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

NCT04056117 | Completed Phase 1 DMC

• 1 other identifier: S4V01
• Study Type: interventional
• Target: 596
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Shigellosis

Outcome Measures

Primary Outcomes (4)

• 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

  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

  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

  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.

  throughout the study, up to 15 months

Secondary Outcomes (6)

• Safety - clinically significant changes in cell blood count (CBC) with differentials

  throughout the study, up to 15 months

• Safety - clinically significant changes in creatinine level

  throughout the study, up to 15 months

• Safety - clinically significant changes in alanine aminotransferase (ALT) level

  throughout the study, up to 15 months

• Safety - clinically significant changes in aspartate aminotransferase (AST) level

  throughout the study, up to 15 months

• Immunogenicity - change is serum IgG

  throughout the study, up to 15 months

Study Arms (19)

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

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - very low dose - infants

EXPERIMENTAL

Infants receive 3 very low doses of the adjuvanted investigational product

Biological: Shigella 4V

NA (Non-adjuvanted) - low dose -infants

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - low dose - infants

EXPERIMENTAL

Infants receive 3 low doses of the adjuvanted investigational product

Biological: Shigella 4V

NA (non-adjuvanted) - medium dose - infants

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - medium dose - infants

EXPERIMENTAL

Infants receive 3 medium doses of the adjuvanted investigational product

Biological: Shigella 4V

NA (non-adjuvanted) - medium dose - children

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - medium dose - children

EXPERIMENTAL

Children receive 3 medium doses of the adjuvanted investigational product

Biological: Shigella 4V

NA (non-adjuvanted) - medium dose-adults

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - medium dose - adults

EXPERIMENTAL

Adults receive 2 medium doses of the adjuvanted investigational product

Biological: Shigella 4V

NA (non-adjuvanted) - high dose - infants

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - high dose - infants

EXPERIMENTAL

Infants receive 3 high doses of the adjuvanted investigational product

Biological: Shigella 4V

NA (non-adjuvanted) - high dose - children

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - high dose - children

EXPERIMENTAL

Chilldren receive 3 high doses of the adjuvanted investigational product

Biological: Shigella 4V

NA (non-adjuvanted) - high dose - adults

EXPERIMENTAL

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

Biological: Shigella 4V

A (adjuvanted) - high dose - adults

EXPERIMENTAL

Adults receive 2 high doses of the adjuvanted investigational product

Biological: Shigella 4V

MenACWY-Placebo

EXPERIMENTAL

Adults receive one administration of MenACWY followed by one placebo administration

Biological: MenACWY; Biological: Placebo

Rabies

OTHER

Children receive three administrations of Rabies

Biological: Rabies

MenACWY-DTaP

OTHER

Infants receive two administrations of MenACWY followed by DTaP administration

Biological: MenACWY; Biological: Diphtheria, Tetanus and Pertussis (DTaP)

Interventions

Shigella 4V BIOLOGICAL

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

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

MenACWY BIOLOGICAL

Control vaccine administrated to adults and infants

MenACWY-DTaP; MenACWY-Placebo

Rabies BIOLOGICAL

Control vaccine administrated to children

Rabies

Diphtheria, Tetanus and Pertussis (DTaP) BIOLOGICAL

Control vaccine administrated to infants

MenACWY-DTaP

Placebo BIOLOGICAL

Control administrated to adults

MenACWY-Placebo

Eligibility Criteria

• Age: 8 Months - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• LimmaTech Biologics AG: lead
• Kenya Medical Research Institute: collaborator
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator

Study Sites (2)

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

Kericho, 1357-20200, Kenya

Location

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

Kilifi, 230-80108, Kenya

Location

Related Publications (12)

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• Kotloff 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.

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MeSH Terms

Conditions

Dysentery, Bacillary

Interventions

MenACWY; Tetanus Toxoid

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Mainga Hamaluba, MD

  KEMRI/Welcome Trust Research Programme,Kilifi, Kenya

  PRINCIPAL INVESTIGATOR

• Josphat Kosgei, MD

  Medical Research Institute, Kericho, Kenya

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: August 14, 2019
• Study Start: September 2, 2019
• Primary Completion: September 1, 2022
• Study Completion: November 14, 2022
• Last Updated: July 30, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

KE (2)