A Study to Determine If a New Shigella Vaccine is Safe, Induces Immunity and The Best Dose Among Kenyan Infants

NCT ID: NCT04056117

Last Updated: 2024-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

596 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-02

Study Completion Date

2022-11-14

Brief Summary

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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

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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

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Shigellosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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NA (Non-adjuvanted) - very low dose - infants

Infants receive 3 very low doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - very low dose - infants

Infants receive 3 very low doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

NA (Non-adjuvanted) - low dose -infants

Infants receive 3 low doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - low dose - infants

Infants receive 3 low doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

NA (non-adjuvanted) - medium dose - infants

Infants receive 3 medium doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - medium dose - infants

Infants receive 3 medium doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

NA (non-adjuvanted) - medium dose - children

Children receive 3 medium doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - medium dose - children

Children receive 3 medium doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

NA (non-adjuvanted) - medium dose-adults

Adults receive 2 medium doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - medium dose - adults

Adults receive 2 medium doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

NA (non-adjuvanted) - high dose - infants

Infants receive 3 high doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - high dose - infants

Infants receive 3 high doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

NA (non-adjuvanted) - high dose - children

Chilldren receive 3 high doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - high dose - children

Chilldren receive 3 high doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

NA (non-adjuvanted) - high dose - adults

Adults receive 2 high doses of the non-adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

A (adjuvanted) - high dose - adults

Adults receive 2 high doses of the adjuvanted investigational product

Group Type EXPERIMENTAL

Shigella 4V

Intervention Type BIOLOGICAL

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

MenACWY-Placebo

Adults receive one administration of MenACWY followed by one placebo administration

Group Type EXPERIMENTAL

MenACWY

Intervention Type BIOLOGICAL

Control vaccine administrated to adults and infants

Placebo

Intervention Type BIOLOGICAL

Control administrated to adults

Rabies

Children receive three administrations of Rabies

Group Type OTHER

Rabies

Intervention Type BIOLOGICAL

Control vaccine administrated to children

MenACWY-DTaP

Infants receive two administrations of MenACWY followed by DTaP administration

Group Type OTHER

MenACWY

Intervention Type BIOLOGICAL

Control vaccine administrated to adults and infants

Diphtheria, Tetanus and Pertussis (DTaP)

Intervention Type BIOLOGICAL

Control vaccine administrated to infants

Interventions

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Shigella 4V

Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.

Intervention Type BIOLOGICAL

MenACWY

Control vaccine administrated to adults and infants

Intervention Type BIOLOGICAL

Rabies

Control vaccine administrated to children

Intervention Type BIOLOGICAL

Diphtheria, Tetanus and Pertussis (DTaP)

Control vaccine administrated to infants

Intervention Type BIOLOGICAL

Placebo

Control administrated to adults

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

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
* 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)

Exclusion Criteria

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.
* 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.
Minimum Eligible Age

8 Months

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Kenya Medical Research Institute

OTHER

Sponsor Role collaborator

KEMRI-Wellcome Trust Collaborative Research Program

OTHER

Sponsor Role collaborator

LimmaTech Biologics AG

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mainga Hamaluba, MD

Role: PRINCIPAL_INVESTIGATOR

KEMRI/Welcome Trust Research Programme,Kilifi, Kenya

Josphat Kosgei, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Research Institute, Kericho, Kenya

Locations

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Kenya Medical Research Institute (KEMRI)/ United States Army Medical Research Directorate- Kenya (USAMRD-K)

Kericho, , Kenya

Site Status

KEMRI-Centre Geographic Medical Research-COAST (KEMRI-CGMRC)

Kilifi, , Kenya

Site Status

Countries

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Kenya

References

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Taylor 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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Other Identifiers

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S4V01

Identifier Type: -

Identifier Source: org_study_id

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