Immune Non-inferiority and Safety of a Vi-DT Typhoid Conjugate Vaccine

Study Overview
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Brief Summary
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This is a Multicenter, observer-blinded, randomized, Active controlled, Phase 3 study in healthy 6 months to 45 years aged Nepalese at the time of the first vaccine dose. The study objectives are: I. Demonstrate non-inferiority of Vi-DT compared to Typbar TCV® as measured by seroconversion rates of anti-Vi IgG ELISA antibody titers, 4 weeks after single dose (pooled immunogenicity of three lots of Vi-DT) II. Demonstrate the equivalence of immunogenicity as measured by anti-Vi IgG GMT of three lots of Vi-DT vaccine 4 weeks after single dose.

Detailed Description
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Subjects will be stratified according to age. The study procedure is as follows: Visit 1 (day-1 to -7): Screen participants by medical/medications history, physical examination, Vital signs, Urine pregnancy test (UPT) Visit 2 (day 0): Enroll, randomize and administer vaccine to eligible participants and assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments. Visit 3 (day 7): Check solicited adverse reaction 7 days post vaccination and Assess participant safety by physical examination and Vital signs Visit 4 (day 28): Assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments Visit 5 (day 84): Assess participant safety by physical examination and Vital signs Visit 6 (day 168): Assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments, 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. For retention: After vaccination, field health worker/designee will contact participant every day till Day 7 by physical visit or by phone call. Follow-up reminder calls will be done very frequently as per discretion of study staff until 24 weeks for all participant to assess participant safety.

Official Title
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A Phase III Multicenter, Observer-Blinded, Randomized, Active Controlled, Immune Non-inferiority and Safety Study of Vi-DT Vaccine Compared to Typbar TCV® in Healthy 6 Months-45 Years Aged Nepalese Participants.

Conditions
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Typhoid

Intervention / Treatment
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* Biological: Test Vaccine Vi-DT Typhoid conjugate
* Biological: Control Vaccine Typbar TCV®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants 6 months to 45 years of age at enrollment Participants/Parents/LAR who have voluntarily given informed consent/assent Participants/Parents/LAR 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 concomitantly enrolled or scheduled to be enrolled in another trial Known history of immune function disorders including immunodeficiency diseases (Known HIV infection or other immune function disorders) Chronic use of systemic steroids (>2 mg/kg/day or >20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic or other immunosuppressive drugs Receipt of blood or blood-derived products in the past 3 months Subject with a previously ascertained or suspected disease caused by S. Typhi Subject who have had household contact with/and or intimate exposure to an individual with laboratory-confirmed S. Typhi Individual who has previously received a typhoid vaccine Subject who has received or is expected to receive other vaccines from 1 month prior to IP vaccination to Visit 4 (approx.1 month post IP) except PVC booster as per EPI schedule Known history or allergy to vaccines or other medications History of uncontrolled coagulopathy or blood 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 Any female participant who is lactating, pregnant* or planning for pregnancy during the course of study period Participants/Parents/LAR planning to move from the study area before the end of study period As per Investigator's medical judgement individuals could be excluded from the study inspite of meeting all inclusion/exclusion criteria mentioned above Temporary Contraindication Acute illness, in particular infectious disease or fever (axillary temperature ≥37.5°C), within three days prior to enrolment and vaccination. Urine pregnancy test (UPT) will be performed in all married females prior to injection

Ages Eligible for Study
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Minimum Age: 6 Months
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
Interventional Model Description: Participants age 6 months to 45 years
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine)<br>One dose of Vi-DT (typhoid conjugate vaccine) Lot 1 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. | Biological: Test Vaccine Vi-DT Typhoid conjugate<br>* Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 25 µg of Vi polysaccharide/0.5 mL, presented in 3 mL multi-dose glass vial<br>* Other names: Vi-DT Typhoid conjugate vaccine;|
| Experimental: Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine)<br>One dose of Vi-DT (typhoid conjugate vaccine) Lot 2 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. | Biological: Test Vaccine Vi-DT Typhoid conjugate<br>* Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 25 µg of Vi polysaccharide/0.5 mL, presented in 3 mL multi-dose glass vial<br>* Other names: Vi-DT Typhoid conjugate vaccine;|
| Experimental: Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine)<br>One dose of Vi-DT (typhoid conjugate vaccine) Lot 3 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. | Biological: Test Vaccine Vi-DT Typhoid conjugate<br>* Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 25 µg of Vi polysaccharide/0.5 mL, presented in 3 mL multi-dose glass vial<br>* Other names: Vi-DT Typhoid conjugate vaccine;|
| Active Comparator: Test group D: Typbar TCV<br>One dose of Typbar TCV will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. | Biological: Control Vaccine Typbar TCV®<br>* Manufacturer: Bharat Biotech Ingredient: Purified Vi capsular polysaccharide of Salmonella Ty2 conjugated to tetanus toxoid protein Dose: 0.5 ml<br>* Other names: Typbar TCV®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate1 | Defined as a 4-fold increase of serum anti-Vi IgG antibody titer | 4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0) | 
| Geometric Mean Titers (GMT)1 | Measurement of the Geometric Mean Titers (GMT) following 4 weeks after vaccination of three lots of Vi-DT | 4 weeks after vaccination of Vi-DT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMT) 2 | Measurement of the Geometric Mean Titers (GMT) following 4 weeks (28 days) and 24 weeks(168 days) after vaccination of Vi-DT (pooled)/ Typbar TCV® | 4 weeks and 24 weeks after vaccination of Vi-DT(pooled)/ Typbar TCV® | 
| Seroconversion rate 2 | Defined as a 4-fold increase of serum anti-Vi IgG antibody titer | 24 weeks (168 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0). | 
| Seroconversion rate 3 | Definded as a Seroconversion rates of anti-Vi IgG ELISA antibody titers after vaccination of three lots of Vi-DT. | 4 weeks (28 days) after vaccination of Vi-DT(pooled) | 
| Seroconversion rate 4 | Definded as a Seroconversion rates of anti-Vi IgG ELISA antibody titers at 4 weeks (28 days) after vaccination of three lots of Vi-DT in each age strata | 4 weeks (28 days) after vaccination of Vi-DT(pooled) | 
| Seroconversion rate 5 | Definded as IgG ELISA antibody titers for Measles (M), and Rubella (R) following single dose of MR a vaccine at baseline D0 and 4 weeks | 4 weeks (28 days) after vaccination of MR compared to baseline (D0) | 
| Safety endpoints for solicited adverse events (reactogenicity) | Proportion of participants with local and systemic solicited adverse events | 7days after vaccination of Vi-DT(pooled)/ Typbar TCV® | 

 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, Immunogenicity