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

Primary Purpose

Typhoid

Status

Completed

Phase

Phase 3

Locations

Philippines

Study Type

Interventional

Intervention

Vi-DT (Multi-dose formulation)

Vi-DT (Single dose formulation)

Control Vaccine

About this trial

This is an interventional prevention trial for Typhoid focused on measuring Typhoid conjugate vaccine, Vi-DT, Safety, Immunogenicity

Eligibility Criteria

6 Months - 45 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
As per Investigator's medical judgement individual could be excluded from the study in spite of meeting all inclusion/exclusion criteria mentioned above

Sites / Locations

Lingga Health Research Center
Magcase Health Center
Putatan Research Center
University of the Philippines Manila-National Institutes of Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Vi-DT Multi-dose

Vi-DT Single-dose

Control

Arm Description

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

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

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Seroconversion rates of anti-Vi IgG ELISA antibody titres

If the 95% confidence interval of the estimate of difference of seroconversion rate between Vi-DT (MD) and Vi-DT (SD) at 4 weeks (Day 28) is located within the bounds -10% to 10%, then Vi-DT (MD) is equivalent to Vi-DT (SD) in terms of sero-conversion rate, which is defined as 4 fold increase of anti Vi IgG from baseline with significance level of 0.05.

Full Information

NCT ID

NCT04204096

First Posted

December 17, 2019

Last Updated

August 26, 2021

Sponsor

International Vaccine Institute

Collaborators

SK Bioscience Co., Ltd., Bill and Melinda Gates Foundation

1. Study Identification

Unique Protocol Identification Number

NCT04204096

Brief Title

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

Official Title

A Phase III, Multicenter, Observer Blind, Randomized, Controlled Study to Evaluate Immune Equivalence of Multi-dose Formulation Against Single-dose Formulation of Vi-DT Typhoid Conjugate Vaccine and Safety in Healthy Filipino......

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

February 4, 2020 (Actual)

Primary Completion Date

September 11, 2020 (Actual)

Study Completion Date

January 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

International Vaccine Institute

Collaborators

SK Bioscience Co., Ltd., Bill and Melinda Gates Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

Detailed Description

The vaccines will be administered to 1,500 healthy participants of 6 months to 45 years of age and followed up for 24 weeks after the injection for safety. Adult participants (N=500) will be followed up for immunogenicity at 4 weeks and all participants till 24 weeks for safety post single dose of either MD & SD formulations. 300 healthy participants will be given control vaccine (locally available licensed Meningococcal conjugate vaccine) to check the background safety events. The primary objective is to demonstrate the equivalence of immunogenicity as measured by anti-Vi IgG GMT titer at 4 weeks after a single dose of MD/SD formulation in adults. The secondary objective is to demonstrate the equivalence of immunogenicity in terms of seroconversion rates as measured by anti-Vi IgG ELISA antibody titers, at 4 weeks after a single dose of MD/SD formulation in adults. A descriptive evaluation of safety at 4 and 24 weeks post single dose of (SD/MD/Meningococcal vaccine), will be performed. The Vi-DT vaccine from both MD & SD formulations will be administered as a single dose of 25 µg/0.5 mL. Eligible participants enrolled into the study will be randomized into one of the three study groups within each age stratum of 6 months to less than 2 years, 2 to less than 18 years, and 18 to 45 years. Participants will be observed at the study site for 30 minutes after vaccination for safety assessment. Solicited adverse events will be recorded on a diary card during 7 days after vaccination. Unsolicited adverse events will be recorded during the 4 weeks after vaccination. Serious adverse events will be recorded during the entire study period. With the exception of designated study site personnel responsible for vaccine administration, site investigators, study nurse, and those assessing clinical outcomes, and data analysts will be blinded to vaccine allocation until data base lock for the final analysis. Blood samples will be collected at baseline prior to vaccination and at 4 weeks post vaccination from adults (18-45 years) for immunogenicity assessment

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Typhoid

Keywords

Typhoid conjugate vaccine, Vi-DT, Safety, Immunogenicity

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Participants age 6 months to 45 years

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

This study is observer blind: Vaccine administrator and vaccine safety evaluator at site will be two distinct persons. Laboratory personnel who analyzes immunogenicity at sponsor is also blinded.

Allocation

Randomized

Enrollment

1800 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vi-DT Multi-dose

Arm Type

Experimental

Arm Description

Arm Title

Vi-DT Single-dose

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

Active Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Vi-DT (Multi-dose formulation)

Other Intervention Name(s)

Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Vi-DT (Single dose formulation)

Other Intervention Name(s)

Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Control Vaccine

Other Intervention Name(s)

Locally available Meningococcal conjugate vaccine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Geometric Mean Titers (GMT) of anti-Vi IgG

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Seroconversion rates of anti-Vi IgG ELISA antibody titres

Description

Time Frame

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

Other Pre-specified Outcome Measures:

Title

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

Description

Frequency of local and systemic solicited adverse events during the 7 days after each dose Solicited local reactions at the site of injection: pain, tenderness, erythema/redness, swelling/induration and pruritus Solicited systemic reactions (adapted to each age group): fever, lethargy, irritability, nausea/vomiting, arthralgia, diarrhea, drowsiness, loss of appetite, chills, headache, fatigue, myalgia and persistent crying Frequency of unsolicited adverse events during 4 weeks (28 days) after vaccination Frequency of Serious Adverse Events during the entire study period

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 As per Investigator's medical judgement individual could be excluded from the study in spite of meeting all inclusion/exclusion criteria mentioned above

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Josefina C Carlos, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lingga Health Research Center

City

Calamba

State/Province

Laguna

ZIP/Postal Code

4027

Country

Philippines

Facility Name

Magcase Health Center

City

San Pablo City

State/Province

Laguna

ZIP/Postal Code

4000

Country

Philippines

Facility Name

Putatan Research Center

City

Muntinlupa

State/Province

Metro Manila

ZIP/Postal Code

1772

Country

Philippines

Facility Name

University of the Philippines Manila-National Institutes of Health

City

Manila

ZIP/Postal Code

1000

Country

Philippines

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35664443

Citation

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.

Results Reference

derived

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

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