A Study on the Immune Response and Safety of a Multicomponent Shigella Vaccine in Preventing Shigellosis in Infants

NCT06663436 | Completed Phase 2 DMC

• 1 other identifier: 219449
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the immune response and safety of a multicomponent, 2-dose Shigella vaccine in preventing shigellosis in African infants. The candidate vaccine, altSonflex1-2-3, is currently being evaluated in a Phase 2 age de-escalation (from least vulnerable adult population to most vulnerable paediatric population) clinical study in Kenya, with the aim of identifying a preferred dose, using a 3-dose vaccination schedule in infants from 9 months of age (NCT05073003). This Phase 2 clinical study will evaluate the safety and immunogenicity of an alternative 2-dose vaccination schedule.

Conditions

Diarrhoea

Keywords

Shigella; Shigellosis; altSonflex1-2-3; Infants; African; Safety; Immunogenicity

Outcome Measures

Primary Outcomes (11)

• Geometric mean titers (GMTs) of anti-serotype-specific Shigella lipopolysaccharides/O-antigen (LPS/OAg) serum Immunoglobulin G (IgG)

  Day 1 (before administration of Dose 1)

• GMTs of anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 169 (before administration of Dose 2)

• GMTs of anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 29 (28 days after administration of Dose 1)

• GMTs of anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 197 (28 days after administration of Dose 2)

• Geometric mean concentrations (GMCs) of anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 1 (before administration of Dose 1)

• GMCs of anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 169 (before administration of Dose 2)

• GMCs of anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 29 (28 days after administration of Dose 1)

• GMCs of anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 197 (28 days after administration of Dose 2)

• Number of infants with at least a 4-fold increase in anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 29 compared with baseline (Day 1)

• Number of infants with at least a 4-fold increase in anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 197 compared with baseline (Day 1)

• Number of infants with at least a 4-fold increase in anti-serotype-specific Shigella LPS/OAg serum IgG

  Day 197 compared with pre-Dose 2 (Day 169)

Secondary Outcomes (10)

• Number of infants with solicited administration-site events

  During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 169)

• Number of infants with solicited systemic events

  During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 169)

• Number of infants with unsolicited adverse events (AEs)

  During 28 days after each study intervention administration (study interventions administered at Day 1 and Day 169)

• Number of infants with serious adverse events (SAEs) during the entire study period

  From Day 1 to Day 197

• Number of infants with deviations from laboratory reference values of hematological, renal, and hepatic panel test results

  Day 8 compared with baseline (Day 1)

Study Arms (4)

altSonflex1-2-3 Dose_A Group

EXPERIMENTAL

Participants randomized to receive altSonflex1-2-3 Dose A and MR-VAC on Day 1 and Day 169.

Biological: altSonflex1-2-3 Dose A; Biological: MR-VAC

altSonflex1-2-3 Dose_B Group

EXPERIMENTAL

Participants randomized to receive altSonflex1-2-3 Dose B and MR-VAC on Day 1 and Day 169.

Biological: altSonflex1-2-3 Dose B; Biological: MR-VAC

altSonflex1-2-3 Dose_C Group

EXPERIMENTAL

Participants randomized to receive altSonflex1-2-3 Dose C and MR-VAC on Day 1 and Day 169.

Biological: altSonflex1-2-3 Dose C; Biological: MR-VAC

Control Group

ACTIVE COMPARATOR

Participants randomized to receive TYPHIBEV on Day 1, Infanrix hexa on Day 169 and MR-VAC on Day 1 and Day 169.

Biological: TYPHIBEV; Combination Product: Infanrix hexa; Biological: MR-VAC

Interventions

altSonflex1-2-3 Dose A BIOLOGICAL

altSonflex1-2-3 Dose A administered intramuscularly on Day 1 and Day 169

Also known as: Shigella vaccine

altSonflex1-2-3 Dose_A Group

altSonflex1-2-3 Dose B BIOLOGICAL

altSonflex1-2-3 Dose B administered intramuscularly on Day 1 and Day 169

Also known as: Shigella vaccine

altSonflex1-2-3 Dose_B Group

TYPHIBEV BIOLOGICAL

TYPHIBEV administered intramuscularly on Day 1

Also known as: Biological E. Limited's Typhoid Vi-CRM197 conjugate vaccine

Control Group

Infanrix hexa COMBINATION_PRODUCT

Infanrix hexa administered intramuscularly on Day 169

Also known as: GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated) and Haemophilus influenzae type b vaccine (adsorbed)

Control Group

MR-VAC BIOLOGICAL

MR-VAC co-administered subcutaneously on Day 1 and Day 169

Also known as: Serum Institute of India's Measles and rubella vaccine (live)

Control Group; altSonflex1-2-3 Dose_A Group; altSonflex1-2-3 Dose_B Group; altSonflex1-2-3 Dose_C Group

altSonflex1-2-3 Dose C BIOLOGICAL

altSonflex1-2-3 Dose C administered intramuscularly on Day 1 and Day 169

Also known as: Shigella vaccine

altSonflex1-2-3 Dose_C Group

Eligibility Criteria

• Age: 39 Weeks - 43 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Participants' parent(s)/ Legally acceptable representative (LAR), who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written or witnessed/thumb printed informed consent obtained from the 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.
• A male or female 9 months of age at the time of the first study intervention administration.
• Normal nutritional z-score.
• Previously completed routine childhood vaccinations to the best knowledge of the participant's parent(s)/LAR(s).
• Born at a gestation period of \>=37 weeks to the best knowledge of the participant's parent(s)/LAR(s).
• Participants negative for human immunodeficiency virus as confirmed by DNA polymerase chain reaction testing.
• Participants negative for HLA-B27.

You may not qualify if:

• Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant's parent(s)/LAR(s) or documented by participant's records.
• Progressive, unstable, or uncontrolled clinical conditions.
• History (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
• Major congenital defects, as assessed by the investigator.
• Recurrent history or uncontrolled neurological disorders or seizures.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Hypersensitivity (known or suspected), including allergy, to medicinal products, vaccines, or medical equipment whose use is foreseen in this study.
• Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• Any behavioral 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.
• Acute disease and/or fever (defined as temperature \>=38.0°C) at the time of enrollment.
• Any clinically significant hematological and/or biochemical laboratory abnormality.
• Confirmed positive COVID-19 test during the period starting 30 days before the first administration of study interventions (Day -30 to Day 1).
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -30 to Day 1), or their planned use during the study period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Kericho, 20200, Kenya

Location

MeSH Terms

Conditions

Diarrhea; Dysentery, Bacillary

Interventions

Shigella Vaccines; diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine; Tetanus Toxoid; Hepatitis B Vaccines; Rubella Vaccine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; 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)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Toxoids; Viral Hepatitis Vaccines; Viral Vaccines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2024
• First Posted: October 29, 2024
• Study Start: November 13, 2024
• Primary Completion: October 21, 2025
• Study Completion: October 21, 2025
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

KE (1)