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.: PACTR202408653853505 Date of Approval: 02/08/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A study to expand safety and immunogenicity data with the second generation of the Shigella bioconjugate tetravalent (Shigella4V2) in 9-month-old Kenyan infants.
Official scientific title Safety and immunogenicity of a second generation Shigella bioconjugate vaccine: a phase II randomized, controlled, and blinded study in 9-month-old infants
Brief summary describing the background and objectives of the trial Diarrheal diseases (DDs) are common in LMICs with poor access to clean water, sanitation, and urgent medical care. Shigellosis in particular accounts for 13.2% of all DD deaths globally and is responsible for approximately 212,000 annual deaths. Mortality rates are high, with diarrhea killing almost half a million children under 5 years old each year worldwide. Diarrhea is the fourth leading cause of death for children and is responsible for 8.6% of all deaths of children aged under 5. The most frequent strains causing diarrhea are S. sonnei and S. flexneri serotypes 2a, 6, 3a, 2b and 1b. In this study, the optimized tetravalent bioconjugate candidate vaccine Shigella4V2 will be tested to confirm the data on its safety and immunogenicity in infants obtained using the first generation Shigella4V (S4V01 trial). Objective of this study is also to identify the preferred dose of Shigella4V in 9 month old infants. Shigella4V2 is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Shigella serotypes. Infants will be randomized to receive 1 of 2 different vaccine doses or a control vaccine. A 2 dose schedule will be used. Each study vaccine dose will be formulated with Aluminium adjuvant PRIMARY ENDPOINTS 1. Safety: Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of solicited and unsolicited adverse events (AEs) and serious AEs (SAEs), through: solicited local and systemic AEs during 7 days following each vaccination; unsolicited AEs during 28 days following each vaccination; SAEs and medically relevant AEs throughout the study 2. Immunogenicity: Evaluation of geometric mean titers (GMT) and geometric mean ratios between baseline and 1-month post 2nd vaccination (GMR vs baseline) for serum IgG against the four Shigella serotypes included in the Shigella4V2 bioconjugate.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) S4V02
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Shigellosis
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 17/02/2025
Actual trial start date 25/03/2025
Anticipated date of last follow up 27/02/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 110
Actual target sample size (number of participants)
Recruitment status Recruiting
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
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 Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group low dose 2 vaccinations, 3 months apart Biological: Shigella4V2 adjuvanted vaccine - low dose 40
Experimental Group high dose 2 vaccinations, 3 months apart Biological: Shigella4V2 adjuvanted vaccine - high dose 40
Control Group control vaccine 2 vaccinations, 3 months apart Biological: MenACWY vaccine (marketed product) 30 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Female or male aged 9 months (± 1 month) old at the time of the first vaccination. 2. Born full-term (i.e., after a gestation period of 37 to less than 42 full weeks). 3. Healthy by medical history, laboratory findings and physical examination before entering into the study (Participants with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. 4. Seronegative for HIV, hepatitis B and C (as per screening laboratory tests). 5. Resident of Siaya County during the whole trial period. 6. Previously completed routine primary vaccinations (6,10 and 14 weeks or thereabouts) to the best knowledge of the participant’s parent/guardian. This information will be abstracted from the maternal and child health booklet. All the participant’s parent/guardian will be requested to carry this booklet whenever they visit the clinic. 7. Signed/thumb printed informed consent, in accordance with local practice, provided by participants’ parents or guardian who, in the opinion of the investigator, can and will comply with the requirements of the protocol. 8. Demonstrated comprehension (by the parent/guardian) of the protocol procedures through passing a written/verbal comprehension test with a score of 80% or higher (at least 10 out of 12 questions). 1. Any clinically significant deviation from the normal range in biochemistry or hematological blood tests. 2. Suspected or known hypersensitivity (including allergy) to any of the vaccine components or to previous vaccine, or to medicinal products or medical equipment whose use is foreseen in this study 3. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws 4. Any confirmed or suspected immunosuppressive or immune-deficient condition. 5. Systemic administration of corticosteroids (PO/IV/IM): prednisone ≥20 mg/day, or equivalent for more than 14 consecutive days from birth within 90 days prior to informed consent. Inhaled except for doses > 800 mg/day and topical steroids are allowed. 6. Administration of antineoplastic or radiotherapy from birth / within 90 days prior to informed consent. Participants may be on chronic or as needed medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition 7. Known exposure to Shigella during lifetime of the study participant 8. Concurrently participating in another clinical study, or participation in the preceding month, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device). 9. Acute illness with or without fever is a temporary exclusion criterium. Positive malaria test is a temporary exclusion criterion. 10. History of any malignancy of lymphoproliferative disorder 11. Parent/guardian known to be part of study personnel or being a close family member to the personnel conducting this study. 12. Previous history of significant persistent neutropenia, or drug related Neutropenia 13. Weight-for-age Z score less than -3SD. 14. History of any chronic or p Infant: 13 Month(s)-24 Month(s) 8 Month(s) 10 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 04/06/2024 Scientific Ethics Review Unit SERU KEMRI
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way Nairobi 54840 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of solicited AEs During 7 days following each vaccination
Primary Outcome Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of unsolicited AEs During 28 days following each vaccination
Primary Outcome Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of SAEs Throughout the study, up to 9 months
Primary Outcome Evaluation of geometric mean titers (GMT) and geometric mean ratios between baseline and 1- month post 2nd vaccination (GMR vs baseline) for serum IgG against the four Shigella serotypes included in the Shigella4V2 bioconjugate From first vaccination until 1 month following the second vaccination
Secondary Outcome Measuring clinically significant changes in hematological and biochemical safety parameters comparing values before injection (baseline) and 7 days following each vaccine administration From first vaccination until 7 days following each vaccination
Secondary Outcome Evaluation of geometric mean titers (GMT) for serum IgG against the four Shigella serotypes included in Shigella4V2 at 6 months post 2nd vaccination From first vaccination until 6 months post 2nd vaccination
Secondary Outcome Serum IgG responses and fold-increases between baseline and post-vaccination samples against the four Shigella serotypes included in the Shigella4V2 bioconjugate From first vaccination until 6 months post 2nd vaccination
Secondary Outcome Percentage of study participants achieving at least a four-fold increase in anti-Shigella LPS antibody titers (sero-responders) 1-month post 2nd vaccination compared to baseline From first vaccination up to 1 month post 2nd vaccination
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Siaya County Referral Hospital Hospital Road Siaya Township Alego Usonga Siaya Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
LimmaTech Biologics AG Grabenstrasse 3 Schlieren 8952 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor LimmaTech Biologics AG Grabestrasse 3 Schlieren 3 8952 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Richard Omore ronyando@kemri.go.ke +254723813788 1578-40100 Kisumu, Kenya
City Postal code Country Position/Affiliation
Kisumu Kenya KEMRI Center for Global Health Research
Role Name Email Phone Street address
Scientific Enquiries Richard Omore ronyando@kemri.go.ke +254723813788 1578-40100 Kisumu, Kenya
City Postal code Country Position/Affiliation
Kisumu Kenya KEMRI Center for Global Health Research
Role Name Email Phone Street address
Public Enquiries Sidney Ogolla SOOgolla@kemri.go.ke +254723678426 1578-40100 Kisumu,Kenya
City Postal code Country Position/Affiliation
Kisumu Kenya KEMRI Center for Global Health Research
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes IPD (raw, de-identified data) will be shared after publication of primary results Informed Consent Form Not applicable Not applicable
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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 30/07/2024 Addressing comment coming from PACTR review In this study, the optimized tetravalent bioconjugate candidate vaccine Shigella4V2 will be tested to confirm the data on its safety and immunogenicity in infants obtained using the first generation Shigella4V (S4V01 trial). Objective of this study is also to identify the preferred dose of Shigella4V in 9 month old infants. Shigella4V2 is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Shigella serotypes. Infants will be randomized to receive 1 of 2 different vaccine doses or a control vaccine. A 2 dose schedule will be used. Each study vaccine dose will be formulated with Aluminium adjuvant PRIMARY ENDPOINTS 1. Safety: Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of solicited and unsolicited adverse events (AEs) and serious AEs (SAEs), through: solicited local and systemic AEs during 7 days following each vaccination; unsolicited AEs during 28 days following each vaccination; SAEs and medically relevant AEs throughout the study 2. Immunogenicity: Evaluation of geometric mean titers (GMT) and geometric mean ratios between baseline and 1-month post 2nd vaccination (GMR vs baseline) for serum IgG against the four Shigella serotypes included in the Shigella4V2 bioconjugate. Diarrheal diseases (DDs) are common in LMICs with poor access to clean water, sanitation, and urgent medical care. Shigellosis in particular accounts for 13.2% of all DD deaths globally and is responsible for approximately 212,000 annual deaths. Mortality rates are high, with diarrhea killing almost half a million children under 5 years old each year worldwide. Diarrhea is the fourth leading cause of death for children and is responsible for 8.6% of all deaths of children aged under 5. The most frequent strains causing diarrhea are S. sonnei and S. flexneri serotypes 2a, 6, 3a, 2b and 1b. In this study, the optimized tetravalent bioconjugate candidate vaccine Shigella4V2 will be tested to confirm the data on its safety and immunogenicity in infants obtained using the first generation Shigella4V (S4V01 trial). Objective of this study is also to identify the preferred dose of Shigella4V in 9 month old infants. Shigella4V2 is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Shigella serotypes. Infants will be randomized to receive 1 of 2 different vaccine doses or a control vaccine. A 2 dose schedule will be used. Each study vaccine dose will be formulated with Aluminium adjuvant PRIMARY ENDPOINTS 1. Safety: Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of solicited and unsolicited adverse events (AEs) and serious AEs (SAEs), through: solicited local and systemic AEs during 7 days following each vaccination; unsolicited AEs during 28 days following each vaccination; SAEs and medically relevant AEs throughout the study 2. Immunogenicity: Evaluation of geometric mean titers (GMT) and geometric mean ratios between baseline and 1-month post 2nd vaccination (GMR vs baseline) for serum IgG against the four Shigella serotypes included in the Shigella4V2 bioconjugate.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 16/01/2025 Delays with PPB approval process caused postponing of the trial start 18 Nov 2024 17 Feb 2025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 16/04/2025 Trial started its recruitment phase 25 Mar 2025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 16/01/2025 Delays with PPB approval process caused postponing of the trial end 04 Nov 2025 31 Dec 2025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 16/04/2025 Delays in the trial approval process 31 Dec 2025 27 Feb 2026
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 16/04/2025 The trial started its recruitment phase Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 16/01/2025 Change was not saved by the system during the previous update The data produced will be will be pseudonymised and shared with participants' parents/guardians and site staff via a link to the LMTB cloud storage Not applicable
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 30/07/2024 Following PACTR review Final summary of results The data produced will be will be pseudonymised and shared with participants' parents/guardians and site staff via a link to the LMTB cloud storage.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 31/07/2024 Changed in response to comment and to match statement in clinicaltrials.gov The data produced will be will be pseudonymised and shared with participants' parents/guardians and site staff via a link to the LMTB cloud storage. Not available
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 02/08/2024 PACTR Admin Not available The data produced will be will be pseudonymised and shared with participants' parents/guardians and site staff via a link to the LMTB cloud storage
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 13/05/2025 Necessity of IPD statement Not applicable IPD (raw, de-identified data) will be shared after publication of primary results
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 31/07/2024 Changed in response to comment and to match statement in clinicaltrials.gov 2 years Not applicable
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 30/07/2024 Following feedback from PACTR Controlled access to data to participants' parents/guardians and to site staff. Access to data to be requested via email to sponsor (clinical@lmtbio.com) Controlled access to data to participants' parents/guardians and to site staff. Access to data to be requested via email to sponsor (clinical@lmtbio.com). Data will be shared with participants' parents/guardians and to site staff via a link to the LMTB cloud storage service.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 30/07/2024 Following PACTR review Controlled access to data to participants' parents/guardians and to site staff. Access to data to be requested via email to sponsor (clinical@lmtbio.com). Data will be shared with participants' parents/guardians and to site staff via a link to the LMTB cloud storage service. Controlled access to data to participants' parents/guardians and to site staff. Access to data to be requested via email to sponsor (clinical@lmtbio.com).
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 31/07/2024 Changed in response to comment and to match statement in clinicaltrials.gov Controlled access to data to participants' parents/guardians and to site staff. Access to data to be requested via email to sponsor (clinical@lmtbio.com). Not applicable