Safety and Immunogenicity of a Vi-DT Typhoid Conjugate Vaccine

Study Overview
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Brief Summary
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This is a Phase I, Randomized, observer-blinded, age de-escalating study. The study objectives are: To evaluate the safety of 25 μg of Vi-DT typhoid conjugate vaccine administered at 0 and 4 weeks. To assess the immunogenicity of 25 μg of Vi-DT typhoid conjugate vaccine administered at 0 and 4 weeks. To compare the safety and immunogenicity of Vi-DT and Vi-Polysaccharide typhoid vaccines.

Detailed Description
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This study will be carried out in healthy adults and children at a single site. Subjects will be stratified according to age. The study procedure is as follows: Visit 1 (day-1 to -7): Screen participants by medical history, physical examination and lab investigations. Collect blood for safety and immunogenicity assessments. Visit 2 (day 0): Enroll, randomize and administer first dose of vaccine to eligible participants Visit 3 (day 3): Assess participant safety by medical history and physical examination Visit 4 (day 7): Record solicited adverse reaction 7 days post vaccination, and collect blood for safety lab assessments. Visit 5 (day 28): Assess participant safety, collect blood for immunogenicity assessments, and administer second vaccine dose Visit 6 (day 31): Participants safety will be assessed by medical history and physical examination Visit 7 (day 35): Record solicited adverse reaction 7 days post second vaccination. Visit 8 (day 56): Collect blood for immunogenicity assessments, assess participant safety, and fill in study completion form in the absence of any safety concern. This study is observer-blind: vaccine administrator and vaccine safety evaluator will be two distinct persons to avoid bias of safety assessment. Trial staff other than the vaccine administrator.

Official Title
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A Randomized, Observer-Blinded, Phase I Study to Assess the Safety and Immunogenicity of Vi-DT Conjugate Vaccine Compared to Vi-Polysaccharide (Typhim Vi®, Sanofi Pasteur) Typhoid Vaccine in Healthy Filipino Adults and Children

Conditions
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Typhoid

Intervention / Treatment
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* Biological: Vi-DT
* Biological: Typhim Vi®
* Biological: VAXIGRIP®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female individual 2-45 years of age Participants/Parents who have voluntarily given informed consent and/or assent. Participants/Parents willing to commit complying with the study procedures of the investigator and available for the entire duration of study Exclusion Criteria: Participants concomitantly enrolled or scheduled to be enrolled in another trial Acute illness, in particular infectious diseases or fever (axillary temperature > 38°C), with in three days prior to enrollment and vaccination. Known history of allergy to vaccines or other medications Known history of allergy to egg, chiken protein, neomycin and formaldehyde. History of uncontrolled coagulopathy or blood disorders 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 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 trial objectives Pregnancy & Lactation (female adults) Female with child-bearing potential during the study period. i.e., sexually active and not practicing effective acceptable contraceptive method Individuals who have previously received any vaccines against typhoid fever Individuals already immunized with any licensed vaccine within 4 weeks prior to enrolment/vaccination (day 0) and expected to receive other licensed vaccines within 60 days following the first dose (day 0), except for tetanus toxoid vaccine Individuals who have a previously ascertained or suspected disease caused by S. typhi. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory-confirmed S. typhi History of alcohol or substance abuse Subject planning to move from the study area before the end of study period

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 45 Years

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>Two doses of Vi-DT (typhoid conjugate vaccine) will be administrated intramuscularly 4 weeks apart (Day 0 and Day 28). | Biological: Vi-DT<br>* Manufacturer: SK Chemicals Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial<br>* Other names: Vi-DT typhoid conjugate vaccine;|
| Active Comparator: Comparator group<br>Biological/Vaccine: One dose of Typhim Vi® will be administrated intramuscularly at 1st dose (Day 0). One dose of VAXIGRIP® will be administrated intramuscularly at 2nd dose (Day 28). | Biological: Typhim Vi®<br>* Manufacturer: Sanofi Pasteur Ingredient: Purified Vi-polysaccharide Appearance: colourless liquid Dose: 0.5mL/vial<br>Biological: VAXIGRIP®<br>* Dose: Single injection, participants 6-35 months of age will receive 0.25 ml (half a dose), participants 36 months of age and older will receive 0.5ml (full dose) *Participants less than 9 years of age, who have not been vaccinated for flu before, will receive a second dose of flu-vaccine after the last follow-up visit of last participant in their age cohort.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoints for solicited adverse events (reactogenicity) and serious adverse events | Proportion of participants with local and systemic solicited adverse events (reactogenicity) and Proportion of participant with Serious Adverse Events (SAEs) | 4 weeks post first and second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with sero-conversion | Defined as a four-fold rise in anti-Vi antibody titers compared to baseline measured by anti-Vi IgG ELISA and Serum Bactericidal Assay | 4 weeks post first and second injections of Vi-DT and one injection of Vipolysaccharide | 
| Geometric Mean Titers (GMT) | Measurement of the Geometric Mean Titers (GMT) following 4 weeks post first and second injections of Vi-DT and one injection of Vi-polysaccharide vaccine | 4 weeks post first and second vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Typhoid conjugate vaccine, Vi-DT, Safety, Immunogenicuty