Clinical trial NCT04204096: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Typhoid
Keywords: Typhoid conjugate vaccine
Vi-DT
Safety
Immunogenicity
Lead sponsor: International Vaccine Institute
Sponsor class: OTHER
Collaborators: name: SK Bioscience Co., Ltd.
name: Bill and Melinda Gates Foundation
First posted: 2019-12-18
Enrollment: 1800
Sex: ALL
Minimum age (years): 6
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants age 6 months to 45 years
Primary purpose: PREVENTION

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

Eligibility criteria: Inclusion Criteria:

1. Healthy participants 6 months to 45 years of age at enrollment
2. Participants/Parent(s)/LAR who have voluntarily given informed consent/assent
3. Participants/Parent(s)/LAR willing to follow the study procedures of the study and available for the entire duration of the study

Exclusion Criteria:

1. Child with a congenital abnormality
2. Participant who has already received meningococcal conjugate vaccine
3. Participants concomitantly enrolled or scheduled to be enrolled in another trial
4. Known history of immune function disorders including immunodeficiency diseases (Known HIV infection or other immune function disorders)
5. 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
6. Receipt of blood or blood-derived products in the past 3 months
7. Participant with a previously ascertained or suspected disease caused by S. Typhi (confirmed either clinically, serologically or microbiologically)
8. Participant who has had household contact with and/or intimate exposure to an individual with laboratory-confirmed S. Typhi
9. Individual who has previously received a typhoid vaccine
10. 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)
11. Known history or allergy to vaccines or other medications
12. History of uncontrolled coagulopathy or blood disorders
13. 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
14. Any female participant who is lactating, pregnant\* or planning for pregnancy during the course of study period
15. Participants/Parent(s)/LAR planning to move from the study area before the end of study period
16. As per Investigator's medical judgement individual could be excluded from the study in spite of meeting all inclusion/exclusion criteria mentioned above

Primary outcomes:
measure: Geometric Mean Titers (GMT) of anti-Vi IgG
timeFrame: At 4 weeks (28 days) post vaccination of Vi-DT (MD/SD)
Secondary outcomes:
measure: Seroconversion rates of anti-Vi IgG ELISA antibody titres
timeFrame: At 4 weeks (28 days) from baseline (Day 0; before vaccination of Vi-DT (MD/SD)
Other outcomes:
measure: Safety endpoints by each formulation and overall and within each age stratum
timeFrame: Solicited AEs during the 7 days after vaccination/Unsolicited AEs during 4 weeks (28 days) after vaccination/SAEs during the entire study period
Locations:
city: Calamba
country: Philippines
facility: Lingga Health Research Center
state: Laguna
city: San Pablo City
country: Philippines
facility: Magcase Health Center
state: Laguna
city: Muntinlupa
country: Philippines
facility: Putatan Research Center
state: Metro Manila
city: Manila
country: Philippines
facility: University of the Philippines Manila-National Institutes of Health
Study officials:
affiliation: University of the East-Ramon Magsaysay Memorial Medical Center Inc.
name: Josefina C Carlos, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.