Safety and Immunogenicity of a Vi-DT Typhoid Conjugate Vaccine

Sponsor

International Vaccine Institute (Other)

Overall Status

Completed

CT.gov ID

NCT02645032

Collaborator

SK Chemicals Co., Ltd. (Industry)

144

Enrollment

Arms

8.7

Actual Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase I, Randomized, observer-blinded, age de-escalating study.

The study objectives are:

To evaluate the safety of 25 μg of Vi-DT typhoid conjugate vaccine administered at 0 and 4 weeks.
To assess the immunogenicity of 25 μg of Vi-DT typhoid conjugate vaccine administered at 0 and 4 weeks.
To compare the safety and immunogenicity of Vi-DT and Vi-Polysaccharide typhoid vaccines.

Condition or Disease	Intervention/Treatment	Phase
Typhoid	Biological: Vi-DT Biological: Typhim Vi® Biological: VAXIGRIP®	Phase 1

Detailed Description

This study will be carried out in healthy adults and children at a single site. Subjects will be stratified according to age.

The study procedure is as follows:

Visit 1 (day-1 to -7): Screen participants by medical history, physical examination and lab investigations. Collect blood for safety and immunogenicity assessments.

Visit 2 (day 0): Enroll, randomize and administer first dose of vaccine to eligible participants

Visit 3 (day 3): Assess participant safety by medical history and physical examination

Visit 4 (day 7): Record solicited adverse reaction 7 days post vaccination, and collect blood for safety lab assessments.

Visit 5 (day 28): Assess participant safety, collect blood for immunogenicity assessments, and administer second vaccine dose

Visit 6 (day 31): Participants safety will be assessed by medical history and physical examination

Visit 7 (day 35): Record solicited adverse reaction 7 days post second vaccination.

Visit 8 (day 56): Collect blood for immunogenicity assessments, assess participant safety, 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Laboratory personnel who analyzes immunogenicity at sponsor is also blinded.

Primary Purpose:

Prevention

Official Title:

A Randomized, Observer-Blinded, Phase I Study to Assess the Safety and Immunogenicity of Vi-DT Conjugate Vaccine Compared to Vi-Polysaccharide (Typhim Vi®, Sanofi Pasteur) Typhoid Vaccine in Healthy Filipino Adults and Children

Actual Study Start Date :

May 19, 2016

Actual Primary Completion Date :

Feb 9, 2017

Actual Study Completion Date :

Feb 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test group Two doses of Vi-DT (typhoid conjugate vaccine) will be administrated intramuscularly 4 weeks apart (Day 0 and Day 28).	Biological: Vi-DT Manufacturer: SK Chemicals Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial Other Names: Vi-DT typhoid conjugate vaccine
Active Comparator: Comparator group Biological/Vaccine: One dose of Typhim Vi® will be administrated intramuscularly at 1st dose (Day 0). One dose of VAXIGRIP® will be administrated intramuscularly at 2nd dose (Day 28).	Biological: Typhim Vi® Manufacturer: Sanofi Pasteur Ingredient: Purified Vi-polysaccharide Appearance: colourless liquid Dose: 0.5mL/vial Biological: VAXIGRIP® Dose: Single injection, participants 6-35 months of age will receive 0.25 ml (half a dose), participants 36 months of age and older will receive 0.5ml (full dose) *Participants less than 9 years of age, who have not been vaccinated for flu before, will receive a second dose of flu-vaccine after the last follow-up visit of last participant in their age cohort.

Arm

Intervention/Treatment

Experimental: Test group

Two doses of Vi-DT (typhoid conjugate vaccine) will be administrated intramuscularly 4 weeks apart (Day 0 and Day 28).

Biological: Vi-DT

Manufacturer: SK Chemicals Co., Ltd. Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid Dose: 0.5 mL/Vial

Other Names:

Vi-DT typhoid conjugate vaccine

Active Comparator: Comparator group

Biological/Vaccine: One dose of Typhim Vi® will be administrated intramuscularly at 1st dose (Day 0). One dose of VAXIGRIP® will be administrated intramuscularly at 2nd dose (Day 28).

Biological: Typhim Vi®

Manufacturer: Sanofi Pasteur Ingredient: Purified Vi-polysaccharide Appearance: colourless liquid Dose: 0.5mL/vial

Biological: VAXIGRIP®

Dose: Single injection, participants 6-35 months of age will receive 0.25 ml (half a dose), participants 36 months of age and older will receive 0.5ml (full dose) *Participants less than 9 years of age, who have not been vaccinated for flu before, will receive a second dose of flu-vaccine after the last follow-up visit of last participant in their age cohort.

Outcome Measures

Primary Outcome Measures

Safety endpoints for solicited adverse events (reactogenicity) and serious adverse events [4 weeks post first and second vaccination]
Proportion of participants with local and systemic solicited adverse events (reactogenicity) and Proportion of participant with Serious Adverse Events (SAEs)

Secondary Outcome Measures

Proportion of participants with sero-conversion [4 weeks post first and second injections of Vi-DT and one injection of Vipolysaccharide]
Defined as a four-fold rise in anti-Vi antibody titers compared to baseline measured by anti-Vi IgG ELISA and Serum Bactericidal Assay
Geometric Mean Titers (GMT) [4 weeks post first and second vaccination]
Measurement of the Geometric Mean Titers (GMT) following 4 weeks post first and second injections of Vi-DT and one injection of Vi-polysaccharide vaccine

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy male and female individual 2-45 years of age
Participants/Parents who have voluntarily given informed consent and/or assent.
Participants/Parents willing to commit complying with the study procedures of the investigator and available for the entire duration of study

Exclusion Criteria:

Participants concomitantly enrolled or scheduled to be enrolled in another trial
Acute illness, in particular infectious diseases or fever (axillary temperature > 38°C), with in three days prior to enrollment and vaccination.
Known history of allergy to vaccines or other medications
Known history of allergy to egg, chiken protein, neomycin and formaldehyde.
History of uncontrolled coagulopathy or blood disorders
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
Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the participant and interfere with the assessment of the trial objectives
Pregnancy & Lactation (female adults)
Female with child-bearing potential during the study period. i.e., sexually active and not practicing effective acceptable contraceptive method
Individuals who have previously received any vaccines against typhoid fever
Individuals already immunized with any licensed vaccine within 4 weeks prior to enrolment/vaccination (day 0) and expected to receive other licensed vaccines within 60 days following the first dose (day 0), except for tetanus toxoid vaccine
Individuals who have a previously ascertained or suspected disease caused by S. typhi.
Individuals who have had household contact with/and or intimate exposure to an individual with laboratory-confirmed S. typhi
History of alcohol or substance abuse
Subject planning to move from the study area before the end of study period