Immune Non-inferiority and Safety of a Vi-DT Typhoid Conjugate Vaccine

NCT03933098 | Unknown Phase 3 DMC

• 1 other identifier: IVI T003
• Study Type: interventional
• Target: 1,800
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Multicenter, observer-blinded, randomized, Active controlled, Phase 3 study in healthy 6 months to 45 years aged Nepalese at the time of the first vaccine dose. The study objectives are: I. Demonstrate non-inferiority of Vi-DT compared to Typbar TCV® as measured by seroconversion rates of anti-Vi IgG ELISA antibody titers, 4 weeks after single dose (pooled immunogenicity of three lots of Vi-DT) II. Demonstrate the equivalence of immunogenicity as measured by anti-Vi IgG GMT of three lots of Vi-DT vaccine 4 weeks after single dose.

Conditions

Typhoid

Keywords

Typhoid conjugate vaccine; Vi-DT; Safety; Immunogenicity

Outcome Measures

Primary Outcomes (2)

• Seroconversion rate1

  Defined as a 4-fold increase of serum anti-Vi IgG antibody titer

  4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0)

• Geometric Mean Titers (GMT)1

  Measurement of the Geometric Mean Titers (GMT) following 4 weeks after vaccination of three lots of Vi-DT

  4 weeks after vaccination of Vi-DT

Secondary Outcomes (6)

• Geometric Mean Titers (GMT) 2

  4 weeks and 24 weeks after vaccination of Vi-DT(pooled)/ Typbar TCV®

• Seroconversion rate 2

  24 weeks (168 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0).

• Seroconversion rate 3

  4 weeks (28 days) after vaccination of Vi-DT(pooled)

• Seroconversion rate 4

  4 weeks (28 days) after vaccination of Vi-DT(pooled)

• Seroconversion rate 5

  4 weeks (28 days) after vaccination of MR compared to baseline (D0)

Study Arms (4)

Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine)

EXPERIMENTAL

One dose of Vi-DT (typhoid conjugate vaccine) Lot 1 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months.

Biological: Test Vaccine Vi-DT Typhoid conjugate

Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine)

EXPERIMENTAL

One dose of Vi-DT (typhoid conjugate vaccine) Lot 2 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months.

Biological: Test Vaccine Vi-DT Typhoid conjugate

Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine)

EXPERIMENTAL

One dose of Vi-DT (typhoid conjugate vaccine) Lot 3 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months.

Biological: Test Vaccine Vi-DT Typhoid conjugate

Test group D: Typbar TCV

ACTIVE COMPARATOR

One dose of Typbar TCV will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months.

Biological: Control Vaccine Typbar TCV®

Interventions

Test Vaccine Vi-DT Typhoid conjugate BIOLOGICAL

* Manufacturer: SK Bioscience Co., Ltd. * Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid * Dose: 25 µg of Vi polysaccharide/0.5 mL, presented in 3 mL multi-dose glass vial

Also known as: Vi-DT Typhoid conjugate vaccine

Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine); Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine); Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine)

Control Vaccine Typbar TCV® BIOLOGICAL

* Manufacturer: Bharat Biotech * Ingredient: Purified Vi capsular polysaccharide of Salmonella Ty2 conjugated to tetanus toxoid protein * Dose: 0.5 ml

Also known as: Typbar TCV®

Test group D: Typbar TCV

Eligibility Criteria

• Age: 6 Months - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy participants 6 months to 45 years of age at enrollment
• Participants/Parents/LAR who have voluntarily given informed consent/assent
• Participants/Parents/LAR willing to follow the study procedures of the study and available for the entire duration of the study

You may not qualify if:

• Child with a congenital abnormality
• Subject concomitantly enrolled or scheduled to be enrolled in another trial
• Known history of immune function disorders including immunodeficiency diseases (Known HIV infection or other immune function disorders)
• Chronic use of systemic steroids (\>2 mg/kg/day or \>20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic or other immunosuppressive drugs
• Receipt of blood or blood-derived products in the past 3 months
• Subject with a previously ascertained or suspected disease caused by S. Typhi
• Subject who have had household contact with/and or intimate exposure to an individual with laboratory-confirmed S. Typhi
• Individual who has previously received a typhoid vaccine
• Subject who has received or is expected to receive other vaccines from 1 month prior to IP vaccination to Visit 4 (approx.1 month post IP) except PVC booster as per EPI schedule
• Known history or allergy to vaccines or other medications
• History of uncontrolled coagulopathy or blood disorders
• Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the subject and interfere with the assessment of the study objectives
• Any female participant who is lactating, pregnant\* or planning for pregnancy during the course of study period
• Participants/Parents/LAR planning to move from the study area before the end of study period
• Temporary Contraindication

Sponsors & Collaborators

• International Vaccine Institute: lead
• SK Bioscience Co., Ltd.: collaborator

Study Sites (4)

Nepalgunj medical college

Bānke, City- Nepalgunj, Nepal

Location

B.P.Koirala Institute of Health Sciences

Rautahat, Dharan, Nepal

Location

Dhulikhel Hospital

Kavre, Dhulikhel, Nepal

Location

Kanti Children's Hospital

Kathmandu, Sukedhara, 44600, Nepal

Location

Related Publications (1)

• Kumar Rai G, Saluja T, Chaudhary S, Tamrakar D, Kanodia P, Giri BR, Shrestha R, Uranw S, Kim DR, Yang JS, Park IY, Kyung SE, Vemula S, Reddy E J, Kim B, Gupta BP, Jo SK, Ryu JH, Park HK, Shin JH, Lee Y, Kim H, Kim JH, Mojares ZR, Wartel TA, Sahastrabuddhe S. Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial. Lancet Infect Dis. 2022 Apr;22(4):529-540. doi: 10.1016/S1473-3099(21)00455-2. Epub 2021 Dec 20.

  PMID: 34942090 DERIVED

MeSH Terms

Conditions

Typhoid Fever

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Ganesh Kumar Rai, MD

  Kanti Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is observer blind: 1. Vaccine administrator and vaccine safety evaluator at site will be two distinct persons. 2. Laboratory personnel who analyzes immunogenicity at sponsor is also blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants age 6 months to 45 years

Study Record Dates

• First Submitted: April 26, 2019
• First Posted: May 1, 2019
• Study Start: November 15, 2019
• Primary Completion: September 1, 2020
• Study Completion: January 1, 2021
• Last Updated: April 22, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

NE (4)