ShigellosisPhase 1/2NCT04056117
A Study to Determine If a New Shigella Vaccine is Safe, Induces Immunity and The Best Dose Among Kenyan Infants
A Phase 1/2 study testing Shigella 4V, MenACWY and Rabies in people with Shigellosis, run by LimmaTech Biologics AG at 2 sites in Kenya.
Trial summary
In this study, the tetravalent bioconjugate candidate vaccine Shigella4V will be tested to obtain first-in-human data on its safety and immunogenicity in infants and to identify the preferred dose of Shigella4V in 9 month old infants. Read more about this study
- Who is it for?
- Ages 8 months to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigellosis
- What is being tested?
- Shigella 4V, MenACWY and Rabies
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 597 participants
- Where
- 2 sitesKenya
- Study dates
- 2 Sep 2019to 14 Nov 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 months to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- All ages
- Healthy by medical history, laboratory findings and physical examination before entering into the study (Participants with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator)
- Seronegative for HIV, hepatitis B and C (as per screening laboratory tests)
- Resident in the study area village during the whole trial period (Kilifi -Kilifi Health and Demographic Surveillance System (Described in more detail in the SSA); (Kericho-a 75km radius from the Kericho Clinical Research Centre).
- Previously completed routine primary vaccinations (6,10 and 14 weeks or thereabouts) to the best knowledge of the participant/parent/guardian.
- Signed/thumb written informed consent, in accordance with local practice, provided by adult volunteers (participants 18 years of age and older), parents or legal representatives for children and infants participants as applicable, who, in the opinion of the investigator, can and will comply with the requirements of the protocol
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- Demonstrated comprehension of the protocol procedures by passing score of 90% or better on a written/verbal comprehension test.
- Adults
- Female and male participants between, and including 18-50 years at the time of first vaccination
- 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 volunteers of childbearing potential may be enrolled in the study if the participant: has a negative urine pregnancy test at the day of screening and vaccinations, respectively, and
- agree to use effective contraception for 30 days prior to vaccination and
- agree to continue contraception at least for 2 months after completion of vaccination series.
- Children and Infants
- Female and male aged 9 months (+/- 1 month) old (infants) or between, and including, 2-5 years of age (children) at the time of the first vaccination
- Born full-term (i.e. after a gestation period of 37 to less than 42 completed weeks)
Who cannot join
- All ages
- Any clinically significant deviation from the normal range in biochemistry or haematological blood tests.
- 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
- Clinical conditions representing a contraindication to intramuscular vaccination and blood draws
- Any confirmed or suspected immunosuppressive or immune-deficient condition.
- Systemic administration of corticosteroids (PO/IV/IM): prednisone ≥20 mg/day, or equivalent for more than 14 consecutive days from birth (for infants) / within 90 days prior to informed consent. Inhaled except for doses > 800 mg/day and topical steroids are allowed.
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- 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
- Known exposure to Shigella during lifetime of the subject
- 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)
- Acute disease and /or fever at the time of enrolment Note: enrolment may be postponed/delayed until such transient circumstances have terminated
- History of any malignancy of lymphoproliferative disorder
- Known to be part of study personnel or being a close family member to the personnel conducting this study.
- Previous history of significant persistent neutropenia, or drug related Neutropenia
- Adults with clinical wasting; children with weight-for-age Z score less than -3SD.
- History of any chronic or progressive disease (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease) that according to judgment of the investigator could interfere with the study outcomes or pose a threat to the participant's health
- History of surgical splenectomy or Sickle cell disease (SCD test performed at KEMRI-CGMRC only).
- Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine
- Any medical, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's/parent's/guardian's ability to give informed consent, increases the risk to the potential participant because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data .
- Adults
- Women who are breastfeeding
- History of chronic alcohol consumption and/or drug abuse. Chronic alcohol consumption is defined as: a prolonged period of frequent, heavy alcohol use; the inability to control drinking once it has begun; physical dependence manifested by withdrawal symptoms when the individual stops using alcohol; tolerance, or the need to use more and more alcohol to achieve the same effects; a variety of social and/or legal problems arising from alcohol use.
Trial locations and contacts
2 sites in 1 country.
Kenya2 sites
Kenya Medical Research Institute (KEMRI)/ United States Army Medical Research Directorate- Kenya (USAMRD-K)
Kericho, 1357-20200
KEMRI-Centre Geographic Medical Research-COAST (KEMRI-CGMRC)
Kilifi, 230-80108
About this study
Official title: Safety and Immunogenicity of a Shigella-Tetravalent Bioconjugate Vaccine: A Phase 1/2 Randomized Controlled and Age Descending Study Including Dose Finding in 9 Month Old Infants
In this study, the tetravalent bioconjugate candidate vaccine Shigella4V will be tested to obtain first-in-human data on its safety and immunogenicity in infants and to identify the preferred dose of Shigella4V in 9 month old infants.
Read the detailed description
Shigella4V is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Shigella serotypes.
The study will be conducted in two steps. In Step1: safety and reactogenicity of the vaccine will be evaluated first in adults and subsequently in children and infants through an age-descending and dose escalation approach. In Step 2: in order to further evaluate safety and to identify the optimum immunogenic dose, infants will be randomised to receive 1 of 4 different vaccine doses or control vaccine.
Adults will receive a 2 dose schedule, children and infants will receive a 3 dose schedule. For each vaccine dose, formulation with and without Aluminium adjuvant will be tested.
- Conditions
- Shigellosis
- Being tested
- Shigella 4V, MenACWY, Rabies, Diphtheria, Tetanus and Pertussis (DTaP), Placebo
- Medical subject headings
- Dysentery, Bacillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Shigella 4VBiological
Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.
MenACWYBiological
Control vaccine administrated to adults and infants
RabiesBiological
Control vaccine administrated to children
Diphtheria, Tetanus and Pertussis (DTaP)Biological
Control vaccine administrated to infants
PlaceboBiological
Control administrated to adults
| Study group | Role | What they receive |
|---|---|---|
| NA (Non-adjuvanted) - very low dose - infants | Experimental | Infants receive 3 very low doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - very low dose - infants | Experimental | Infants receive 3 very low doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| NA (Non-adjuvanted) - low dose -infants | Experimental | Infants receive 3 low doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - low dose - infants | Experimental | Infants receive 3 low doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| NA (non-adjuvanted) - medium dose - infants | Experimental | Infants receive 3 medium doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - medium dose - infants | Experimental | Infants receive 3 medium doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| NA (non-adjuvanted) - medium dose - children | Experimental | Children receive 3 medium doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - medium dose - children | Experimental | Children receive 3 medium doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| NA (non-adjuvanted) - medium dose-adults | Experimental | Adults receive 2 medium doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - medium dose - adults | Experimental | Adults receive 2 medium doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| NA (non-adjuvanted) - high dose - infants | Experimental | Infants receive 3 high doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - high dose - infants | Experimental | Infants receive 3 high doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| NA (non-adjuvanted) - high dose - children | Experimental | Chilldren receive 3 high doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - high dose - children | Experimental | Chilldren receive 3 high doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| NA (non-adjuvanted) - high dose - adults | Experimental | Adults receive 2 high doses of the non-adjuvanted investigational product Receives: Biological: Shigella 4V |
| A (adjuvanted) - high dose - adults | Experimental | Adults receive 2 high doses of the adjuvanted investigational product Receives: Biological: Shigella 4V |
| MenACWY-Placebo | Experimental | Adults receive one administration of MenACWY followed by one placebo administration Receives: Biological: MenACWY; Biological: Placebo |
| Rabies | Other | Children receive three administrations of Rabies Receives: Biological: Rabies |
| MenACWY-DTaP | Other | Infants receive two administrations of MenACWY followed by DTaP administration Receives: Biological: MenACWY; Biological: Diphtheria, Tetanus and Pertussis (DTaP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Solicited Local and Systemic Adverse Events (AEs)
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of solicited AEs
Measured: during 7 days following each vaccination
Safety - Unsolicited Adverse Events (AEs)
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of unsolicited AEs
Measured: during 28 days following each vaccination
Safety - Serious Adverse Events (SAEs)
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of SAEs
Measured: throughout the study duration, up to 15 months
Immunology - change in serum immunoglobulin G (IgG)
Serum IgG responses and fold-increases between post- and pre-vaccination samples from infants of step 2, as determined by enzyme-linked immunosorbent assay (ELISA) against lipopolysaccharide (LPS) corresponding to the 4 Shigella serotypes included in the Shigella4V bioconjugate.
Measured: throughout the study, up to 15 months
Secondary outcomes (6)
Safety - clinically significant changes in cell blood count (CBC) with differentials
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in haematological safety parameters
Measured: throughout the study, up to 15 months
Safety - clinically significant changes in creatinine level
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters
Measured: throughout the study, up to 15 months
Safety - clinically significant changes in alanine aminotransferase (ALT) level
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters
Measured: throughout the study, up to 15 months
Safety - clinically significant changes in aspartate aminotransferase (AST) level
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters
Measured: throughout the study, up to 15 months
Immunogenicity - change is serum IgG
Serum IgG responses and fold-increases between post- and pre-vaccination samples from all participants of step 1, as determined by ELISA against LPS corresponding to the 4 Shigella serotypes included in the Shigella4V bioconjugate.
Measured: throughout the study, up to 15 months
Immunogenicity - change in anti-Shigella LPS antibody titre
Percentage of participants (from step 1 and 2) achieving at least a four-fold rise in anti-Shigella LPS antibody titre after each injection compared to baseline.
Measured: throughout the study, up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2019
- Study start2 Sep 2019
- Primary completion1 Sep 2022
- Study completion14 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for ShigellosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This phase 1/2 trial is a multicentre, randomized, controlled, double blind, with two steps; a step 1 with a safety cohort and a step 2 with a dose-finding cohort. Safety of the vaccine will be evaluated first in adults and subsequently in children and infants through an age-descending and dose escalation approach (safety cohort, step 1). Following confirmation of vaccine safety, further cohorts of infants (dose-finding cohort) will be enrolled to evaluate immunogenicity of the vaccine at different doses and expand safety data (step 2). Vaccination in Step 1 will be staggered with adults being the first to be vaccinated and infants last. In step 2 infants will be vaccinated concurrently, with each group randomised to receive 1 of 4 different vaccine doses. A control vaccine will be used, and participants will be randomized at a ratio of 3:1 in adults, 2:1 in children, 2:1 in infants in step 1 and 8:1 in infants in step 2, to receive the candidate vaccine versus the control vaccine.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 597 participants (actual)
Sponsor and investigators
- Lead sponsor
- LimmaTech Biologics AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kenya Medical Research Institute, KEMRI-Wellcome Trust Collaborative Research Program
- Responsible party
- Sponsor
- Investigators
- Mainga Hamaluba, MD, Principal investigator, KEMRI/Welcome Trust Research Programme,Kilifi, KenyaJosphat Kosgei, MD, Principal investigator, Medical Research Institute, Kericho, Kenya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04056117
- Sponsor's protocol ID
- S4V01
- Status last verified
- Jun 2026
- First submitted
- 26 Jul 2019
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
GBD 2015 LRI Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis. 2017 Nov;17(11):1133-1161. doi: 10.1016/S1473-3099(17)30396-1. Epub 2017 Aug 23.
PubMed 28843578Livio S, Strockbine NA, Panchalingam S, Tennant SM, Barry EM, Marohn ME, Antonio M, Hossain A, Mandomando I, Ochieng JB, Oundo JO, Qureshi S, Ramamurthy T, Tamboura B, Adegbola RA, Hossain MJ, Saha D, Sen S, Faruque AS, Alonso PL, Breiman RF, Zaidi AK, Sur D, Sow SO, Berkeley LY, O'Reilly CE, Mintz ED, Biswas K, Cohen D, Farag TH, Nasrin D, Wu Y, Blackwelder WC, Kotloff KL, Nataro JP, Levine MM. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis. 2014 Oct;59(7):933-41. doi: 10.1093/cid/ciu468. Epub 2014 Jun 23.
PubMed 24958238Mani S, Wierzba T, Walker RI. Status of vaccine research and development for Shigella. Vaccine. 2016 Jun 3;34(26):2887-2894. doi: 10.1016/j.vaccine.2016.02.075. Epub 2016 Mar 12.
PubMed 26979135Ashkenazi S, Cohen D. An update on vaccines against Shigella. Ther Adv Vaccines. 2013 Sep;1(3):113-23. doi: 10.1177/2051013613500428.
PubMed 24757519Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013 Jul 20;382(9888):209-22. doi: 10.1016/S0140-6736(13)60844-2. Epub 2013 May 14.
PubMed 23680352Anderson M, Sansonetti PJ, Marteyn BS. Shigella Diversity and Changing Landscape: Insights for the Twenty-First Century. Front Cell Infect Microbiol. 2016 Apr 19;6:45. doi: 10.3389/fcimb.2016.00045. eCollection 2016.
PubMed 27148494Kotloff KL, Platts-Mills JA, Nasrin D, Roose A, Blackwelder WC, Levine MM. Global burden of diarrheal diseases among children in developing countries: Incidence, etiology, and insights from new molecular diagnostic techniques. Vaccine. 2017 Dec 14;35(49 Pt A):6783-6789. doi: 10.1016/j.vaccine.2017.07.036. Epub 2017 Jul 29.
PubMed 28765005Juergens C, de Villiers PJ, Moodley K, Jayawardene D, Jansen KU, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine formulations with and without aluminum phosphate and comparison of the formulation of choice with 23-valent pneumococcal polysaccharide vaccine in elderly adults: a randomized open-label trial. Hum Vaccin Immunother. 2014;10(5):1343-53. doi: 10.4161/hv.27998. Epub 2014 Feb 27.
PubMed 24576885Bryant K, McVernon J, Marchant C, Nolan T, Marshall G, Richmond P, Marshall H, Nissen M, Lambert S, Aris E, Mesaros N, Miller J. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. Hum Vaccin Immunother. 2012 Aug;8(8):1036-41. doi: 10.4161/hv.20357. Epub 2012 Aug 1.
PubMed 22617844Miller E, Andrews N, Waight P, Findlow H, Ashton L, England A, Stanford E, Matheson M, Southern J, Sheasby E, Goldblatt D, Borrow R. Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age. Clin Vaccine Immunol. 2011 Mar;18(3):367-72. doi: 10.1128/CVI.00516-10. Epub 2010 Dec 29.
PubMed 21191076Taylor DN, Trofa AC, Sadoff J, Chu C, Bryla D, Shiloach J, Cohen D, Ashkenazi S, Lerman Y, Egan W, et al. Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids. Infect Immun. 1993 Sep;61(9):3678-87. doi: 10.1128/iai.61.9.3678-3687.1993.
PubMed 8359890Ashkenazi S, Passwell JH, Harlev E, Miron D, Dagan R, Farzan N, Ramon R, Majadly F, Bryla DA, Karpas AB, Robbins JB, Schneerson R. Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children. J Infect Dis. 1999 Jun;179(6):1565-8. doi: 10.1086/314759.
PubMed 10228084
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Immunogenicity of a Shigella-Tetravalent Bioconjugate Vaccine: A Phase 1/2 Randomized Controlled and Age Descending Study Including Dose Finding in 9 Month Old Infants
- ClinicalTrials.gov ID
- NCT04056117
- Acronym / sponsor ID
- S4V01
- Conditions
- Shigellosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 597 participants (actual)
- Lead sponsor
- LimmaTech Biologics AGIndustry (pharma, biotech, devices)
- Collaborators
- Kenya Medical Research Institute, KEMRI-Wellcome Trust Collaborative Research Program
- Study start
- 2 Sep 2019 (actual)
- Primary completion
- 1 Sep 2022 (actual)
- Study completion
- 14 Nov 2022 (actual)
- First posted
- 14 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, the tetravalent bioconjugate candidate vaccine Shigella4V will be tested to obtain first-in-human data on its safety and immunogenicity in infants and to identify the preferred dose of Shigella4V in 9 month old infants.
Detailed description
Shigella4V is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Shigella serotypes.
The study will be conducted in two steps. In Step1: safety and reactogenicity of the vaccine will be evaluated first in adults and subsequently in children and infants through an age-descending and dose escalation approach. In Step 2: in order to further evaluate safety and to identify the optimum immunogenic dose, infants will be randomised to receive 1 of 4 different vaccine doses or control vaccine.
Adults will receive a 2 dose schedule, children and infants will receive a 3 dose schedule. For each vaccine dose, formulation with and without Aluminium adjuvant will be tested.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 19
- Model description
- This phase 1/2 trial is a multicentre, randomized, controlled, double blind, with two steps; a step 1 with a safety cohort and a step 2 with a dose-finding cohort. Safety of the vaccine will be evaluated first in adults and subsequently in children and infants through an age-descending and dose escalation approach (safety cohort, step 1). Following confirmation of vaccine safety, further cohorts of infants (dose-finding cohort) will be enrolled to evaluate immunogenicity of the vaccine at different doses and expand safety data (step 2). Vaccination in Step 1 will be staggered with adults being the first to be vaccinated and infants last. In step 2 infants will be vaccinated concurrently, with each group randomised to receive 1 of 4 different vaccine doses. A control vaccine will be used, and participants will be randomized at a ratio of 3:1 in adults, 2:1 in children, 2:1 in infants in step 1 and 8:1 in infants in step 2, to receive the candidate vaccine versus the control vaccine.
| Arm | Type | Receives |
|---|---|---|
| NA (Non-adjuvanted) - very low dose - infants | Experimental | Biological: Shigella 4VInfants receive 3 very low doses of the non-adjuvanted investigational product |
| A (adjuvanted) - very low dose - infants | Experimental | Biological: Shigella 4VInfants receive 3 very low doses of the adjuvanted investigational product |
| NA (Non-adjuvanted) - low dose -infants | Experimental | Biological: Shigella 4VInfants receive 3 low doses of the non-adjuvanted investigational product |
| A (adjuvanted) - low dose - infants | Experimental | Biological: Shigella 4VInfants receive 3 low doses of the adjuvanted investigational product |
| NA (non-adjuvanted) - medium dose - infants | Experimental | Biological: Shigella 4VInfants receive 3 medium doses of the non-adjuvanted investigational product |
| A (adjuvanted) - medium dose - infants | Experimental | Biological: Shigella 4VInfants receive 3 medium doses of the adjuvanted investigational product |
| NA (non-adjuvanted) - medium dose - children | Experimental | Biological: Shigella 4VChildren receive 3 medium doses of the non-adjuvanted investigational product |
| A (adjuvanted) - medium dose - children | Experimental | Biological: Shigella 4VChildren receive 3 medium doses of the adjuvanted investigational product |
| NA (non-adjuvanted) - medium dose-adults | Experimental | Biological: Shigella 4VAdults receive 2 medium doses of the non-adjuvanted investigational product |
| A (adjuvanted) - medium dose - adults | Experimental | Biological: Shigella 4VAdults receive 2 medium doses of the adjuvanted investigational product |
| NA (non-adjuvanted) - high dose - infants | Experimental | Biological: Shigella 4VInfants receive 3 high doses of the non-adjuvanted investigational product |
| A (adjuvanted) - high dose - infants | Experimental | Biological: Shigella 4VInfants receive 3 high doses of the adjuvanted investigational product |
| NA (non-adjuvanted) - high dose - children | Experimental | Biological: Shigella 4VChilldren receive 3 high doses of the non-adjuvanted investigational product |
| A (adjuvanted) - high dose - children | Experimental | Biological: Shigella 4VChilldren receive 3 high doses of the adjuvanted investigational product |
| NA (non-adjuvanted) - high dose - adults | Experimental | Biological: Shigella 4VAdults receive 2 high doses of the non-adjuvanted investigational product |
| A (adjuvanted) - high dose - adults | Experimental | Biological: Shigella 4VAdults receive 2 high doses of the adjuvanted investigational product |
| MenACWY-Placebo | Experimental | Biological: MenACWY, Biological: PlaceboAdults receive one administration of MenACWY followed by one placebo administration |
| Rabies | Other | Biological: RabiesChildren receive three administrations of Rabies |
| MenACWY-DTaP | Other | Biological: MenACWY, Biological: Diphtheria, Tetanus and Pertussis (DTaP)Infants receive two administrations of MenACWY followed by DTaP administration |
Who may qualify
- Ages
- 8 months to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- All ages
- Healthy by medical history, laboratory findings and physical examination before entering into the study (Participants with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator)
- Seronegative for HIV, hepatitis B and C (as per screening laboratory tests)
- Resident in the study area village during the whole trial period (Kilifi -Kilifi Health and Demographic Surveillance System (Described in more detail in the SSA); (Kericho-a 75km radius from the Kericho Clinical Research Centre).
- Previously completed routine primary vaccinations (6,10 and 14 weeks or thereabouts) to the best knowledge of the participant/parent/guardian.
Key exclusion criteria (21 listed)
- All ages
- Any clinically significant deviation from the normal range in biochemistry or haematological blood tests.
- 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
- Clinical conditions representing a contraindication to intramuscular vaccination and blood draws
- Any confirmed or suspected immunosuppressive or immune-deficient condition.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Shigella 4VNon-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high. | Biological | A (adjuvanted) - high dose - adults, A (adjuvanted) - high dose - children, A (adjuvanted) - high dose - infants, A (adjuvanted) - low dose - infants, A (adjuvanted) - medium dose - adults, A (adjuvanted) - medium dose - children, A (adjuvanted) - medium dose - infants, A (adjuvanted) - very low dose - infants, NA (Non-adjuvanted) - low dose -infants, NA (Non-adjuvanted) - very low dose - infants, NA (non-adjuvanted) - high dose - adults, NA (non-adjuvanted) - high dose - children, NA (non-adjuvanted) - high dose - infants, NA (non-adjuvanted) - medium dose - children, NA (non-adjuvanted) - medium dose - infants, NA (non-adjuvanted) - medium dose-adults |
| MenACWYControl vaccine administrated to adults and infants | Biological | MenACWY-DTaP, MenACWY-Placebo |
| RabiesControl vaccine administrated to children | Biological | Rabies |
| Diphtheria, Tetanus and Pertussis (DTaP)Control vaccine administrated to infants | Biological | MenACWY-DTaP |
| PlaceboControl administrated to adults | Biological | MenACWY-Placebo |
Primary outcome
Safety - Solicited Local and Systemic Adverse Events (AEs)
Time frame: during 7 days following each vaccination
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of solicited AEs
Safety - Unsolicited Adverse Events (AEs)
Time frame: during 28 days following each vaccination
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of unsolicited AEs
Safety - Serious Adverse Events (SAEs)
Time frame: throughout the study duration, up to 15 months
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of SAEs
Immunology - change in serum immunoglobulin G (IgG)
Time frame: throughout the study, up to 15 months
Serum IgG responses and fold-increases between post- and pre-vaccination samples from infants of step 2, as determined by enzyme-linked immunosorbent assay (ELISA) against lipopolysaccharide (LPS) corresponding to the 4 Shigella serotypes included in the Shigella4V bioconjugate.
6 secondary outcomes
Safety - clinically significant changes in cell blood count (CBC) with differentials
Time frame: throughout the study, up to 15 months
Safety - clinically significant changes in creatinine level
Time frame: throughout the study, up to 15 months
Safety - clinically significant changes in alanine aminotransferase (ALT) level
Time frame: throughout the study, up to 15 months
Safety - clinically significant changes in aspartate aminotransferase (AST) level
Time frame: throughout the study, up to 15 months
Immunogenicity - change is serum IgG
Time frame: throughout the study, up to 15 months
Immunogenicity - change in anti-Shigella LPS antibody titre
Time frame: throughout the study, up to 15 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Background: PubMed 28843578GBD 2015 LRI Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis. 2017 Nov;17(11):1133-1161. doi: 10.1016/S1473-3099(17)30396-1. Epub 2017 Aug 23.
- Background: PubMed 24958238Livio S, Strockbine NA, Panchalingam S, Tennant SM, Barry EM, Marohn ME, Antonio M, Hossain A, Mandomando I, Ochieng JB, Oundo JO, Qureshi S, Ramamurthy T, Tamboura B, Adegbola RA, Hossain MJ, Saha D, Sen S, Faruque AS, Alonso PL, Breiman RF, Zaidi AK, Sur D, Sow SO, Berkeley LY, O'Reilly CE, Mintz ED, Biswas K, Cohen D, Farag TH, Nasrin D, Wu Y, Blackwelder WC, Kotloff KL, Nataro JP, Levine MM. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis. 2014 Oct;59(7):933-41. doi: 10.1093/cid/ciu468. Epub 2014 Jun 23.
- Background: PubMed 26979135Mani S, Wierzba T, Walker RI. Status of vaccine research and development for Shigella. Vaccine. 2016 Jun 3;34(26):2887-2894. doi: 10.1016/j.vaccine.2016.02.075. Epub 2016 Mar 12.
- Background: PubMed 24757519Ashkenazi S, Cohen D. An update on vaccines against Shigella. Ther Adv Vaccines. 2013 Sep;1(3):113-23. doi: 10.1177/2051013613500428.
- Background: PubMed 23680352Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013 Jul 20;382(9888):209-22. doi: 10.1016/S0140-6736(13)60844-2. Epub 2013 May 14.
- Background: PubMed 27148494Anderson M, Sansonetti PJ, Marteyn BS. Shigella Diversity and Changing Landscape: Insights for the Twenty-First Century. Front Cell Infect Microbiol. 2016 Apr 19;6:45. doi: 10.3389/fcimb.2016.00045. eCollection 2016.
- Background: PubMed 28765005Kotloff KL, Platts-Mills JA, Nasrin D, Roose A, Blackwelder WC, Levine MM. Global burden of diarrheal diseases among children in developing countries: Incidence, etiology, and insights from new molecular diagnostic techniques. Vaccine. 2017 Dec 14;35(49 Pt A):6783-6789. doi: 10.1016/j.vaccine.2017.07.036. Epub 2017 Jul 29.
- Background: PubMed 24576885Juergens C, de Villiers PJ, Moodley K, Jayawardene D, Jansen KU, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine formulations with and without aluminum phosphate and comparison of the formulation of choice with 23-valent pneumococcal polysaccharide vaccine in elderly adults: a randomized open-label trial. Hum Vaccin Immunother. 2014;10(5):1343-53. doi: 10.4161/hv.27998. Epub 2014 Feb 27.
- Background: PubMed 22617844Bryant K, McVernon J, Marchant C, Nolan T, Marshall G, Richmond P, Marshall H, Nissen M, Lambert S, Aris E, Mesaros N, Miller J. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. Hum Vaccin Immunother. 2012 Aug;8(8):1036-41. doi: 10.4161/hv.20357. Epub 2012 Aug 1.
- Background: PubMed 21191076Miller E, Andrews N, Waight P, Findlow H, Ashton L, England A, Stanford E, Matheson M, Southern J, Sheasby E, Goldblatt D, Borrow R. Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age. Clin Vaccine Immunol. 2011 Mar;18(3):367-72. doi: 10.1128/CVI.00516-10. Epub 2010 Dec 29.
- Background: PubMed 8359890Taylor DN, Trofa AC, Sadoff J, Chu C, Bryla D, Shiloach J, Cohen D, Ashkenazi S, Lerman Y, Egan W, et al. Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids. Infect Immun. 1993 Sep;61(9):3678-87. doi: 10.1128/iai.61.9.3678-3687.1993.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mainga Hamaluba, MD principal investigator
KEMRI/Welcome Trust Research Programme,Kilifi, Kenya
Josphat Kosgei, MD principal investigator
Medical Research Institute, Kericho, Kenya
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Shigella 4V, MenACWY and Rabies in people with Shigellosis, run by LimmaTech Biologics AG at 2 sites in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety - Solicited Local and Systemic Adverse Events (AEs) (time frame: during 7 days following each vaccination). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04056117, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.