Safety, Reactogenicity and Immunogenicity of Vi-DT;Typhoid Conjugate Vaccine

A Phase II, Randomized, Dose-scheduling, Observer-Blinded Study to Assess the Safety, Reactogenicity and Immunogenicity of Vi-DT Conjugate Vaccine in 6-23-Month Old Healthy Filipino Infants and Toddlers

This is a randomized, observer-blinded Phase 2 study in healthy infants and toddlers 6-23 months of age at the time of the first vaccine dose.

The purpose of this study is to assess the safety and immunogenicity of the Vi-DT vaccine in age group 6-23months of age.

The Vi-DT vaccine is administered at 25 µg either as a single dose, or two doses given 6 months apart.

Study Overview

• Status: Completed
• Conditions: Typhoid
• Intervention / Treatment: Biological: Vi-DT; Biological: FluQuadri™; Other: 0.9% sodium chloride isotonic solution

Detailed Description

This study is carried out in healthy children aged 6 to 23 months at a single site. A total of 285 participants are enrolled, 114, 114 and 57 participants are randomized to either the single dose, two-dose Vi-DT regimens or placebo/comparator group, respectively within age strata. Three age strata is 6 to less than 9 months, 9 to 12 months and 13 to 23 months. The investigators allow the 9-12 months old children to receive Measles-Mumps-Rubella (MMR) vaccine concomitantly with Vi-DT vaccine and descriptive analysis of immune response to MMR only and to MMR and Vi-DT vaccines are performed to assess the possible immunological interference with MMR vaccine.

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 2

Contacts and Locations

Study Locations

• Philippines
  • Muntinlupa City
    • Alabang, Muntinlupa City, Philippines, 1781
      • Research Institute for Tropical Medicine(RITM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy infants and children 6-23 months of age at enrollment as determined by medical history, physical examination and clinical judgment of the investigator
• Birth weight ≥ 2500 g
• ≥ 37 weeks of pregnancy or judge to be full-term by the midwife or birth attendant
• Parents aged 18 years and above and legal guardians aged 21 years and above as per the legal authorization in the Philippines, who have voluntarily given informed consent
• Parents/ legal guardians 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
• Subject with abnormal routine biological values at screening
• Subject concomitantly enrolled or scheduled to be enrolled in another trial
• Acute illness, in particular infectious disease or fever (axillary temperature ≥37.5°C), within three days prior to enrolment and vaccination
• Known history of immune function disorders including immunodeficiency diseases, or chronic use of systemic steroids (>20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic or other immunosuppressive drugs
• Child with a previously ascertained or suspected disease caused by S. typhi
• Child who have had household contact with/and or intimate exposure to an individual with laboratory-confirmed S. typhi
• Known history or allergy to vaccines or other medications
• Know history of allergy to eggs, chicken protein, neomycin and formaldehyde
• History of uncontrolled coagulopathy or blood disorders
• Mother has known HIV infection or other immune function 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
• Child whose parents or legal guardian planning to move from the study area before the end of study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A (Single dose); One dose of Vi-DT (Typhoid conjugate vaccine) 25 µg 0.5 mL is administrated intramuscularly at first dost (Day 0). One dose of FluQuadri™ 0.25mL is administrated intramuscularly at second dose (Week 24). One booster dose of Vi-DT 0.5 mL is administrated 2 years apart (Week 96). MMR for age group at 9-12 months.	Biological: Vi-DT; Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial; Other Names: Vi-DT typhoid conjugate vaccine; Biological: FluQuadri™; Manufacturer: Sanofi Pasteur Dose: 0.25 ml *Participants who have not been vaccinated for flu before, will receive a second dose of flu-vaccine after unblinding.
Active Comparator: B (Two dose); Two doses of Vi-DT (Typhoid conjugate vaccine) 25 µg 0.5 mL is administrated intramuscularly 6 months apart (Day 0 and Day 168 (Week 24)). MMR for age group at 9-12 months.	Biological: Vi-DT; Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial; Other Names: Vi-DT typhoid conjugate vaccine
Placebo Comparator: C (Placebo/Comparator); One dose of Placebo (0.9% sodium chloride isotonic solution) 0.5 mL is administrated intramuscularly at first dost (Day 0). One dose of FluQuadri™ 0.25mL is administrated intramuscularly at second dose (Day 168; Week 24). MMR for age group at 9-12 months.	Biological: FluQuadri™; Manufacturer: Sanofi Pasteur Dose: 0.25 ml *Participants who have not been vaccinated for flu before, will receive a second dose of flu-vaccine after unblinding.; Other: 0.9% sodium chloride isotonic solution; Manufacture: Euro-Med Inc. Dose: 0.5 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints: solicited and unsolicited adverse events and serious adverse events	Frequency (percentage) of solicited local reactions at the injection site: Pain, tenderness, erythema/redness, swelling/induration and pruritus local; Frequency (percentage) of solicited systemic reactions: Fever, lethargy, irritability, vomiting, diarrhea, drowsiness, loss of appetite, persistent crying, rash and nasopharyngitis; Frequency (percentage) of unsolicited adverse events; Frequency (percentage) of serious adverse events	Solicited AE: during 7 days after each vaccination. Unsolicited AE: after the first vaccination until 4 weeks after the second vaccination. SAE will be captured after the first vaccination up to week 100 for Group A, week 96 for Group B, week 36 Group C

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Endpoints	Seroconversion rate of anti-Vi IgG by Geometric Mean Titers (GMT) will be measured 4 weeks after the second vaccination using an in-house ELISA assay using standardized reagents and reference serum. The level of the specific anti-Vi IgG in ELISA units for each serum sample is determined by comparison to a reference serum. The number of anti-Vi IgG positive sera will be used to calculate the seroconversion rates.	At week 28, 4 weeks after the second vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoints	Seroconversion rates of Measles, Mumps and Rubella will be determined 4 week after MMR vaccination. Serum titers will be measured by routinely used commercially available ELISA kits. Kit-specific threshold of positivity will be used to determine specific seroconversion rates.	At week 4, 4 week after MMR vaccination
Exploratory Endpoints	Serum bactericidal titers will be determined using in-house functional assay assessing the number of survived S. Typhi Ty2 strain colony on Luria-Bertani plate. Serum bactericidal titer is defined as the highest dilution of serum that gives 50% of inhibition of colony formation of S. Typhi.	At week 28, 4 weeks after the second vaccination and at week 96 after the booster dose in selected group.

Collaborators and Investigators

• Sponsor: International Vaccine Institute
• Collaborators: Bill and Melinda Gates Foundation; SK Bioscience Co., Ltd.
• Investigators: Principal Investigator: Maria Rosario Capeding, MD, Research Institute for Tropical Medicine, Metro Manila, Philippines

Publications and helpful links

General Publications

• Capeding MR, Sil A, Tadesse BT, Saluja T, Teshome S, Alberto E, Kim DR, Park EL, Park JY, Yang JS, Chinaworapong S, Park J, Jo SK, Chon Y, Yang SY, Ryu JH, Cheong I, Shim KY, Lee Y, Kim H, Lynch JA, Kim JH, Excler JL, Wartel TA, Sahastrabuddhe S. Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study. EClinicalMedicine. 2020 Sep 9;27:100540. doi: 10.1016/j.eclinm.2020.100540. eCollection 2020 Oct.
• Capeding MR, Alberto E, Sil A, Saluja T, Teshome S, Kim DR, Park JY, Yang JS, Chinaworapong S, Park J, Jo SK, Chon Y, Yang SY, Ham DS, Ryu JH, Lynch J, Kim JH, Kim H, Excler JL, Wartel TA, Sahastrabuddhe S. Immunogenicity, safety and reactogenicity of a Phase II trial of Vi-DT typhoid conjugate vaccine in healthy Filipino infants and toddlers: A preliminary report. Vaccine. 2020 Jun 9;38(28):4476-4483. doi: 10.1016/j.vaccine.2019.09.074. Epub 2019 Oct 1.

Helpful Links

• A preliminary report

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2018
• Primary Completion (Actual): July 28, 2018
• Study Completion (Actual): January 19, 2021

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 17, 2018

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 26, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Conjugate vaccine; Typhoid; First in human; Vi-DT; New vaccine
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: IVI T002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No