Immune Equivalence Between Multi-dose and Single Dose Formulation of Vi-DT and Their Overall Safety (Phase III)

NCT04204096 | Completed Phase 3 DMC

• 1 other identifier: IVI T004
• Study Type: interventional
• Target: 1,800
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multicenter, randomized, observer-blinded, controlled, immune equivalence study of a multi-dose (MD) formulation with 2PE preservative of SK bioscience Vi-DT compared to single dose (SD) formulation without preservative of SK bioscience Vi-DT in participant (6 months - 45 years) including safety population. The study objectives are as follows:

• Primary objective. Demonstrate the immune equivalence as measured by anti-Vi IgG Geometric Mean Titer (GMT) of multi dose formulation against single dose formulation of Vi-DT (18-45 year age stratum), at 4 weeks after a single dose.
• Secondary objective 1. Demonstrate the immune equivalence as measured by seroconversion rates of anti-Vi IgG antibody titres of multi dose formulation against single dose formulation of Vi-DT vaccine (18-45 year age stratum) at 4 weeks after a single dose.
• Secondary objective 2. Describe safety profile in all age strata combined (age 6 months - 45 years old) and in each age stratum, at 4 weeks after a single dose of SD/MD formulation/control (Meningococcal Conjugate Vaccine). There are total 5 scheduled visits as follows:
• Visit 1(D-7 to 0): Screening
• Visit 2(D0): Enrollment, vaccination, safety follow-up and blood collection for immunogenicity assessment (only for subjects 18 years old and above)
• Visit 3(D7): Safety follow-up
• Visit 4(D28): Safety follow-up and blood collection for immunogenicity assessment (only for subjects 18 years old and above)
• V5(D168): Safety follow-up

Conditions

Typhoid

Keywords

Typhoid conjugate vaccine; Vi-DT; Safety; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• Geometric Mean Titers (GMT) of anti-Vi IgG

  If the 95% confidence interval of the ratio of GMT estimate of Vi-DT(MD) over GMT of Vi-DT(SD) is located within the bounds of 0.67to 1.5, then Vi-DT (MD) is equivalent to Vi-DT (SD) in terms of GMT of anti-Vi IgG with significance level of 0.05.

  At 4 weeks (28 days) post vaccination of Vi-DT (MD/SD)

Secondary Outcomes (1)

• Seroconversion rates of anti-Vi IgG ELISA antibody titres

  At 4 weeks (28 days) from baseline (Day 0; before vaccination of Vi-DT (MD/SD)

Other Outcomes (1)

• Safety endpoints by each formulation and overall and within each age stratum

  Solicited AEs during the 7 days after vaccination/Unsolicited AEs during 4 weeks (28 days) after vaccination/SAEs during the entire study period

Study Arms (3)

Vi-DT Multi-dose

EXPERIMENTAL

* 750 participants (6 mo - 45 yrs) * Dose: 0.5mL, Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein (Vi-DT), manufactured by SK bioscience (Republic of Korea) * Dosage form: Liquid, 25µg Vi polysaccharide/0.5mL, presented in Type I glass vial (multi-dose formulation Vi-DT contains preservative 2 PE) * Mode of Administration: Intramuscular injection * Frequency of administration: Once

Biological: Vi-DT (Multi-dose formulation)

Vi-DT Single-dose

EXPERIMENTAL

* 750 participants (6 mo - 45 yrs) * Dose: 0.5mL, Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein (Vi-DT), manufactured by SK bioscience (Republic of Korea) * Dosage form: Liquid, 25µg Vi polysaccharide/0.5mL, presented in Type I glass vial (single dose formulation Vi-DT without any preservative) * Mode of Administration: Intramuscular injection * Frequency of administration: Once

Biological: Vi-DT (Single dose formulation)

Control

ACTIVE COMPARATOR

* 300 participants (6 mo - 45 yrs) * Dose: 0.5mL, Locally available Meningococcal conjugate vaccine * Dosage form: Lyophilized white powder * Mode of Administration: Intramuscular injection * Frequency of administration: Once (For participants 6 months to 1 year, one more dose will be provided after the study unblinding)

Biological: Control Vaccine

Interventions

Vi-DT (Multi-dose formulation) BIOLOGICAL

* Manufacturer: SK bioscience Co., Ltd. * Dose formulation: 25 µg Vi polysaccharide /0.5 mL, presented in Type I glass vial (multi dose Vi-DT with preservative 2 PE) * Mode of Administration: 0.5 mL by intramuscular injection in the left anterolateral thigh or left arm deltoid region in participants below 2 years of age, less dominant arm deltoid region in age group 2 to 45 years * Storage Conditions: +2 to +8°C

Also known as: Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein

Vi-DT Multi-dose

Vi-DT (Single dose formulation) BIOLOGICAL

* Manufacturer: SK bioscience Co., Ltd. * Dose formulation: 25 µg Vi polysaccharide /0.5 mL, presented in Type I glass vial (single dose Vi-DT without any preservative) * Mode of Administration: 0.5 mL by intramuscular injection in the left anterolateral thigh or left arm deltoid region in participants below 2 years of age, less dominant arm deltoid region in age group 2-45 years * Storage Conditions: +2 to +8°C

Also known as: Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein

Vi-DT Single-dose

Control Vaccine BIOLOGICAL

* For participant ≥ 1 year one dose of locally licensed Meningococcal conjugate vaccine will be administered * For participants 6 months to 1 year one dose of locally licensed Meningococcal conjugate vaccine will be administered during the study and the next dose will be provided after the study unblinding at the completion of 6 months follow up of last subject.

Also known as: Locally available Meningococcal conjugate vaccine

Control

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/Parent(s)/LAR who have voluntarily given informed consent/assent
• Participants/Parent(s)/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
• Participant who has already received meningococcal conjugate vaccine
• Participants 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
• Participant with a previously ascertained or suspected disease caused by S. Typhi (confirmed either clinically, serologically or microbiologically)
• Participant who has had household contact with and/or intimate exposure to an individual with laboratory-confirmed S. Typhi
• Individual who has previously received a typhoid vaccine
• Participant who has received other vaccines from 1 month prior to test vaccination or planned to receive any vaccine within 1 month (except a measles containing vaccine as per government vaccination campaign)
• 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 participant 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/Parent(s)/LAR planning to move from the study area before the end of study period

Sponsors & Collaborators

• International Vaccine Institute: lead
• SK Bioscience Co., Ltd.: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (4)

Lingga Health Research Center

Calamba, Laguna, 4027, Philippines

Location

Magcase Health Center

San Pablo, Laguna, 4000, Philippines

Location

Putatan Research Center

Muntinlupa, National Capital Region, 1772, Philippines

Location

University of the Philippines Manila-National Institutes of Health

Manila, 1000, Philippines

Location

Related Publications (1)

• Carlos JC, Tadesse BT, Borja-Tabora C, Alberto E, Ylade MC, Sil A, Kim DR, Ahn HS, Yang JS, Lee JY, Kim MS, Park J, Kwon SY, Kim H, Yang SY, Ryu JH, Park H, Shin JH, Lee Y, Kim JH, Mojares ZR, Wartel TA, Sahastrabuddhe S. A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age. Lancet Reg Health West Pac. 2022 May 30;24:100484. doi: 10.1016/j.lanwpc.2022.100484. eCollection 2022 Jul.

  PMID: 35664443 DERIVED

MeSH Terms

Conditions

Typhoid Fever

Interventions

Diphtheria Toxoid; Dosage Forms

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Josefina C Carlos, MD

  University of the East-Ramon Magsaysay Memorial Medical Center Inc.

  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: December 17, 2019
• First Posted: December 18, 2019
• Study Start: February 4, 2020
• Primary Completion: September 11, 2020
• Study Completion: January 29, 2021
• Last Updated: August 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

PH (4)