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

Primary Purpose

Typhoid

Status

Unknown status

Phase

Phase 3

Locations

Nepal

Study Type

Interventional

Intervention

Test Vaccine Vi-DT Typhoid conjugate

Control Vaccine Typbar TCV®

About this trial

This is an interventional prevention trial for Typhoid focused on measuring Typhoid conjugate vaccine, Vi-DT, Safety, Immunogenicity

Eligibility Criteria

6 Months - 45 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Nepalgunj medical college
B.P.Koirala Institute of Health Sciences
Dhulikhel Hospital
Kanti Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine)

Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine)

Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine)

Test group D: Typbar TCV

Arm Description

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.

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.

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.

One dose of Typbar TCV will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months.

Outcomes

Primary Outcome Measures

Seroconversion rate1

Defined as a 4-fold increase of serum anti-Vi IgG antibody titer

Geometric Mean Titers (GMT)1

Measurement of the Geometric Mean Titers (GMT) following 4 weeks after vaccination of three lots of Vi-DT

Secondary Outcome Measures

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®

Seroconversion rate 2

Defined as a 4-fold increase of serum anti-Vi IgG antibody titer

Seroconversion rate 3

Definded as a Seroconversion rates of anti-Vi IgG ELISA antibody titers after vaccination of three lots of Vi-DT.

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

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

Safety endpoints for solicited adverse events (reactogenicity)

Proportion of participants with local and systemic solicited adverse events

Full Information

NCT ID

NCT03933098

First Posted

April 26, 2019

Last Updated

April 21, 2020

Sponsor

International Vaccine Institute

Collaborators

SK Bioscience Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03933098

Brief Title

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

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Unknown status

Study Start Date

November 15, 2019 (Actual)

Primary Completion Date

September 2020 (Anticipated)

Study Completion Date

January 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

International Vaccine Institute

Collaborators

SK Bioscience Co., Ltd.

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 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Typhoid

Keywords

Typhoid conjugate vaccine, Vi-DT, Safety, Immunogenicity

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Participants age 6 months to 45 years

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

This study is observer blind: Vaccine administrator and vaccine safety evaluator at site will be two distinct persons. Laboratory personnel who analyzes immunogenicity at sponsor is also blinded.

Allocation

Randomized

Enrollment

1800 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine)

Arm Type

Experimental

Arm Description

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.

Arm Title

Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine)

Arm Type

Experimental

Arm Description

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.

Arm Title

Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine)

Arm Type

Experimental

Arm Description

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.

Arm Title

Test group D: Typbar TCV

Arm Type

Active Comparator

Arm Description

One dose of Typbar TCV will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months.

Intervention Type

Biological

Intervention Name(s)

Test Vaccine Vi-DT Typhoid conjugate

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: 25 µg of Vi polysaccharide/0.5 mL, presented in 3 mL multi-dose glass vial

Intervention Type

Biological

Intervention Name(s)

Control Vaccine Typbar TCV®

Other Intervention Name(s)

Typbar TCV®

Intervention Description

Manufacturer: Bharat Biotech Ingredient: Purified Vi capsular polysaccharide of Salmonella Ty2 conjugated to tetanus toxoid protein Dose: 0.5 ml

Primary Outcome Measure Information:

Title

Seroconversion rate1

Description

Defined as a 4-fold increase of serum anti-Vi IgG antibody titer

Time Frame

4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0)

Title

Geometric Mean Titers (GMT)1

Description

Measurement of the Geometric Mean Titers (GMT) following 4 weeks after vaccination of three lots of Vi-DT

Time Frame

4 weeks after vaccination of Vi-DT

Secondary Outcome Measure Information:

Title

Geometric Mean Titers (GMT) 2

Description

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®

Time Frame

4 weeks and 24 weeks after vaccination of Vi-DT(pooled)/ Typbar TCV®

Title

Seroconversion rate 2

Description

Defined as a 4-fold increase of serum anti-Vi IgG antibody titer

Time Frame

24 weeks (168 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0).

Title

Seroconversion rate 3

Description

Definded as a Seroconversion rates of anti-Vi IgG ELISA antibody titers after vaccination of three lots of Vi-DT.

Time Frame

4 weeks (28 days) after vaccination of Vi-DT(pooled)

Title

Seroconversion rate 4

Description

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

Time Frame

4 weeks (28 days) after vaccination of Vi-DT(pooled)

Title

Seroconversion rate 5

Description

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

Time Frame

4 weeks (28 days) after vaccination of MR compared to baseline (D0)

Title

Safety endpoints for solicited adverse events (reactogenicity)

Description

Proportion of participants with local and systemic solicited adverse events

Time Frame

7days after vaccination of Vi-DT(pooled)/ Typbar TCV®

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ganesh Kumar Rai, MD

Organizational Affiliation

Kanti Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nepalgunj medical college

City

Banke

State/Province

City- Nepalgunj

Country

Nepal

Facility Name

B.P.Koirala Institute of Health Sciences

City

Rautahat

State/Province

Dharan

Country

Nepal

Facility Name

Dhulikhel Hospital

City

Kavre

State/Province

Dhulikhel

Country

Nepal

Facility Name

Kanti Children's Hospital

City

Kathmandu

State/Province

Sukedhara

ZIP/Postal Code

44600

Country

Nepal

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34942090

Citation

Kumar Rai G, Saluja T, Chaudhary S, Tamrakar D, Kanodia P, Giri BR, Shrestha R, Uranw S, Kim DR, Yang JS, Park IY, Kyung SE, Vemula S, Reddy E J, Kim B, Gupta BP, Jo SK, Ryu JH, Park HK, Shin JH, Lee Y, Kim H, Kim JH, Mojares ZR, Wartel TA, Sahastrabuddhe S. Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial. Lancet Infect Dis. 2022 Apr;22(4):529-540. doi: 10.1016/S1473-3099(21)00455-2. Epub 2021 Dec 20.

Results Reference

derived

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

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