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.: PACTR202208635693932 Date of Approval: 22/08/2022
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A study on the safety and immune responses to the GVGH altSonflex1-2-3 vaccine against shigellosis in adults, children, and infants
Official scientific title A staged Phase I/II observer-blind, randomised, controlled, multi-country study to evaluate the safety, reactogenicity, and immune responses to the GVGH altSonflex1-2-3 vaccine against S. sonnei and S. flexneri, serotypes 1b, 2a, and 3a, in adults in Europe (Stage 1) followed by age de-escalation from adults to children and infants, and dose-finding in infants in Africa (Stage 2)
Brief summary describing the background and objectives of the trial The aim of the current clinical study is to evaluate, for the first time in humans (FTIH), the safety and immunogenicity of the altSonflex1-2-3 candidate vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a. The vaccine will be first administered in adults 18 to 50 years of age in Europe. Subsequently, the vaccine will be administered to a shigellosis-endemic population in Africa, first in adults 18 to 50 years of age, then in children 24 to 59 months of age, and finally in infants 9 months of age. Infants will also receive a third vaccination. Three different doses of the vaccine [low (Dose A), medium (Dose B), and high (Dose C) amounts of antigen] will be evaluated using an age de-escalation approach (from least vulnerable adult population to most vulnerable paediatric population). The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Diarrhoeal disease due to Shigella infection
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 06/10/2021
Actual trial start date 06/10/2021
Anticipated date of last follow up 31/07/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 550
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 Central randomisation by phone/fax 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 altSonflex123dose C eu 2 doses at day 1 and day 85/169 in European adults Full dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a. 68
Control Group altSonflexplacebo 2 doses at day 1 and day 85/169 altSonflex Placebo, one each at Day 1 and Day 85 34 Placebo
Experimental Group altSonflex123dose C AF 2 doses at day 0 and day 85/169 in African adults Full dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a. 10
Control Group Boostrix Adult and menveo Menveo on day 1 and Boostrix on day 85 1 dose each Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine to African adults. Menveo is Neisseria meningitides A, C, W and Y 10 Active-Treatment of Control Group
Experimental Group altSonflex123dose C Africa child 2 doses at day 1 and 85 Full dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for children in Africa. 10
Experimental Group altSonflex123dose B Africa child 2 doses at day 1 and day 85 Medium dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for children in Africa. 10
Control Group Menveo and typhim Child Middle dose menveo at Day 1 and Typhim vi at day 85 1 dose each Meningococcal A, C, Y and W-135 conjugate vaccine and typhoid vi polysaccharide vaccines for children as comparators to middle dose 10 Active-Treatment of Control Group
Control Group Menveo and Typhim Vi Child Full dose Menveo at Day 1 and Typhim Vi at Day 85 1 dose each Meningococcal A, C, Y and W-135 conjugate vaccine and Typhoid Vi-polysaccharide vaccine for children as comparators to full dose 10 Active-Treatment of Control Group
Experimental Group altSonflex123 dose C Africa infant safety 3 doses at day 1, day 85 and day 253 Full dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for infants safety cohort in Africa. 10
Experimental Group altSonflex123 dose B Africa infant safety 3 doses at day 1, day 85 and day 253 Medium dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for children in Africa. 10
Experimental Group altSonflex123 dose A Africa infant safety 3 doses at day 1, day 85 and day 253 Low dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for children in Africa. 10
Control Group Menveo and infanrix Infant safety full dose 2 doses at day 1 and day 85 and infanrix at Day 253 2 doses and 1 dose Meningococcal A, C, Y and W-135 conjugate vaccine and Diphtheria, Tetanus and Acellular pertussis for infant safety cohort as comparator to full dose 10 Active-Treatment of Control Group
Control Group Menveo and Infanrix Infant safety medium dose 2 doses of menveo at Day 1 and Day 85 and Infanrix at Day 253 2 doses of menveo and 1 dose of infanrix Meningococcal A, C, Y and W-135 conjugate vaccine and Diphtheria, Tetanus and Acellular pertussis for infant safety cohort as comparator to medium dose 10 Active-Treatment of Control Group
Control Group Menveo Infant safety low dose 2 doses at day 1 and day 85 Meningococcal A, C, Y and W-135 conjugate vaccine for infant safety cohort as comparator to low dose 10 Active-Treatment of Control Group
Experimental Group altSonflex123 dose C Africa infant dose finding 3 doses at day 1, day 85 and day 253 Full dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for infants dose finding in Africa. 82
Experimental Group altSonflex123 dose B Africa infant dose finding 1 dose at day 1, day 85 and day 253 Medium dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for infants dose finding in Africa. 82
Experimental Group altSonflex123 dose A Africa infant dose finding 3 doses at day 1, day 85 and day 253 Low dose of the altSonflex GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a for infants dose finding in Africa 82
Control Group Menveo and Infanrix Infant dose finding 1 dose of Menveo at Day 1 and day 85 and Infanrix on Day 253 2 of Menveo and 1 dose of Infanrix Meningococcal A, C, Y and W-135 conjugate vaccine and Diphtheria, Tetanus and Acellular pertussis for infant dose-finding cohort as comparator 82 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
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 participant of non-childbearing potential may be enrolled in the study. • 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. • Participants negative for HIV as confirmed by DNA PCR testing All participants: • Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant or documented by patient records, recent travel* to a country where Shigella or other enteric infections are endemic, or recent occupation* involving Shigella species. *Limited to Adults 18 to 50 years of age in Europe. • Progressive, unstable or uncontrolled clinical conditions. • History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine. • Any confirmed or suspected immunosuppressive or immunodeficient condition. • 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. o 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. o Acute disease and/or fever at the time of enrolment* • Any clinically significant haematological and/or biochemical laboratory abnormality. o Confirmed positive COVID-19 test during the period starting 30 days before the first administration of study vaccines. o Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. o Administration of long-acting immune-modifying drugs at any time during the study period. o Prior receipt of an experimental Shigella vaccine or live Shigella challenge. o Use of any investigational or non-registered product* other than the study vaccine during the period. • Acute or chronic illness • Chronic administration of immunosuppressants or other immune-modifying drugs • Pregnant or lactating female • History of or current chronic alcohol consumption and/or drug abuse • Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplant Adult: 19 Year-44 Year,Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 9 Month(s) 50 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 30/09/2021 Commissie voor Medische Ethiek
Ethics Committee Address
Street address City Postal code Country
Univeritair Ziekenhuis Heymanslaan 10 Gent B 9000 Belgium
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 05/08/2022 Kenya Medical research Institute Scientific Ethics research Unit
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Anti-serotype specific Shigella lipopolysaccharide (LPS) serum immunoglobulin G (IgG) titers in infants 9 months of age in Africa At Day 281
Primary Outcome Number of adults 18 to 50 years of age with solicited systemic events Days 1 to 7 after each vaccination
Primary Outcome Number of adults 18 to 50 years of age with solicited administration site events Day 1 to 7 after each vaccination
Primary Outcome Number of adults 18 to 50 years of age with unsolicited adverse events Day 1 to 28 after each vaccination
Primary Outcome Number of adults 18 to 50 years of age with serious adverse events (SAEs) Entire study participation
Primary Outcome Number of adults 18 to 50 years of age with deviations from normal values of haematological, renal, and hepatic panel test results 7 days after each study intervention administration
Primary Outcome Number of children 24 to 59 months of age in Africa with solicited administration site events Day 1 to 7 after each vaccination
Primary Outcome Number of children 24 to 59 months of age in Africa with solicited systemic events Day 1 to 7 after each vaccination
Primary Outcome Number of children 24 to 59 months of age in Africa with unsolicited AEs Day 1 to 28 after each vaccination
Primary Outcome Number of children 24 to 59 months of age in Africa with SAEs Entire study participation
Primary Outcome Number of children 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results 7 days after each study intervention administration
Primary Outcome Number of infants 9 months of age in Africa with solicited administration site events Day 1 to 7 after each vaccination
Primary Outcome Number of infants 9 months of age in Africa with solicited systemic events Day 1 to 7 after each vaccination
Primary Outcome Number of infants 9 months of age in Africa with unsolicited AEs Day 1 to 28 after each vaccination
Primary Outcome Number of infants 9 months of age in Africa with SAEs Entire study participation
Primary Outcome Number of infants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results 7 days after each study intervention administration
Secondary Outcome Anti-serotype specific Shigella LPS/OAg serum IgG geometric mean concentrations (GMCs) in adults 18 to 50 years of age in Europe Day 1, 15, 29, 85/169 and 113/197
Secondary Outcome Anti-serotype specific Shigella LPS serum IgG GMTs in adults 18 to 50 years of age in Africa Day 1, 29, 85 and 113
Secondary Outcome Anti-serotype specific Shigella LPS serum IgG GMTs in children 24 to 59 months of age in Africa Day 1, 29, 85 and 113
Secondary Outcome Anti-serotype specific Shigella LPS serum IgG GMTs in infants 9 months of age in Africa Day 1, 29, 85, 113, 253 and 281
Secondary Outcome Number of adults 18 to 50 years of age in Europe achieving an ELISA level equivalent to ≥1:800 titer against S. sonnei LPS Day 1, 15, 29, 85/169 and 113/197
Secondary Outcome Number of adults 18 to 50 years of age in Africa achieving an ELISA level equivalent to ≥1:800 titer against S. sonnei LPS Day 1, 29, 85 and 113
Secondary Outcome Number of children 24 to 59 months of age in Africa achieving an ELISA level equivalent to ≥1:800 titer against S. sonnei LPS Day 1, 29, 85 and 113
Secondary Outcome Number of infants 9 months of age in Africa achieving an ELISA level equivalent to ≥1:800 titer against S. sonnei LPS Day 1, 29, 85, 113, 253 and 281
Secondary Outcome Number of adults 18 to 50 years of age in Europe achieving an ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS Day 1, 15, 29, 85/169, 113/197
Secondary Outcome Number of adults 18 to 50 years of age in Africa achieving an ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS Day 1, 29, 85 and 113
Secondary Outcome Number of children 24 to 59 months of age in Africa achieving an ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS Day 1, 29, 85 and 113
Secondary Outcome Number of infants 9 months of age in Africa achieving an ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS Day 1, 29, 85, 113, 253 and 281
Secondary Outcome 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 Day 1, 15, 29,85/169 and 113/197
Secondary Outcome 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 Day 1, 29,85 and 113
Secondary Outcome 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 Day 1, 29, 85 and 113
Secondary Outcome Number of infants 9 months of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS serum IgG titers Day 1, 29, 85, 113, 253 and 281
Secondary Outcome Anti-measles IgG concentrations in infants 9 months of age in the dose-finding groups in Africa Day 1 and 281
Secondary Outcome Anti-rubella IgG concentrations in infants 9 months of age in the dose-finding groups in Africa Day 1 and 281
Secondary Outcome Number of infants 9 months of age in the dose-finding groups in Africa achieving anti-measles IgG concentrations of ≥150 mIU/mL and ≥200 mIU/mL Day 1 and 281
Secondary Outcome Number of infants 9 months of age in the dose-finding groups in Africa achieving anti-rubella IgG concentrations of ≥4 IU/mL and ≥10 IU/mL Day 1 and 281
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centrum Voor Vaccinologie Universitair Ziekenhuis Gent, C. Heymanslaan 10 Gent 9000 Belgium
Kenya Medical research Institute KEMRI United States Army Medical Research Directorate Africa Kenya MRD AK Hospital Road, PO Box 1357 Kericho 20200 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 570 Mercer St Seattle WA 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor GlaxoSmithKline Biologicals Rue de lInstitut Rixensart 1330 Belgium Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
US Department of Defence Walter Reed Army Institute of Research 503 Robert Grant Avenue Silver Spring MD 2091 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Deborah Langat Deborah.langat@usamru-k.org +254522036100 Hospital Road, PO Box 1357
City Postal code Country Position/Affiliation
Kericho 20200 Kenya PI KEMRI WRAIR
Role Name Email Phone Street address
Scientific Enquiries Usman Nasir Nakakana usman.n.nakakana@gsk.com +393461152021 Via Fiorentina, 1
City Postal code Country Position/Affiliation
Siena 53100 Italy Senior project Physician GSK Vaccines Institute for Global Health
Role Name Email Phone Street address
Public Enquiries Charles Kilel Charles.kilel@usamru-k.org +254522036100 Hospital Road, PO Box 1357
City Postal code Country Position/Affiliation
Kericho Kenya Kenya Medical Research Institute United States Army Medical Research Directorate Africa Kenya
Role Name Email Phone Street address
Scientific Enquiries Deborah Langat Deborah.langat@usamru-k.org +254714059596 Hospital Road, PO Box 1357-20200
City Postal code Country Position/Affiliation
Kericho Kenya Kenya Medical Research Institute United States Army Medical Research Directorate Africa Kenya
Role Name Email Phone Street address
Scientific Enquiries Rita La Gaetana rita.x.la-gaetana@gsk.com +393401700275 Via Fiorentina, 1
City Postal code Country Position/Affiliation
Siena 53100 Italy Senior Regulatory Lead GSK Vaccines Institute for Global Health
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes IPD for this study will be made available via the Clinical Study Data Request site. 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