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.: PACTR202402550507294 Date of Approval: 20/02/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A study on the immunogenicity and safety of GSK Vaccines Global Health multicomponent Shigella vaccine in preventing shigellosis in infants
Official scientific title A Phase 2 single-blind, randomized, controlled, single center study to assess the immunogenicity and safety of a 2-dose schedule with GVGH altSonflex1-2-3 vaccine in African infants (H06_02TP)
Brief summary describing the background and objectives of the trial Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in LMIC, particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238 000 deaths globally and it ranked second with regard to pathogen contributions in global diarrheal deaths (15.2%) [IHME, 2017]. In infants, in LMIC, particularly when healthcare resources are limited, shigellosis can often lead to death. In 2016, Shigella was responsible for 63 713 deaths among children less than 5 years of age and 212 438 deaths among all ages [GBD, 2018]. There is presently no widely available vaccine against Shigella. Treatment for shigellosis is mainly supportive to keep patients stable and restore lost electrolytes due to diarrhea. If available, specific antibiotics are sometimes used for severe cases of shigellosis. Current drug therapies are under threat from the increasing rates of antibiotic resistance in Shigella serotypes around the world. The candidate vaccine, altSonflex1-2-3, has been evaluated for the FTiH in adults in Belgium, and is currently evaluated in a Phase 2 age de-escalation clinical study in Kenya, with the aim of identifying a preferred dose, using a 3-dose vaccinations schedule in infants from 9 months of age (NCT05073003). The current Phase 2 clinical study will evaluate the immunogenicity and safety of an alternative 2-dose vaccination schedule.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied Shigellosis
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 04/08/2024
Actual trial start date
Anticipated date of last follow up 12/06/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 200
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
2023 000945 18 EudraCT
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 Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group altSonflex1.2.3 vaccine low dose group Administration on days 1 and 169 Participants randomized to receive 2 doses if altSonflex1-2-3 low dose vaccine at days 1 and 169 with concomitant MR-VAC administration. 50
Experimental Group altSonflex1.2.3 vaccine middle dose group Administration on days 1 and 169 Participants randomized to receive 2 doses of altSonflex1-2-3 low dose vaccine at days 1 and 169 with concomitant MR-VAC administration. 50
Experimental Group altSonflex1.2.3 vaccine full dose group Administration on days 1 and 169 Participants randomized to receive 2 doses of altSonflex1-2-3 low dose vaccine at days 1 and 169 with concomitant MR-VAC administration. 50
Control Group Typhibev and Infanrix hexa group Administration on days 1 and 169 Participants will receive TYPHIBEV on Day 1 and Infanrix hexa on Day 169 with concomitant MR-VAC administration on both days. 50 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants are eligible to be included in the study only if all of the following criteria apply: • Participants’ parent(s)/LAR(s), who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits). • Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure. • Healthy participants as established by medical history, clinical examination, and laboratory assessment. • Participants satisfying all screening requirements. • Participants seronegative for hepatitis B, and hepatitis C. • A male or female 9 months of age at the time of the first study intervention administration. • Normal nutritional (weight-for-length) Z score (-2 standard deviations or greater). • Previously completed routine childhood vaccinations to the best knowledge of the participant’s parent(s)/LAR(s). • Born at a gestation period of ≥37 weeks to the best knowledge of the participant’s parent(s)/LAR(s). • Participants negative for human immunodeficiency virus as confirmed by DNA polymerase chain reaction testing. • Participants negative for HLA-B27. •History of any reaction or hypersensitivity associated with any component of the study interventions. •Any confirmed or suspected immunosuppressive or immunodeficient condition, •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality •Recurrent history or uncontrolled neurological disorders or seizures. •Any clinically significant hematological and/or biochemical laboratory abnormality. •Clinical conditions representing a contraindication to IM injections and/or blood draws. •Any behavioral or cognitive impairment or psychiatric disease that may interfere with the participant’s ability to participate in the study. •Confirmed positive COVID-19 from 28 days before the 1st dose •Acute or chronic illness which may be severe enough to preclude participation. •Any other clinical condition that, might pose additional risk to the participant due to participation in the study. •All medical conditions will be assessed by the Investigator who may use his/her discretion to decide if the participant meets the exclusion criteria. •Use of any investigational or non-registered product from (D−30 to 1) before the 1st dose of study interventions, or planned use during the study. •A vaccine not foreseen by the study protocol administered 14D pre 1st dose to 28D post last dose, with the exception of flu vaccines or COVID-19 vaccine. •Administration of long-acting immune-modifying drugs any time during the study period. •Administration of immunoglobulins and/or any blood products or plasma derivatives From 3Mo before 1st admin or throughout the study. •Chronic admin of immunosuppressants or other immune-modifying drugs from 3 Mo before 1st dose. •Prior receipt of an experimental Shigella vaccine or live Shigella challenge. •Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant’s parent(s)/LAR(s) or documented by participant’s records. •Child in care Infant: 0 Month-23 Month 9 Month(s) 9 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 18/12/2023 KEMRI Scientific and Ethics Review Unit SERU
Ethics Committee Address
Street address City Postal code Country
P.O. BOX 54840 00200 OFF MBAGATHI ROAD Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Anti-serotype-specific Shigella LPS/OAg* serum IgG GMCs/GMTs, as measured by ELISA, for each study intervention group. Before each study intervention administration on Day 1 and Day 169, and 28 days after each study intervention administration on Day 29 and Day 197
Primary Outcome Number of infants with at least a 4-fold increase in anti-serotypespecific Shigella LPS/OAg* serum IgG, as measured by ELISA, for each study intervention group. At 28 days after each study intervention administration Day 29 and Day 197, compared to baseline Day 1, and compared to pre-administration Day 1 and Day 169, respectively,
Secondary Outcome Number of infants with solicited administration-site events during the 7 days period after each study intervention administration On the day of study intervention administration and the 6 subsequent days, study intervention administration on Day 1 and Day 169
Secondary Outcome Number of infants with solicited systemic events during the 7 days period after each study intervention administration On the day of study intervention administration and the 6 subsequent day, study intervention administration on Day 1 and Day 169
Secondary Outcome Number of infants with SAEs during their entire study participation period From Day 1 to Day 197
Secondary Outcome Number of infants with deviations from laboratory reference values or baseline values of hematological, renal, and hepatic panel test results, at 7 days after each study intervention administration Day 8 and Day 176
Secondary Outcome Number of infants with unsolicited AEs during the 28 days period after each study intervention administration On the day of study intervention administration and the 27 subsequent days, study intervention administration on Day 1 and Day 169
Secondary Outcome Anti-measles IgG concentrations, as measured by ELISA Before the first MR-VAC Day 1 and at 28 days after the second MR-VAC vaccination Day 197
Secondary Outcome Anti-rubella IgG concentrations, as measured by ELISA Before the first MR-VAC on Day 1 and at 28 days after the second MR-VAC vaccination, Day 197
Secondary Outcome Number of infants achieving anti-measles IgG concentrations of ≥150 mIU/mL and ≥200 mIU/mL, as measured by ELISA 28 days after the second MR-VAC vaccination, Day 197
Secondary Outcome Number of infants achieving anti-rubella IgG concentrations of ≥4 IU/mL and ≥10 IU/mL, as measured by ELISA 28 days after the second MR-VAC vaccination, Day 197
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya Medical Research Institute KEMRI United States Army Medical Research Directorate Africa Kenya MRD A K Hospital Road, P.O. Box 1357 Kericho Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
GlaxoSmithKline Biologicals SA Rue De L Institut 89 Rixensart 1330 Belgium
Wellcome Trust 215 Euston Road London NW1 2BE United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor GlaxoSmithKline Biologicals SA Rue de l Institut 89 Rixensart 1330 Belgium Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Agnes Hunyady agnes.x.hunyady@gsk.com +393440996623 Via Fiorentina 1
City Postal code Country Position/Affiliation
Siena 53100 Italy Project Physician GSK Vaccines Institute for Global Health
Role Name Email Phone Street address
Principal Investigator Josphat Kosgei Josphat.kosgei@usamru-k.org +254522036100 KEMRI
City Postal code Country Position/Affiliation
Kericho Kenya Principal Research Investigator and Infectious Diseases Specialist at US Army Medical Research Unit
Role Name Email Phone Street address
Public Enquiries Leelgo Mary Kimetto leelgo.kimetto@usamru-k.org +254705251 Hospital Road PO Box 1357
City Postal code Country Position/Affiliation
Kericho Kenya Regulatory Officer
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK’s data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/ Supporting Materials: Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications. Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months. URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/ Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.clinicalstudydatarequest.com/Default.aspx 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