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

Primary Purpose

Typhoid

Status
Completed
Phase
Phase 2
Locations
Philippines
Study Type
Interventional
Intervention
Vi-DT
FluQuadri™
0.9% sodium chloride isotonic solution
Sponsored by
International Vaccine Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Typhoid focused on measuring Typhoid, Vi-DT, Conjugate vaccine, First in human, New vaccine

Eligibility Criteria

6 Months - 23 Months (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Research Institute for Tropical Medicine(RITM)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

A (Single dose)

B (Two dose)

C (Placebo/Comparator)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
February 12, 2018
Last Updated
August 26, 2021
Sponsor
International Vaccine Institute
Collaborators
SK Bioscience Co., Ltd., Bill and Melinda Gates Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT03527355
Brief Title
Safety, Reactogenicity and Immunogenicity of Vi-DT;Typhoid Conjugate Vaccine
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
April 18, 2018 (Actual)
Primary Completion Date
July 28, 2018 (Actual)
Study Completion Date
January 19, 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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Typhoid
Keywords
Typhoid, Vi-DT, Conjugate vaccine, First in human, New vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants age 6-23 months
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Observer Blinded
Allocation
Randomized
Enrollment
285 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A (Single dose)
Arm Type
Experimental
Arm Description
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.
Arm Title
B (Two dose)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
C (Placebo/Comparator)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Vi-DT
Other Intervention Name(s)
Vi-DT typhoid conjugate vaccine
Intervention Description
Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial
Intervention Type
Biological
Intervention Name(s)
FluQuadri™
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
0.9% sodium chloride isotonic solution
Intervention Description
Manufacture: Euro-Med Inc. Dose: 0.5 mL
Primary Outcome Measure Information:
Title
Safety endpoints: solicited and unsolicited adverse events and serious adverse events
Description
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
Time Frame
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 Measure Information:
Title
Immunogenicity Endpoints
Description
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.
Time Frame
At week 28, 4 weeks after the second vaccination
Other Pre-specified Outcome Measures:
Title
Exploratory Endpoints
Description
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.
Time Frame
At week 4, 4 week after MMR vaccination
Title
Exploratory Endpoints
Description
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.
Time Frame
At week 28, 4 weeks after the second vaccination and at week 96 after the booster dose in selected group.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
23 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria Rosario Capeding, MD
Organizational Affiliation
Research Institute for Tropical Medicine, Metro Manila, Philippines
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Institute for Tropical Medicine(RITM)
City
Alabang
State/Province
Muntinlupa City
ZIP/Postal Code
1781
Country
Philippines

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33150320
Citation
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.
Results Reference
derived
PubMed Identifier
31585725
Citation
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.
Results Reference
derived
Links:
URL
https://doi.org/10.1016/j.vaccine.2019.09.074
Description
A preliminary report

Learn more about this trial

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

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