Clinical trial NCT03933098: 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Typhoid
Keywords: Typhoid conjugate vaccine
Vi-DT
Safety
Immunogenicity
Lead sponsor: International Vaccine Institute
Sponsor class: OTHER
Collaborators: name: SK Bioscience Co., Ltd.
First posted: 2019-05-01
Enrollment: 1800
Sex: ALL
Minimum age (years): 6
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants age 6 months to 45 years
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Healthy participants 6 months to 45 years of age at enrollment
2. Participants/Parents/LAR who have voluntarily given informed consent/assent
3. Participants/Parents/LAR willing to follow the study procedures of the study and available for the entire duration of the study

Exclusion Criteria:

1. Child with a congenital abnormality
2. Subject concomitantly enrolled or scheduled to be enrolled in another trial
3. Known history of immune function disorders including immunodeficiency diseases (Known HIV infection or other immune function disorders)
4. 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
5. Receipt of blood or blood-derived products in the past 3 months
6. Subject with a previously ascertained or suspected disease caused by S. Typhi
7. Subject who have had household contact with/and or intimate exposure to an individual with laboratory-confirmed S. Typhi
8. Individual who has previously received a typhoid vaccine
9. 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
10. Known history or allergy to vaccines or other medications
11. History of uncontrolled coagulopathy or blood disorders
12. 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
13. Any female participant who is lactating, pregnant\* or planning for pregnancy during the course of study period
14. Participants/Parents/LAR planning to move from the study area before the end of study period
15. As per Investigator's medical judgement individuals could be excluded from the study inspite of meeting all inclusion/exclusion criteria mentioned above

    Temporary Contraindication
16. 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

Primary outcomes:
measure: Seroconversion rate1
timeFrame: 4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0)
measure: Geometric Mean Titers (GMT)1
timeFrame: 4 weeks after vaccination of Vi-DT
Secondary outcomes:
measure: Geometric Mean Titers (GMT) 2
timeFrame: 4 weeks and 24 weeks after vaccination of Vi-DT(pooled)/ Typbar TCV®
measure: Seroconversion rate 2
timeFrame: 24 weeks (168 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0).
measure: Seroconversion rate 3
timeFrame: 4 weeks (28 days) after vaccination of Vi-DT(pooled)
measure: Seroconversion rate 4
timeFrame: 4 weeks (28 days) after vaccination of Vi-DT(pooled)
measure: Seroconversion rate 5
timeFrame: 4 weeks (28 days) after vaccination of MR compared to baseline (D0)
measure: Safety endpoints for solicited adverse events (reactogenicity)
timeFrame: 7days after vaccination of Vi-DT(pooled)/ Typbar TCV®
Other outcomes:
Locations:
city: Banke
country: Nepal
facility: Nepalgunj medical college
state: City- Nepalgunj
city: Rautahat
country: Nepal
facility: B.P.Koirala Institute of Health Sciences
state: Dharan
city: Kavre
country: Nepal
facility: Dhulikhel Hospital
state: Dhulikhel
city: Kathmandu
country: Nepal
facility: Kanti Children's Hospital
state: Sukedhara
Study officials:
affiliation: Kanti Children's Hospital
name: Ganesh Kumar Rai, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.