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Study to Expand Safety and Immunogenicity Data With Shigella Bioconjugate Vaccine (Shigella4V2) in 9-month-old Infants.

Phase 2
Not yet recruiting
Conditions
Shigellosis
Interventions
Biological: Shigella4V2
Biological: MenACWY
Registration Number
NCT06523231
Lead Sponsor
LimmaTech Biologics AG
Brief Summary

In this study, the second-generation tetravalent bioconjugate candidate vaccine Shigella4V2 will be tested to confirm data on its safety and immunogenicity in infants and to identify the best dose of Shigella4V2 in 9-month-old infants.

Detailed Description

Shigella4V2 is the second generation of a tetravalent bioconjugate vaccine including O-antigen-polysaccharides of the most predominant Shigella serotypes.

During the study, infants will be randomized to receive 1 of 2 different vaccine doses, or a control vaccine.

Participants will receive a 2-dose schedule. Each vaccine dose is formulated with Aluminium adjuvant.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
110
Inclusion Criteria
  • Female or male aged 9 months (± 1 month) old at the time of the first vaccination.
  • Born full-term (i.e., after a gestation period of 37 to less than 42 full weeks).
  • 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.
  • Seronegative for HIV, hepatitis B and C (as per screening laboratory tests)
  • Resident of Siaya County during the whole trial period.
  • 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.
  • 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.
  • 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).
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Exclusion Criteria
  • Any clinically significant deviation from the normal range in biochemistry or hematological 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 within 90 days prior to informed consent. Inhaled except for doses > 800 mg/day and topical steroids are allowed.
  • 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 study participant
  • 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 illness with or without fever is a temporary exclusion criterium. Positive malaria test is a temporary exclusion criterion.
  • History of any malignancy of lymphoproliferative disorder.
  • Parent/guardian 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.
  • Weight-for-age Z score less than -3 Standard Deviations (SD).
  • 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.
  • 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 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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
low doseShigella4V2Participants receive 2 low-dose administrations of the investigational product
high doseShigella4V2Participants receive 2 high-dose administrations of the investigational product
ControlMenACWYParticipants receive 2 administrations of MenACWY
Primary Outcome Measures
NameTimeMethod
Safety - Unsolicited Adverse Events (AEs)During 28 days following each vaccination

Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of unsolicited AEs

Safety - Serious Adverse Events (SAEs)Throughout the study, up to 9 months

Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of SAEs

Immunology - change in serum immunoglobulin G (IgG)From first vaccination until 1 month following the second vaccination

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.

Safety - Solicited Local and Systemic Adverse Events (AEs)During 7 days following each vaccination

Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of solicited AEs

Secondary Outcome Measures
NameTimeMethod
Immunogenicity - change in anti-Shigella lipopolysaccharide (LPS) antibody titersFrom first vaccination up to 1 month post 2nd vaccination

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.

Safety - clinically significant changes in creatinine levelFrom first vaccination until 7 days following each vaccination

Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters

Safety - clinically significant changes in aspartate aminotransferase (AST) levelFrom first vaccination until 7 days following each vaccination

Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters

Safety - clinically significant changes in alanine aminotransferase (ALT) levelFrom first vaccination until 7 days following each vaccination

Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters

Immunogenicity - persistence of serum IgGFrom first vaccination until 6 months post 2nd vaccination

Evaluation of geometric mean titers (GMT) for serum IgG against the four Shigella serotypes included in Shigella4V2 at 6 months post 2nd vaccination.

Safety - clinically significant changes in cell blood count (CBC) with differentialsFrom first vaccination until 7 days following each vaccination

Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in haematological safety parameters

Immunogenicity - change in serum IgGFrom first vaccination until 6 months post 2nd vaccination

Serum IgG responses and fold-increases between baseline and post-vaccination samples against the four Shigella serotypes included in the Shigella4V2 bioconjugate

Trial Locations

Locations (1)

KEMRI - Center for Global Health Research

🇰🇪

Kisumu, Kenya

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