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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Typhoid

Intervention / Treatment
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* Biological: Vi-DT
* Biological: FluQuadri™
* Other: 0.9% sodium chloride isotonic solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants age 6-23 months
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (Single dose)<br>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<br>* Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial<br>* Other names: Vi-DT typhoid conjugate vaccine;Biological: FluQuadri™<br>* 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.<br>|
| Active Comparator: B (Two dose)<br>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<br>* Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial<br>* Other names: Vi-DT typhoid conjugate vaccine;|
| Placebo Comparator: C (Placebo/Comparator)<br>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™<br>* 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.<br>Other: 0.9% sodium chloride isotonic solution<br>* Manufacture: Euro-Med Inc. Dose: 0.5 mL<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Typhoid, Vi-DT, Conjugate vaccine, First in human, New vaccine