Prophylaxis for Shigellosis induced by Shigella sonnei, Shigella flexneri 1b, Shigella flexneri 2a and Shigella flexneri 3a. MedDRA version: 20.0 Level: HLT Classification code 10040550 Term: Shigella infections System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: PT Classification code 10054178 Term: Shigella infection System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: LLT Classification code 10040542 Term: Shigella System
Conditions
Interventions
Product Name: Shigella sonnei, Shigella flexneri 1b, 2a, 3a GMMA vaccine
Product Code: altSonflex1-2-3 (GSK4001785A)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Not applicable
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All participants: •Participants and/or participants’ parent(s)/legally acceptable representative(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 participant/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. •Participants negative for human leukocyte antigen B27 (HLA-B27). Adults 18 to 50 years of age: •A male or female between, and including, 18 and 50 years of age at the time of the first study intervention administration. •Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. •Female participants of childbearing potential may be enrolled in the study, if the participant: -has practiced adequate contraception for 1 month prior to study intervention administration, and -has a negative pregnancy test on the day of study intervention administration, and -has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series. •Participants seronegative for human immunodeficiency virus (HIV) Children 24 to 59 months of age: •A male or female between, and including, 24 and 59 months of age at the time of first vaccination. •Normal nutritional Z score (-2 standard deviation or greater) •Previously completed routine childhood vaccinations to the best knowledge of the participant’s parent(s)/LAR(s). •Born after gestation period of =37 weeks •Participants seronegative for HIV Infants 9 months of age: •A male or female 9 months of age at the time of first vaccination. •Normal nutritional 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 after a gestation period of =37 weeks •Participants negative for HIV as confirmed by deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing Are the trial subjects under 18? yes Number of subjects for this age range: 428 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 122 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: All participants: •Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant or documented by patient records (e.g., history of microbiologically-confirmed Shigella infection), recent travel* (within 2 years) to a s country where Shigella or other eneteric infections are endemic, or recent occupation* (within 3 years) involving Shigella species. •Progressive, unstable or uncontrolled clinical conditions. •History (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine. •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). •Hypersensitivity, including allergy, to medicinal products or medical equipment whose use is foreseen in this study. •Clinical conditions representing a contraindication to IM vaccination and blood draws. •Any behavioural or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant’s ability to participate in the study. •Acute disease and/or fever (defined as temperature ?38.0°C) at the time of enrolment*. *The participant can still be enrolled into the study at a time when the acute disease and/or fever has resolved. •Any clinically significant haematological and/or biochemical laboratory abnormality. •Confirmed positive COVID-19 test during the period starting 30 days before the first administration of study vaccines (Day -30 to Day 1) •Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. •Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). •Prior receipt of an experimental Shigella vaccine or live Shigella challenge. •Use of any investigational or non-registered product (drug, vaccine or medical device)* other than the study vaccine during the period starting 30 days before the first dose of study intervention (Day -30 to Day 1), or planned use during the study period. *Use of herbs and traditional treatments is not considered an exclusion criterion •A vaccine not foreseen* by the Study Protocol administered during the period starting at -21 days before the first dose (-28 days in the case of live vaccines) and ending after the last dose of study intervention administration**. •Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug or invasive medical device). •Any study personnel or immediate dependents, family, or household member. Adults 18 to 50 years of age: •Acute or chronic illness, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. •Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, during the period starting 3 months before the first dose of study vaccine or planned administration during the study period. •Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine study intervention. For corticosteroids, this will mean prednisone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To identify the preferred dose of each component of the altSonflex1-2-3 vaccine (low, medium, or high) for infants 9 months of age in Africa (Stage 2). • To evaluate the safety and reactogenicity of the altSonflex1-2-3 vaccine in all participants in Europe and Africa (Stage 1 and Stage 2). ;Secondary Objective: • To evaluate the immunogenicity profile of the altSonflex1-2-3 vaccine in all participants in Europe (Stage 1). • To evaluate the immunogenicity profile of the altSonflex1-2-3 vaccine in all participants in Africa (Stage 2). • To further characterise the immunogenicity profile of the S. sonnei component of altSonflex1-2-3 vaccine in all participants in Europe and Africa (Stage 1 and Stage 2). • To evaluate seroresponse with the altSonflex1-2-3 vaccine after each vaccination in all participants in Europe and Africa (Stage 1 and Stage 2). • To evaluate the immunogenicity of co-administered MR-VAC in infants 9 months of age in Africa (Stage 2), in the dose-finding cohort.;Primary end point(s): A. Anti-serotype specific Shigella lipopolysaccharide (LPS) serum immunoglobulin G (IgG) titers in infants 9 months of age in Africa B. Number of adults 18 to 50 years of age in Europe with solicited administration site events C. Number of adults 18 to 50 years of age in Europe with solicited systemic events D. Number of adults 18 to 50 years of age in Europe with unsolicited adverse events (AEs) E. Number of adults 18 to 50 years of age in Europe with serious adverse events (SAEs) F. Number of adults 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results at Day 8 G. Number of adults 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results at Day 92/Day 176 H. Number of adults 18 to 50 years of age in Africa with solicited administration site events I. Number of adults 18 to 50 years of age in Africa with solicited s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A.Anti-serotype specific Shigella LPS/OAg serum IgG geometric mean concentrations (GMCs) in adults 18 to 50 years of age in Europe B. Anti-serotype specific Shigella LPS serum IgG GMTs in adults 18 to 50 years of age in Africa C. Anti-serotype specific Shigella LPS serum IgG GMTs in children 24 to 59 months of age in Africa D. Anti-serotype specific Shigella LPS serum IgG GMTs in infants 9 months of age in Africa E. Number of adults 18 to 50 years of age in Europe achieving an ELISA level equivalent to =1:800 titer against S. sonnei LPS F. Number of adults 18 to 50 years of age in Africa achieving an ELISA level equivalent to =1:800 titer against S. sonnei LPS G. Number of children 24 to 59 months of age in Africa achieving an ELISA level equivalent to =1:800 titer against S. sonnei LPS H. Number of infants 9 months of age in Africa achieving an ELISA level equivalent to =1:800 titer against S. sonnei LPS I.Number of adults 18 to 50 years of age in Europe achieving an ELISA level equivalent to =1:1600 titer against S. sonnei LPS J. Number of adults 18 to 50 years of age in Africa achieving an ELISA level equivalent to =1:1600 titer against S. sonnei LPS K. Number of children 24 to 59 months of age in Africa achieving an ELISA level equivalent to =1:1600 titer against S. sonnei LPS L. Number of infants 9 months of age in Africa achieving an ELISA level equivalent to =1:1600 titer against S. sonnei LPS M. Number of adults 18 to 50 years of age in Europe showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations N. Number of adults 18 to 50 years of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS serum IgG titers O. Number of children 24 to 59 months of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS serum IgG titers P. Number of infants 9 months of age in Africa showing at least a 4-fold increase in anti-ser | — |
Countries
Belgium, Kenya
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed