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

Typhoid Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03933098
• Other study ID #: IVI T003
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 15, 2019
• Est. completion date: January 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 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1800
• Est. completion date: January 2021
• Est. primary completion date: September 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Typhoid
• Typhoid Fever

Intervention

Biological:
• Test Vaccine Vi-DT Typhoid conjugate
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
• Control Vaccine Typbar TCV®
Manufacturer: Bharat Biotech Ingredient: Purified Vi capsular polysaccharide of Salmonella Ty2 conjugated to tetanus toxoid protein Dose: 0.5 ml

Locations

Country	Name	City	State
Nepal	Nepalgunj medical college	Banke	City- Nepalgunj
Nepal	Kanti Children's Hospital	Kathmandu	Sukedhara
Nepal	Dhulikhel Hospital	Kavre	Dhulikhel
Nepal	B.P.Koirala Institute of Health Sciences	Rautahat	Dharan

Sponsors (2)

Lead Sponsor	Collaborator
International Vaccine Institute	SK Bioscience Co., Ltd.

Country where clinical trial is conducted

Nepal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seroconversion rate1	Defined as a 4-fold increase of serum anti-Vi IgG antibody titer	4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0)
Primary	Geometric Mean Titers (GMT)1	Measurement of the Geometric Mean Titers (GMT) following 4 weeks after vaccination of three lots of Vi-DT	4 weeks after vaccination of Vi-DT
Secondary	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®	4 weeks and 24 weeks after vaccination of Vi-DT(pooled)/ Typbar TCV®
Secondary	Seroconversion rate 2	Defined as a 4-fold increase of serum anti-Vi IgG antibody titer	24 weeks (168 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0).
Secondary	Seroconversion rate 3	Definded as a Seroconversion rates of anti-Vi IgG ELISA antibody titers after vaccination of three lots of Vi-DT.	4 weeks (28 days) after vaccination of Vi-DT(pooled)
Secondary	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	4 weeks (28 days) after vaccination of Vi-DT(pooled)
Secondary	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	4 weeks (28 days) after vaccination of MR compared to baseline (D0)
Secondary	Safety endpoints for solicited adverse events (reactogenicity)	Proportion of participants with local and systemic solicited adverse events	7days after vaccination of Vi-DT(pooled)/ Typbar TCV®