Safety, Reactogenicity and Immunogenicity of Vi-DT;Typhoid Conjugate Vaccine

Typhoid Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03527355
• Other study ID #: IVI T002
• Status: Completed
• Phase: Phase 2
• Start date: April 18, 2018
• Est. completion date: January 19, 2021

Study information

• Verified date: April 2020
• Source: International Vaccine Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 285
• Est. completion date: January 19, 2021
• Est. primary completion date: July 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 23 Months

Eligibility

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

Related Conditions & MeSH terms

• Typhoid
• Typhoid Fever

Intervention

Biological:
• Vi-DT
Manufacturer: SK Bioscience Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial
• FluQuadri™
Manufacturer: Sanofi Pasteur Dose: 0.25 ml *Participants who have not been vaccinated for flu before, will receive a second dose of flu-vaccine after unblinding.

Other:
• 0.9% sodium chloride isotonic solution
Manufacture: Euro-Med Inc. Dose: 0.5 mL

Locations

Country	Name	City	State
Philippines	Research Institute for Tropical Medicine(RITM)	Alabang	Muntinlupa City

Sponsors (3)

Lead Sponsor	Collaborator
International Vaccine Institute	Bill and Melinda Gates Foundation, SK Bioscience Co., Ltd.

Country where clinical trial is conducted

Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Endpoints	Seroconversion rates of Measles, Mumps and Rubella will be determined 4 week after MMR vaccination. Serum titers will be measured by routinely used commercially available ELISA kits. Kit-specific threshold of positivity will be used to determine specific seroconversion rates.	At week 4, 4 week after MMR vaccination
Other	Exploratory Endpoints	Serum bactericidal titers will be determined using in-house functional assay assessing the number of survived S. Typhi Ty2 strain colony on Luria-Bertani plate. Serum bactericidal titer is defined as the highest dilution of serum that gives 50% of inhibition of colony formation of S. Typhi.	At week 28, 4 weeks after the second vaccination and at week 96 after the booster dose in selected group.
Primary	Safety endpoints: solicited and unsolicited adverse events and serious adverse events	Frequency (percentage) of solicited local reactions at the injection site: Pain, tenderness, erythema/redness, swelling/induration and pruritus local; Frequency (percentage) of solicited systemic reactions: Fever, lethargy, irritability, vomiting, diarrhea, drowsiness, loss of appetite, persistent crying, rash and nasopharyngitis; Frequency (percentage) of unsolicited adverse events; Frequency (percentage) of serious adverse events	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	Immunogenicity Endpoints	Seroconversion rate of anti-Vi IgG by Geometric Mean Titers (GMT) will be measured 4 weeks after the second vaccination using an in-house ELISA assay using standardized reagents and reference serum. The level of the specific anti-Vi IgG in ELISA units for each serum sample is determined by comparison to a reference serum. The number of anti-Vi IgG positive sera will be used to calculate the seroconversion rates.	At week 28, 4 weeks after the second vaccination

External Links

•   A preliminary report