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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

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

NCT ID

NCT03527355

First Posted

February 12, 2018

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

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

Studies a U.S. FDA-regulated Device Product

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

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

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

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

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

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

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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