mali
City Postal code Country Position/Affiliation
Bamako Mali Proffessor CVD Mali
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes De-identified data will be summarized and shared in aggregate. There is no plan to share individual level data as it is not required by the funder. Study Protocol De-identified data will be summarized and shared in aggregate two years after the end of the trial NO
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