Clinical trial NCT03527355: Safety, Reactogenicity and Immunogenicity of Vi-DT;Typhoid Conjugate Vaccine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Typhoid
Keywords: Typhoid
Vi-DT
Conjugate vaccine
First in human
New vaccine
Lead sponsor: International Vaccine Institute
Sponsor class: OTHER
Collaborators: name: SK Bioscience Co., Ltd.
name: Bill and Melinda Gates Foundation
First posted: 2018-05-17
Enrollment: 285
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants age 6-23 months
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety endpoints: solicited and unsolicited adverse events and serious adverse events
timeFrame: 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 outcomes:
measure: Immunogenicity Endpoints
timeFrame: At week 28, 4 weeks after the second vaccination
Other outcomes:
measure: Exploratory Endpoints
timeFrame: At week 4, 4 week after MMR vaccination
measure: Exploratory Endpoints
timeFrame: At week 28, 4 weeks after the second vaccination and at week 96 after the booster dose in selected group.
Locations:
city: Alabang
country: Philippines
facility: Research Institute for Tropical Medicine(RITM)
state: Muntinlupa City
Study officials:
affiliation: Research Institute for Tropical Medicine, Metro Manila, Philippines
name: Maria Rosario Capeding, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Capeding MR, Sil A, Tadesse BT, Saluja T, Teshome S, Alberto E, Kim DR, Park EL, Park JY, Yang JS, Chinaworapong S, Park J, Jo SK, Chon Y, Yang SY, Ryu JH, Cheong I, Shim KY, Lee Y, Kim H, Lynch JA, Kim JH, Excler JL, Wartel TA, Sahastrabuddhe S. Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study. EClinicalMedicine. 2020 Sep 9;27:100540. doi: 10.1016/j.eclinm.2020.100540. eCollection 2020 Oct.
citation: Capeding MR, Alberto E, Sil A, Saluja T, Teshome S, Kim DR, Park JY, Yang JS, Chinaworapong S, Park J, Jo SK, Chon Y, Yang SY, Ham DS, Ryu JH, Lynch J, Kim JH, Kim H, Excler JL, Wartel TA, Sahastrabuddhe S. Immunogenicity, safety and reactogenicity of a Phase II trial of Vi-DT typhoid conjugate vaccine in healthy Filipino infants and toddlers: A preliminary report. Vaccine. 2020 Jun 9;38(28):4476-4483. doi: 10.1016/j.vaccine.2019.09.074. Epub 2019 Oct 1.